The DOI matches its Crossref record; 224 of the 224 references it cites were found in a registry or an index; 3 of the 199 sources its claims cite were checked for support.
Small and large animal models in cardiac contraction research: Advantages and disadvantages
Open accessAbstract
The mammalian heart is responsible for not only pumping blood throughout the body but also adjusting this pumping activity quickly depending upon sudden changes in the metabolic demands of the body. For the most part, the human heart is capable of performing its duties without complications; however, throughout many decades of use, at some point this system encounters problems. Research into the heart's activities during healthy states and during adverse impacts that occur in disease states is necessary in order to strategize novel treatment options to ultimately prolong and improve patients' lives. Animal models are an important aspect of cardiac research where a variety of cardiac processes and therapeutic targets can be studied. However, there are differences between the heart of a human being and an animal and depending on the specific animal, these differences can become more pronounced and in certain cases limiting. There is no ideal animal model available for cardiac research, the use of each animal model is accompanied with its own set of advantages and disadvantages. In this review, we will discuss these advantages and disadvantages of commonly used laboratory animals including mouse, rat, rabbit, canine, swine, and sheep. Since the goal of cardiac research is to enhance our understanding of human health and disease and help improve clinical outcomes, we will also discuss the role of human cardiac tissue in cardiac research. This review will focus on the cardiac ventricular contractile and relaxation kinetics of humans and animal models in order to illustrate these differences.
Overview
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Written from the paper’s full text.
TL;DR
This review compares commonly used laboratory animals for cardiac contraction research and concludes that no single model perfectly mirrors the human heart. Larger species generally resemble human contractile and relaxation kinetics more closely, while small rodents offer speed, cost, and genetic tractability.
Key findings
- Heart size and body mass relate inversely to heart rate and directly to contractile kinetics: mice can beat up to ~800 bpm, elephants ~35 bpm, and ventricular kinetics are ~2–3× faster in rabbits and ~4–12× faster in mice/rats than in humans; canine, swine, and sheep are closer to human values.
- Molecular differences are substantial: small rodents predominantly express fast α-MHC (>94–100%), whereas human ventricles are mostly slow β-MHC (>90–95%); rabbit, canine, swine, and sheep predominantly express β-MHC. Titin N2BA:N2B ratios are ~0.4–1.2 in humans, ~0.05–0.25 in mice, ~0.06–0.1 in rats, ~0.6–1 in canines, ~1–1.5 in swine, and ~0.35–0.43 in sheep. SERCA handles ~90–92% of calcium removal in rodents versus ~76% in humans; rabbit ~70–74%, canine ~73%, sheep ~81.5%.
- Exercise reserve and force-frequency responses differ: humans increase heart rate ~140–170% with exercise, versus ~40–50% in rats, ~30–40% in mice, ~71–112% in rabbits, ~96–136% in canines, and ~128–219% in swine. Human trabeculae force rises ~81–168% from 0.5 to 2.5 Hz; rabbit ~120–200% (1–4 Hz), rat ~30–40% (4–8 Hz), mouse nearly flat (8–12 Hz), and sheep ~139–171% (0.5–2 Hz).
- Model trade-offs: mice/rats are cheap, fast, and genetically tractable but most distant from human contraction; rabbits are intermediate; canines are closest for electrophysiology, sino-atrial node, Purkinje fibers, and exercise but are costly and harder to approve; swine and sheep are strong large-animal preclinical models with high housing costs; human tissue is valuable but scarce and variable.
Methods
- Narrative review of published literature comparing mouse, rat, rabbit, canine, swine, sheep, and human myocardium, focused on ventricular contraction and relaxation kinetics.
- Synthesizes ex vivo isometric trabeculae data and in vivo pressure-volume/catheterization data, plus molecular and calcium-handling comparisons, with tables/figures normalizing parameters to human values.
- No primary experiments or systematic search/meta-analysis are described.
Limitations
- The paper states that no ideal animal model exists; each has advantages and disadvantages, and translation depends on the process studied and on how well the disease model recapitulates human disease progression (e.g., sudden aortic banding versus gradual human aortic stenosis).
- Human samples are limited and variable because of genetics, medications, diet, exercise, social habits, and disease severity; donor hearts often have underlying abnormalities, and ischemia, delayed freezing, LVAD-induced remodeling, and inotropic agents can confound results.
