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Cited by 41Cardiovascular Function and Risk FactorsCardiomyopathy and Myosin StudiesCardiac Fibrosis and Remodeling

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Cardiovascular Function of Modern Pigs Does not Comply with Allometric Scaling Laws

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van Essen, Gerard J., te Lintel Hekkert, Maaike, Sorop, Oana, Heinonen, Ilkka, van der Velden, Jolanda, Merkus, Daphne, Duncker, Dirk J.·2018·Scientific Reports
DOI 10.1038/s41598-017-18775-zPMC PMC5768797
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Abstract

Growing concerns have been expressed regarding cardiovascular performance in modern farm pigs, which has been proposed as a critical factor contributing to the reduced adaptability of modern pigs to stress. Here we tested the hypothesis that cardiac dimensions and pump function in modern heavy farm pigs are disproportionally low for their body weight, and investigated potential underlying mechanisms. The results from the present study indeed demonstrate disproportionally low values for stroke volume and cardiac output in pigs with bodyweights over 150 kg. Importantly, these low values were not the result of impaired left ventricular (LV) systolic contractile function, but were due to a disproportionally small LV end-diastolic volume. The latter was associated with changes in determinants of LV passive stiffness, including (i) an increase in LV myocardial collagen, (ii) a shift from the compliant N2BA titin isoform towards the stiff N2B, and (iii) a marked elevation of aortic blood pressure. Taken together, these results demonstrate reduced pumping capacity of the hearts of heavy modern pigs, due to structural abnormalities in the LV myocardium.

