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Cited by 94Cardiac Fibrosis and RemodelingCardiovascular Function and Risk FactorsCardiomyopathy and Myosin Studies

Left Ventricular Performance and Remodeling in Rabbits After Myocardial Infarction: Effects of a Thyroid Hormone Analogue

Mahaffey, Kenneth W., Raya, Thomas E., Pennock, Gregory D., Morkin, Eugene, Goldman, Steven·1995·Circulation
DOI 10.1161/01.cir.91.3.794
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Abstract

Background Because the rat postinfarction model differs from human heart failure with respect to the composition of myosin heavy chain (MHC) isoforms and other contractile proteins, alternative animal models are needed for the development of new treatments for human heart failure. The purpose of this study was threefold: (1) to test the feasibility of using the V 3(β,β) rabbit postinfarction model for the study of heart failure by characterizing the effects of chronic coronary artery occlusion on the left ventricle; (2) to determine whether the thyroid hormone analogue 3,5-diiodothyropropionic acid (DITPA) produces improvements in left ventricular function; and (3) to determine the effects of myocardial infarction and treatment with DITPA on MHC protein isoforms. Methods and Results Male New Zealand White rabbits underwent proximal circumflex coronary artery ligation. After infarction, rabbits were treated with DITPA (3.75 mg/kg body wt) or placebo for 21 days and then underwent conscious and open-chest hemodynamic studies. In separate groups of rabbits, β- and α-MHC isoforms were separated, and relative proportions were measured using gradient sodium dodecyl sulfate–polyacrylamide gel electrophoresis and laser densitometry. Infarction resulted in increased left ventricular end-diastolic pressure and prolonged left ventricular relaxation (τ) (P=.001 for both variables). Postinfarction treatment with DITPA decreased left ventricular end-diastolic pressure and τ (P=.002 and P=.001, respectively) and increased maximum positive and negative dP/dt (P=.002 and P=.016, respectively). Infarcted rabbits treated with DITPA had no significant changes in heart rate or left ventricular systolic pressure compared with untreated rabbits with infarction. There were no significant differences in heart rate, positive dP/dt, peak systolic pressure, or τ between sham-operated rabbits and sham-operated rabbits treated with DITPA. Although infarction resulted in increased left ventricular diameter, there were no effects of DITPA on left ventricular remodeling. Neither myocardial infarction nor treatment with DITPA altered the ratio of MHC isoforms. Conclusions Rabbits that survive occlusion of the circumflex artery will develop myocardial dysfunction and left ventricular remodeling. Therapy with DITPA, a thyroid hormone analogue, produces improvement in ventricular performance and reduces end-diastolic pressure. The hemodynamic effects of DITPA were not associated with alterations of MHC isoforms. Whether DITPA represents the prototype of a previously undescribed class of agents for the treatment of heart failure will need to be determined by clinical trials.

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  • Myocardial function in intact rabbits can be assessed with established in vivo quantitative and imaging techniques such as echocardiography, hemodynamic catheterization, electrocardiography, and cardiac MRI.

    “various in vivo quantitative and imaging techniques such as echocardiography (Pogwizd, Qi, Yuan, Samarel, & Bers, 1999), hemodynamic cardiac catheterization (Mahaffey, Raya, Pennock, Morkin, & Goldman, 1995; A. S. Shah, et al., 2000), electrocardiography (Pogwizd, et al., 1999), and cardiac magnetic resonance imaging (Jung, et al., 2012) are well established and are routinely performed in rabbits.”

    From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Mahaffey, et al., 1995

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Authors
Mahaffey, K. W., Raya, T. E., Pennock, G. D., Morkin, E., & Goldman, S.
Affiliations
University of Arizona (US)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
1995-02
Volume
91
Issue
3
Pages
794-801
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/01.cir.91.3.794
OpenAlex
W2010157062
Cited by
94
References
26
Citations by year
2025: 1 · 2020: 1 · 2019: 1 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 3
FWCI
4.20
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01hl048163-02, 5p01hl020984-21)
  • National Heart, Lung, and Blood Institute (R01 HL-48163, HL-20984)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
Keywords
myocardial infarction, left ventricular remodeling, left ventricular function, thyroid hormone analogs, myosin heavy chain isoforms, beta-myosin heavy chain, alpha-myosin heavy chain, heart failure model, coronary artery occlusion, ventricular relaxation, hemodynamics, rabbit model
MeSH terms
Animals, Diiodothyronines, Male, Myocardial Infarction, Myosins, Propionates, Rabbits, Ventricular Function, Left

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