- Evident from the text: the review is narrative rather than systematic, and cross-species comparisons draw on heterogeneous studies with differing temperatures, stimulation frequencies, anesthesia, and sample sources, which can affect contractile measurements.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
100 Not checked yet · 90 Own interpretation · 25 No basis given · 5 Own result · 1 Partly supported · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“other studies which have shown a much higher extent of human cTnI phosphorylation (with un-phosphorylated group accounting for as low as ~2–10%)”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Disadvantages
What the sources say
- Partly supportedcites Kooij, et al., 2010 sourceExperimental — accuracy not yet measured
The Results section, “Phosphorylation of sarcomeric proteins and recombinant cTn complex” (page unavailable), reports high mono- and bis-phosphorylation of cTnI in human donor tissue, supporting the claim of extensive phosphorylation. It does not give an unphosphorylated fraction of ~2–10%; the Results section on cTn exchange gives percentages for bis-phosphorylation relative to donor tissue, not that fraction. (LLM, conf=0.84)
- Partly supportedcites van Dijk, et al., 2011 sourceExperimental — accuracy not yet measured
The cTnI phosphorylation results (Figure 3D; page not available in our copy) report a lower unphosphorylated fraction in donor hearts than in both HCM patient groups, supporting the comparison qualitatively. Our copy does not give a 2–10% unphosphorylated fraction, so it does not substantiate that numerical range. (LLM, conf=0.82)
- Supportedcites Wijnker, et al., 2013 source
The Results (page not provided) report that unphosphorylated cTnI averaged 1.8 ± 0.5% in three human donor hearts—approximately 2%, consistent with the claim's low-end figure and indicating extensive phosphorylation. The paper does not establish the 10% endpoint, but the claim says the fraction can be as low as approximately 2–10%, not that this study measured the full range. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Partly supported
None of the sources cited for this claim have been checked yet.
In the paper
“Just the daily housing fees of sheep, pigs, canines, and rabbits are approximately 80, 60, 90, and 30 times more expensive than mice, respectively (values based upon 2013 fees charged by The Ohio State University ULAR and assuming 5 mice per cage).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 6. Sheep Models > Disadvantages
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Most notably, sheep are much more expensive to purchase and maintain in animal facilities than small animal models.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 6. Sheep Models > Disadvantages
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“Successful cardiac transduction in large species requires surgical and catheter-based approaches that can preferentially target the heart”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Advantages
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“There are a variety of mouse and rat cardiac dysfunction and heart failure models available, each with its own advantages and disadvantages.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Advantages
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“diazoxide, an ATP sensitive potassium (KATP) channel opener, affects action potential duration (APD) of atria and ventricles of mouse and humans differently.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Advantages
What the sources say
- Not checked yetcites Fedorov, et al., 2011 source
- Not checked yetcites Glukhov, Fedorov, et al., 2010
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hearts of smaller species need to contract and relax more rapidly than larger species in order to maintain cardiac output at high heart rates.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 1. Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“AAV-9 has been shown to have superior cardiotropism than other serotypes in small rodents”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Advantages
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This model is particularly attractive as it can be established via a single injection without the need of surgical procedures.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Advantages
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“a nonsense T116G gene mutation in humans that causes a deficiency of phospholamban results in severe dilated cardiomyopathy in individuals homozygous for the mutation, requiring cardiac transplantation”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Advantages
What the sources say
- Not checked yetcites Haghighi, et al., 2003 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 21
- It may state two separate claims as one. 67
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Currently in our institution, human hearts are shared among several laboratories which study processes ranging from contraction at the myofilament level to cardiac excitation at the tissue level.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 7. Verification Using Human Tissue
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Note that while left ventricular pressure remains constant, contractile and relaxation kinetics scale with body weight and these kinetics approach those of humans as animal size increases.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 8. Conclusion
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Figure 2 shows various ex vivo (only mouse, rat, rabbit, canine, and human available) and in vivo (all species) contractile and relaxation parameters normalized to human values.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 8. Conclusion
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, there are differences between the heart of a human being and an animal and depending on the specific animal, these differences can become more pronounced and in certain cases limiting.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mouse and rat predominately express N2B titin and considerably lower N2BA titin isoform with N2BA:N2B ratio ranges of ~0.05–0.25 in mouse and ~0.06–0.1 in rat”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Disadvantages
What the sources say
- Not checked yetcites Cazorla, et al., 2000 source
- Not checked yetcites Neagoe, Opitz, Makarenko, & Linke, 2003
- Not checked yetcites Opitz & Linke, 2005
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“The phospholamban (PLB) knock-out mouse has enhanced cardiac contractility, without affecting life span”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Advantages
What the sources say
- Not checked yetcites Slack, et al., 2001 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These cases illustrate the differential response of mice and humans to genetic alterations and the limitations of genetic mouse models in studying human cardiovascular disease.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Advantages
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“the same concentration of diazoxide decreased mouse atria APD while it had no effect on human atria APD. The opposite was observed in the ventricles; diazoxide did not affect mouse ventricle APD while it slightly decreased human ventricle APD”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Advantages
What the sources say
- Not checked yetcites Fedorov, et al., 2011 source
- Not checked yetcites Glukhov, Fedorov, et al., 2010
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The mdx (dystrophin deficient) mouse model has a rather mild cardiomyopathy, mild limb-skeletal muscle dysfunction, and a normal life span, in contrast to human counterparts”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Advantages
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“a mouse model lacking both dystrophin and utrophin shows a much more severe phenotype, and a reduced lifespan”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Advantages
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Depending on the cardiovascular process being studied, the choice of animal model needs to be considered carefully since it affects experimental outcomes and whether findings of the study can be reasonably translated to humans.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 1. Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These studies highlight the limitations of directly translating pharmacological efficacy and toxicity of compounds from murines to humans, which is in addition to known differences in pharmacokinetics.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Advantages
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“lower doses of this compound result in right ventricular hypertrophy while higher dosage is required in order to induce right-sided heart failure”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Advantages
What the sources say
- Not checked yetcites Hessel, et al., 2006 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Table 1 shows the inverse relationship between body weight and heart rate while blood pressure remains relatively constant across various laboratory animals and humans.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 1. Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Small rodents are effective animal models with distinct advantages over larger animal models; however, as will be discussed next in detail, they have various limitations and disadvantages.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Advantages
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There is no ideal animal model available for cardiac research, the use of each animal model is accompanied with its own set of advantages and disadvantages.”
- Also stated in: § 1. Introduction · plain
“there is no perfect animal model of the human heart; each model has its own set of advantages and disadvantages.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > Abstract
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
- Also stated in: § 1. Introduction · plain
In the paper
“Mouse action potentials have a rapid repolarization and lack a prominent plateau phase which is found in human cardiomyocytes”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Disadvantages
What the sources say
- Not checked yetcites Nerbonne, 2004 source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“mouse models can be developed in a shorter period of time due to their short gestation age of ~18–21 days”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Advantages
What the sources say
- Not checked yetcites Ostergaard, et al., 2010
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The advantages of using these models are that they present significantly lower cost than larger animals, and the ability to investigate roles of various proteins and signaling pathways in progression of heart disease by combining these intervention models and genetically modified mouse models.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Advantages
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“ten weeks of pulmonary artery banding (PAB) is sufficient to induce hypertrophy in rabbits without signs and symptoms of heart failure in the right ventricle (Varian, et al., 2009) and with altered right atrial calcium handling (Gupta, et al., 2009).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Advantages
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“hypothyroidism (either by administration of propylthiouracil or thyroidectomy) in rats results in down-regulation of α-MHC and up-regulation of β-MHC (Rundell, et al., 2005; Tang, et al., 2005).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Disadvantages
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The kinetics of rabbit cardiac contraction and relaxation are approximately 2–3 times faster than humans yet more similar than smaller rodents where kinetics are as much as 4–12 times faster (See Table 2).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Advantages
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Following periods of rest after steady pacing, rabbits exhibit a post-rest decay where the first twitch tension is decreased while humans and rats show post-rest potentiation where the first twitch tension is increased as the rest periods are prolonged (Janssen, Lehnart, Prestle, & Hasenfuss, 1999; Maier, Bers, et al., 2000).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Disadvantages
What the sources say
- Not checked yetcites Janssen, et al., 1999 source
- Not checked yetcites Maier, Bers, et al., 2000
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Various methods for generating rabbit heart failure models are available including pacing-induced failure (D. Liu, Gao, Roy, Cornish, & Zucker, 2006), combined aortic insufficiency induced volume overload and aortic constriction induced pressure overload (Pogwizd, et al., 1999), and coronary ligation (Maurice, et al., 1999; D. C. White, et al., 2000).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Advantages
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The hearts of mouse and rat share many characteristics; however, there are differences even between these two species.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Disadvantages
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Many aspects of rabbit myocardium have greater similarity to humans than small rodents, making rabbits a model generally more closely representative of the human heart.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Advantages
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Rabbits have an in vivo heart rate range of 155–360 bpm (Gaustad, Rolim, & Wisloff, 2010; Jover, McGrath, & Ludbrook, 1987) which is still higher than humans (Flamm, et al., 1990; Stratton, et al., 1994) but significantly closer than mouse and rats”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Advantages
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Increasing the stimulation frequency in rabbit (from 1 Hz to 4 Hz) and human in vitro muscle preparations (from 0.5 Hz to 2.5 Hz) results increase in contractile force of about 120–200% and 81–168%, respectively”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Advantages
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“in mice the overall effect of this drug is a net negative inotropic response while in rats it is a net positive inotropic response (McCloskey, et al., 2002).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Disadvantages
What the sources say
- Not checked yetcites McCloskey, et al., 2002 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite a closer similarity to humans than mice/rats, differences between rabbit and human myocardium remain, which can result in a particular study or therapeutic intervention to have differential effects in rabbits and humans.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Disadvantages
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The time constant of SERCA dependent calcium decline alone (when NCX activity is blocked) is about 50 percent slower in humans than rabbits (approximately 600 ms in humans vs. 400 ms in rabbits) (Z. Su, et al., 2003).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Advantages
What the sources say
- Not checked yetcites Z. Su, et al., 2003
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Rabbit ventricular SERCA and NCX systems are responsible for removing 70–74% and 23–28% of calcium, respectively (Bassani, et al., 1994; Puglisi, Bassani, Bassani, Amin, & Bers, 1996). These values are again similar to the relative activities of SERCA (76%) and NCX (24%) in human ventricles (Piacentino, et al., 2003).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Advantages
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Note that stimulation frequency affects contractile and relaxation kinetics to some degree”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Advantages
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“humans have a much greater ability than rodents to increase their cardiac output during exercise by both heart rate and stroke volume mediated mechanisms.”
- Also stated in: § Disadvantages · plain
“In other words, the cardiac reserve of humans is much greater than rodents.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 2. Small Rodent Models (Mouse and Rat) > Disadvantages
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: A mouse typically can increase cardiac output by no more than one-third, while highly trained humans can increase it up to 10-fold.
- Also stated in: § Disadvantages · plain
None of the sources cited for this claim have been checked yet.
In the paper
“there is a high degree of resemblance between human and canine sino-atrial (SA) node activity and structure (Review: (Fedorov, Glukhov, & Chang, 2012)), purkinje fiber distribution, and activation sequence (Allison, et al., 2007; Hamlin, 2007).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Advantages
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“although this heart rate reserve (and consequently cardiac output reserve) is more than reserves of mice (~30–40%) and rats (~40–50%), it is still less than the reserve (~140–170%) available in humans (Flamm, et al., 1990; Stratton, et al., 1994).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Disadvantages
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This observation was attributed to the running behavior of rabbits in the wild (Meng & Pierce, 1990).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Disadvantages
What the sources say
- Not checked yetcites Meng & Pierce, 1990
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“One of these lines is the Golden Retriever Muscular Dystrophy (Cooper, et al., 1988) which develops cardiomyopathy with features that closely resemble those of affected humans (Moise, et al., 1991; Valentine, Cooper, de Lahunta, O'Quinn, & Blue, 1988; Valentine, Cummings, & Cooper, 1989) and is considered to better represent cardiac involvement in human DMD than their mouse mdx counterparts (Nakam”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Advantages
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“the relative contributions of SERCA and NCX to calcium removal in canine myocardium are 73% and 27% (Bers, 2001) and in human myocardium are estimated to be 76% and 24% (Piacentino, et al., 2003), respectively.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Advantages
What the sources say
- Not checked yetcites Bers, 2001
- Not checked yetcites Piacentino, et al., 2003 source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The rabbit heart shares many similarities to that of human although some variations exist.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Disadvantages
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“it is proposed that the “effective size” of the heart (third root of heart weight divided by spiral wave rotation period) determines ventricular fibrillation pattern. Based upon this analysis, it is argued that rabbits have a closer effective size to humans and hence more similar ventricular fibrillation patterns than either canines or pigs (Panfilov, 2006).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Advantages
What the sources say
- Not checked yetcites Panfilov, 2006 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, even though rabbit and human calcium handling mechanisms are more closely related than those of rat, this particular phenomenon in humans phenotypically more closely resembles that of the rat.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Disadvantages
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The loss of dystrophin gene product has a profound impact on human hearts while mouse myocardium is only minimally affected.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Advantages
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Both compliant N2BA and stiff N2B isoforms are expressed in canines (N2BA:N2B ratio of ~ 0.6–1) and humans (N2BA:N2B ratio of ~0.4–1.2) (Bell, et al., 2000; Cazorla, et al., 2000; Jaber, et al., 2008; Makarenko, et al., 2004; Nagueh, et al., 2004).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Advantages
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The action potential duration of canine is only a little bit shorter than that of humans, much more comparable than the animal models discussed previously (canine APD90: ~ 219 ms, human APD90: ~290 ms both measured in right ventricular papillary muscles at cycle length of 1000 ms and 37 °C) (Szel et al. 2011).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Advantages
What the sources say
- Not checked yetcites Szel et al. 2011 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“We must point out that this particular study was performed at sub-physiological temperature of 30 °C.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Advantages
What the sources say
- Not checked yetcites Taylor, et al., 2004 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“This reflects an increase of approximately 96–136% which is close-lower than the 140–170% increase in heart rate observed in humans (Flamm, et al., 1990; Stratton, et al., 1994).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Advantages
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the resting heart rate of a rabbit is considerably higher than humans; rabbit resting heart rate is near the upper limit of human heart rate even during exercise conditions.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Disadvantages
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The same report also showed that the canine SERCA activity is most comparable to humans, followed by rabbits and then mice.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Advantages
What the sources say
- Not checked yetcites Z. Su, et al., 2003
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This has largely been attributed to changes in sarcoplasmic reticulum calcium content during rest periods where rabbits’ and humans’ are decreased and increased, respectively (Maier, Bers, et al., 2000; Pieske, et al., 1999).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Disadvantages
What the sources say
- Not checked yetcites Maier, Bers, et al., 2000
- Not checked yetcites Pieske, et al., 1999 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, rabbits are an attractive model in cardiac research, balancing the increased cost when compared to mice and rats with a generally closer biological resemblance to human.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 3. Rabbit Models > Disadvantages
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Rabbits cost less to acquire and house than larger animal models such as canine and sheep.
- Rests on an assumption: Rabbits cost more to acquire and house than mice and rats.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Note that canine’s heart rate is faster than human’s during both rest and exercise conditions but closer than the previous species discussed.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Advantages
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Spontaneous occurring mutations in various canines resulting in lack of dystrophin have been identified and canine muscular dystrophy lines are established.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Advantages
What the sources say
- Not checked yetcites Cooper, et al., 1988 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As discussed for other large animal models, these techniques are not as simple as the intraperitoneal and intravenous techniques available in small rodents.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 5. Swine Models > Advantages
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Swine hearts have in vivo contractile and relaxation kinetics that are slightly faster than humans but much more similar than either small rodents or rabbits (Table 5).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 5. Swine Models > Advantages
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In one study by Yue et al. jugular vein injected AAV-9 in neonatal dogs while successfully transduced skeletal tissue, it failed to do so with cardiac muscle (Yue, et al., 2008).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Disadvantages
What the sources say
- Not checked yetcites Yue, et al., 2008 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Canine hearts are typically transduced via methods that specifically target the myocardium such as direct intramyocardial (Pepe, et al., 2010) and percutaneous transendocardial injections (Bish, Sleeper, et al., 2008) which are technically more challenging than simple IP and IV methods.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Disadvantages
What the sources say
- Not checked yetcites Pepe, et al., 2010 source
- Not checked yetcites Bish, Sleeper, et al., 2008
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“while the resting heart rates are just slightly higher than humans; the exercise heart rates are moderately higher than achievable in humans.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 5. Swine Models > Advantages
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These characteristics make canine and human myocardium behave similarly in response to exercise, making the canine generally a good model for exercise studies in cardiovascular research.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Advantages
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Other differences include small or lack of transient outward current (Ito) in swine (Lacroix, et al., 2002; G. R. Li, et al., 2003; Schultz, et al., 2007) and purkinje fiber distribution (Hamlin, 2007).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 5. Swine Models > Disadvantages
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“these genetic models have a valid role in cardiovascular research and can in most cases significantly better resemble human disease than small rodents.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Disadvantages
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Heart failure can be induced in swine by a variety of methods such as rapid pacing (Lacroix, et al., 2002) and myocardial infarction (Pleger, et al., 2011).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 5. Swine Models > Advantages
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“one of these reports (Chung, et al., 2011) concluded that not only swine expressed more N2BA than humans, but additionally the N2BA:N2B ratio of this animal model was more similar to dilated human cardiomyopathy, a condition were N2BA expression is upregulated (Makarenko, et al., 2004; Nagueh, et al., 2004).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 5. Swine Models > Disadvantages
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The rationale for pursuing these studies in canine becomes more convincing if prior studies in small rodents have already established the role of a particular gene, process, or phenomenon in cardiovascular health and disease.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Disadvantages
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Such differences include resting and exercise heart rates (see above), kinetics of Ito current inactivation, its recovery, and molecular size of its corresponding ion channels, sensitivity to flecanide (Akar, et al., 2004), and transmural epicardial:endocardial expression levels of HERG ion channel (Szabo, et al., 2005).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Disadvantages
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Some of these models include sudden cardiac death (review: (Billman, 2006)), rapid pacing induced heart failure (Recchia, et al., 1998; Sabbah, et al., 1991), repeated microembolization induced chronic heart failure (Sabbah, et al., 1991), gradual aortic constriction induced left-ventricular pressure-overload (Koide, et al., 1997).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 4. Canine Models > Advantages
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This issue can be addressed by collaboration between multiple laboratories in order to use these samples efficiently.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 7. Verification Using Human Tissue
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: Human samples are available only in limited quantities.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Sheep have a resting heart rate which is slightly higher than humans (See Table 1).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 6. Sheep Models > Advantages
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Another limitation is the need for techniques for transduction of myocardial tissue with AAV vectors (see above) as compared to intraperitoneal and intravenous injections which are feasible in small rodents.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 6. Sheep Models > Disadvantages
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Small rodents can be used to perform proof-of-principle experiments rapidly and cost-efficiently.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 7. Verification Using Human Tissue
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Despite the preservation and conservation of many aspect of the cardiovascular system during evolution of humans and commonly used laboratory animal models, various differences exist that must be considered.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 8. Conclusion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We believe that an approach that uses multiple animal models with verification using human myocardium is essential in advancing research in the cardiovascular field.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 7. Verification Using Human Tissue
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both small and large animal models have specific strengths and weaknesses, and all of the animal models discussed in this manuscript have an important role in cardiovascular research.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 8. Conclusion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The most common cause of non-congenital aortic constriction is calcification of aortic valve which is a gradual progressive and not sudden process resulting in progressive cardiac hypertrophy and heart failure (Dweck, Boon, & Newby, 2012; Nishimura, 2002).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 8. Conclusion
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, the use of human tissues, if available, can shed further light onto translational applications for human patients.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 8. Conclusion
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“On the other hand, if the objective of the study is to understand alterations in contractile and relaxation kinetics in heart failure, any of the large animal models will be appropriate, and the choice may be more dependent on economic or logistical factors.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 7. Verification Using Human Tissue
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“both sheep and human hearts have a positive force-frequency relationship.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 6. Sheep Models > Advantages
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These devices can induce some changes and reverse-remodeling in the myocardium (Ambardekar & Buttrick, 2011) which can further complicate analysis of results obtained from failing human samples.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 7. Verification Using Human Tissue
What the sources say
- Not checked yetcites Ambardekar & Buttrick, 2011
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Since the ultimate goal of biomedical research is to address human health and disease, experimental verification of potential treatment strategies or quantitative verification of novel pharmacological compounds in actual human tissue would further aid in moving treatments to clinical trials with minimal risk to the patient.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 7. Verification Using Human Tissue
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
None of the sources cited for this claim have been checked yet.
In the paper
“Sheep and human left ventricles express both major titin isoforms in considerable amounts with N2BA:N2B ratios of ~0.35–0.43 and ~0.4–1.2, respectively (Cazorla, et al., 2000; Kruger & Linke, 2006; Makarenko, et al., 2004; Nagueh, et al., 2004; Neagoe, et al., 2003).”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 6. Sheep Models > Advantages
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, studies in cardiovascular system should not rely on a single animal model to address all questions.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 8. Conclusion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whether these donor samples can be used as control is dependent on the objective of the study.”
§ Small and Large Animal Models in Cardiac Contraction Research: Advantages and Disadvantages > 7. Verification Using Human Tissue
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
The basic principles of cardiac excitation and contraction are relatively conserved across the species discussed.
“The basic principles of cardiac excitation and contraction in all of the species discussed in this review are relatively conserved.”
The paper relies on this without support.
The cardiovascular system of each animal evolved differently to meet the demands of that species.
“the cardiovascular system of each animal has evolved differently in order to meet the demands of that species.”
The paper relies on this without support.
Small rodents are easier to handle and house, have shorter gestation, and lower maintenance cost than larger animal models.
“Small rodents are easier to handle and house, have a shorter gestation time, and have lower maintenance cost than larger animal models.”
The paper relies on this without support.
Cardiac excitation, contraction, and relaxation of small rodents and humans share many similarities, and both express proteins with similar functions and roles.
“Cardiac excitation, contraction, and relaxation of small rodents and humans share many similarities and both groups express proteins with similar functions and roles.”
The paper relies on this without support.
The closer the heart or body weight of an animal model is to human, the more similar its heart is to human.
“As a simple rule, the closer the heart or body weight of the animal model to human; the more similar are the hearts.”
The paper relies on this without support.
Human cardiac tissue samples are available in limited quantities and exhibit great variability.
“These samples are however available in very limited quantities, and exhibit great variability due to differences in factors such as genetics, medications, diets, social habits, and diseases.”
The paper relies on this without support.
There is a need for a suitable animal model where cardiovascular physiology and disease can be studied efficiently and reliably with potential translational applicability to humans.
“There thus exists a need to have a suitable animal model where cardiovascular physiology and disease can be studied efficiently and reliably with potential translational applicability to humans.”
The paper relies on this without support.
A mouse typically can increase cardiac output by no more than one-third, while highly trained humans can increase it up to 10-fold.
“Where a mouse can increase its cardiac output by typically no more than one-third, humans can increase cardiac output as high as 10-fold in highly trained individuals.”
The paper relies on this without support.
Rabbits cost less to acquire and house than larger animal models such as canine and sheep.
“the cost of acquiring and housing rabbits is still significantly much lower which makes them an attractive alternative to larger animal models in cardiac research from an economic/logistic perspective.”
The paper relies on this without support.
Rabbits cost more to acquire and house than mice and rats.
“One of the major disadvantages of using rabbits is the cost associated with acquiring and housing them as compared to mice and rats.”
The paper relies on this without support.
Rabbits are cheaper than larger animal models including canine, pig, and sheep.
“rabbits are still cheaper than larger animal models including canine, pig, and sheep.”
The paper relies on this without support.
Human population heterogeneity is not reflected in inbred laboratory mouse, rat, or rabbit strains.
“the human population is heterogeneous with slight genetic variations; a property which is not reflected in the inbred laboratory mouse, rat, or rabbit strains.”
The paper relies on this without support.
Housing and maintenance of canine models is considerably more expensive than small rodents and rabbits.
“The housing and maintenance of canine models is considerably more expensive than small rodents and rabbits”
The paper relies on this without support.
Obtaining necessary approval for performing experiments in canines is generally difficult.
“it is generally difficult to obtain such approval for using canines as an animal model.”
The paper relies on this without support.
Even if canine use is justified and approval obtained, the number of animals that can be used can be limited.
“even if the use of canines is justified and the appropriate approval is obtained, the number of animals that can be used can be limited.”
The paper relies on this without support.
Swine have relatively high cost of housing and maintenance.
“Swine, typical of large animal models, have a relatively high cost of associated with housing and maintenance.”
The paper relies on this without support.
The time and cost associated with development of genetic swine models is a disadvantage compared with genetic mice models, which can be developed more rapidly and with lower cost.
“The time and cost associated with development of genetic swine models is a disadvantage when compared to genetic mice models which can be developed more rapidly and with lower cost.”
The paper relies on this without support.
Canines are highly similar to humans in the sino-atrial node and Purkinje fibers.
“For example, if the focus of the study is on sino-atrial node or purkinje fibers, it is recommended that canines be used due to the high degree of similarity that they share in these aspects with humans.”
The paper relies on this without support.
Approval for experiments on canines is often harder to obtain.
“due to the often greater difficulty associated with obtaining approval for performing experiments on canines.”
The paper relies on this without support.
The hearts of larger species and humans are inherently different.
“Nonetheless, even the hearts of these larger species and humans are inherently different.”
The paper relies on this without support.
Human myocardium for ex vivo analysis usually comes from rejected donor hearts or end-stage failing hearts donated after transplantation.
“Human myocardium suitable for ex vivo analysis can be typically obtained from 1) rejected donor hearts that were not suitable for cardiac transplantation or 2) end-stage failing hearts that were donated after the patient received cardiac transplantation.”
The paper relies on this without support.
Heart failure patients eligible for transplantation undergo tests and appointments that record information such as ejection fraction and medication compliance.
“Typically, heart failure patients who are eligible for transplantation undergo a battery of tests and regular physician appointments where information ranging from ejection fraction to medication compliance is recorded.”
The paper relies on this without support.
Most donor hearts have anatomical or acquired abnormalities that excluded them from transplantation.
“In most cases, such donor hearts have some underlying anatomical and/or acquired abnormalities (such as coronary artery disease, low ejection fraction, and/or advanced age) that excluded them for cardiac transplantation.”
The paper relies on this without support.
In some cases, inotropic agents are used to maintain organ perfusion during procurement.
“Furthermore, in some cases inotropic agents are used in order to maintain proper organ perfusion during the organ procurement process”
The paper relies on this without support.
Inotropic agents can alter post-translational modifications of cardiomyocyte proteins or, with extended use, protein expression levels.
“and the use of such agents can cause alterations in post-translational modifications of cardiomyocyte proteins, or when given for extended periods of time, modify protein expression levels.”
The paper relies on this without support.
Documentation of inotropic agent use is often unavailable to researchers or omitted at publication.
“Unfortunately, documentation of the use of such agents is not always readily available to researchers, and/or omitted at the time of publication.”
The paper relies on this without support.
Ischemia can occur during excision of the heart from the thoracic cavity in both rejected donor and end-stage failing hearts.
“One concern, common to both rejected donor and end-stage failing hearts, is that ischemia can happen during excision of the heart from the thoracic cavity.”
The paper relies on this without support.
Ischemia can affect myocardial tissue.
“Such ischemia can affect the myocardial tissue”
The paper relies on this without support.
Animal heart samples can be flash frozen quickly, sometimes within seconds.
“Heart samples from animal models can be quickly (if necessary within seconds) be flash frozen.”
The paper relies on this without support.
Quick freezing is usually impractical for donated human hearts, and freezing or placing on ice may take minutes to hours.
“However, in most settings such quick freezing is not practical for donated human hearts and in most cases it might take several minutes or even hours to freeze tissues or at least place on ice.”
The paper relies on this without support.
Delays in freezing human heart samples will hinder studies of post-translational modifications because such processes can occur and reverse within minutes.
“Such delays will become problematic if the goal of the study is to determine the post-translational modifications of proteins, as several of these process can occur, and reverse, in minutes.”
The paper relies on this without support.
Human samples are available only in limited quantities.
“One common limitation of both groups is that these human samples are available in limited quantities.”
The paper relies on this without support.
Pressure-overload in animal models is typically induced suddenly by placing a band on the aorta.
“Typically, such pressure-overload in animal models is induced suddenly with placing of a band over some part of the aorta.”
The paper relies on this without support.
Aortic constriction is used to induce hypertrophy and heart failure in small and large animal models.
“For example, consider aortic constriction that is used to induce hypertrophy and heart failure in both small and large animal models.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Rodent models are widely used in cardiovascular research due to their easy handling and housing, short gestation time, low maintenance costs, and more importantly ability for genetic manipulation.”
From Cardiovascular disease models: A game changing paradigm in drug discovery and screening (2019) · cites this paper as [84]
In the citing paper
“However, the main disadvantage of these small animal models (i.e. mice, rats, rabbits, and cats) is the relevance of the obtained results to humans due to the distinct physiological differences between these species and humans [84–86].”
From Cardiovascular disease models: A game changing paradigm in drug discovery and screening (2019) · cites this paper as [84]
In the citing paper
“infarct size in porcine models can be precisely predicted [84]”
From Cardiovascular disease models: A game changing paradigm in drug discovery and screening (2019) · cites this paper as [84]
In the citing paper
“Current animal models, including genetically modified ones for CVDs, are incapable of fully recapitulating human physiology and pathophysiology, and thus imprecisely predict the biology and mechanisms involved in human cardiac dysfunctions [84].”
From Cardiovascular disease models: A game changing paradigm in drug discovery and screening (2019) · cites this paper as [84]
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Metadata
- Authors
- Milani-Nejad, N., & Janssen, P. M. L.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Janssen, Paul M.L.
- ORCID
- Janssen, Paul M.L.
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 141
- Issue
- 3
- Pages
- 235-249
- ISSN
- 0163-7258 (ISSN-L)
- PMC
- PMC3947198
- OpenAlex
- W1966140207
- Cited by
- 484
- References
- 224
- Citations by year
- 2026: 37 · 2025: 48 · 2024: 42 · 2023: 51 · 2022: 56 · 2021: 51 · 2020: 53 · 2019: 40 · 2018: 39 · 2017: 22 · 2016: 17 · 2015: 21 · 2014: 7
- FWCI
- 10.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL113084, RC1HL099538)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- cardiac contraction, species differences, mice, rats, rabbits, canine, pigs, sheep, human cardiac tissue, cardiac hypertrophy
- MeSH terms
- Animals, Disease Models, Animal, Heart Diseases, Heart Ventricles, Humans, Myocardial Contraction, Species Specificity, Ventricular Function, Models, Animal
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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