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Figures

Figure 1 Relations between heart weight and body weight (panels a and b) and left ventricular weight and body weight (panels c and d). Absolute values of heart Heart weight (HW) and left ventricle weight (LVW), respectively, plotted to body weight (panels a and c). To linearize the formulas HW = 9.97 × BW0.78 and LVW = 6.00×BW0.78, the common logarithm was taken: log(HW or LVW) = log(a) + b.log(BW), with the predicted value of exponent b of 0.75 falling well within the 95% confidence limits (panels b and d). This indicates that HW and LVW scale proportionally with body weight according to the natural scaling laws.
Figure 1 Relations between heart weight and body weight (panels a and b) and left ventricular weight and body weight (panels c and d). Absolute values of heart Heart weight (HW) and left ventricle weight (LVW), respectively, plotted to body weight (panels a and c). To linearize the formulas HW = 9.97 × BW0.78 and LVW = 6.00×BW0.78, the common logarithm was taken: log(HW or LVW) = log(a) + b.log(BW), with the predicted value of exponent b of 0.75 falling well within the 95% confidence limits (panels b and d). This indicates that HW and LVW scale proportionally with body weight according to the natural scaling laws.CC BY · PubMed Central
Figure 2 Relations between cardiac output and body weight (panels a and b) and stroke volume and body weight (panels c and d). Absolute values of cardiac output (CO) and stroke volume (SV), respectively, plotted to body weight (panels a and c). To linearize the formulas CO = 0.55 × BW0.52 and SV = 3.51·BW0.66, the common logarithm was taken: log(CO or SV) = log(a) + b.log(BW), with the predicted exponents b of 0.75 for CO, and 1.00 for SV falling outside the 95% confidence interval (panels b and d). This indicates that CO and SV failed to scale proportionally with body weight according to the natural scaling laws.
Figure 2 Relations between cardiac output and body weight (panels a and b) and stroke volume and body weight (panels c and d). Absolute values of cardiac output (CO) and stroke volume (SV), respectively, plotted to body weight (panels a and c). To linearize the formulas CO = 0.55 × BW0.52 and SV = 3.51·BW0.66, the common logarithm was taken: log(CO or SV) = log(a) + b.log(BW), with the predicted exponents b of 0.75 for CO, and 1.00 for SV falling outside the 95% confidence interval (panels b and d). This indicates that CO and SV failed to scale proportionally with body weight according to the natural scaling laws.CC BY · PubMed Central
Figure 3 Relations between LV end-diastolic lumen area and body weight (panels b and d) and LV end-diastolic lumen volume and body weight (panels c and d). Absolute levels of left ventricular end-diastolic lumen area (LVEDA) and LV end-diastolic lumen volume (LVEDV), respectively, plotted to body weight (panels a and c). To linearize the formulas LVEDA = 418·BW0.37 and LVEDV = 4.24·BW0.78, the common logarithm was taken: log(LVEDA or LVEDV) = log(a) + b.log(BW), with the predicted exponents b of 0.67 for LVEDA, and 1.00 for LVEDV falling outside the 95% confidence interval (panels b and d). This indicates that LVEDA and LVEDV failed to scale proportionally with body weight according to the natural scaling laws.
Figure 3 Relations between LV end-diastolic lumen area and body weight (panels b and d) and LV end-diastolic lumen volume and body weight (panels c and d). Absolute levels of left ventricular end-diastolic lumen area (LVEDA) and LV end-diastolic lumen volume (LVEDV), respectively, plotted to body weight (panels a and c). To linearize the formulas LVEDA = 418·BW0.37 and LVEDV = 4.24·BW0.78, the common logarithm was taken: log(LVEDA or LVEDV) = log(a) + b.log(BW), with the predicted exponents b of 0.67 for LVEDA, and 1.00 for LVEDV falling outside the 95% confidence interval (panels b and d). This indicates that LVEDA and LVEDV failed to scale proportionally with body weight according to the natural scaling laws.CC BY · PubMed Central
Figure 4 Myocardial collagen content in an animal in each of the three weight categories. (a) Collagen staining (picrosirius red) of LV myocardial sections. Upper panels show slides using light microscopy, while lower panels show same tissue slides using a linear polarization filter. (b) Bar graph showing amount of collagen as percentage of myocardium area. Total collagen and collagen type I (thick fibers) are increased in the highest weight category. Measured in a subset within each group (n = 4, n = 5 and n = 4 respectively for each group); Data are presented as individual animal data points and as mean ± s.e.m.; *P < 0.05 vs < 75 kg-group; †P < 0.05 vs 75–150 kg-group (by One-Way ANOVA followed by SNK post-hoc testing).
Figure 4 Myocardial collagen content in an animal in each of the three weight categories. (a) Collagen staining (picrosirius red) of LV myocardial sections. Upper panels show slides using light microscopy, while lower panels show same tissue slides using a linear polarization filter. (b) Bar graph showing amount of collagen as percentage of myocardium area. Total collagen and collagen type I (thick fibers) are increased in the highest weight category. Measured in a subset within each group (n = 4, n = 5 and n = 4 respectively for each group); Data are presented as individual animal data points and as mean ± s.e.m.; *P < 0.05 vs < 75 kg-group; †P < 0.05 vs 75–150 kg-group (by One-Way ANOVA followed by SNK post-hoc testing).CC BY · PubMed Central
Figure 5 Titin isoform content in an animal in each of the three weight categories. (a) Gels showing titin isoform staining using SYPRO Ruby protein staining. Each example is from a different gel and gels are cropped. (Full length gels are included in Supplementary Information S4). The grayscale of the 75–150 kg-group gel is adjusted to generate equal appearance of the three gels. (b) Bar graph showing titin ratio (N2BA/N2B isoform). Ratio is decreased in the highest weight category, indicating a shift from the compliant N2BA titin isoform towards the stiff N2B titin isoform. Measured in a subset within each group (n = 7, n = 7 and n = 4, respectively, for each group); Data are presented as individual animal data points and as mean ± s.e.m.; *P < 0.05 vs < 75 kg-group; †P < 0.05 vs 75–150 kg-group (by One-Way ANOVA followed by SNK post-hoc testing).
Figure 5 Titin isoform content in an animal in each of the three weight categories. (a) Gels showing titin isoform staining using SYPRO Ruby protein staining. Each example is from a different gel and gels are cropped. (Full length gels are included in Supplementary Information S4). The grayscale of the 75–150 kg-group gel is adjusted to generate equal appearance of the three gels. (b) Bar graph showing titin ratio (N2BA/N2B isoform). Ratio is decreased in the highest weight category, indicating a shift from the compliant N2BA titin isoform towards the stiff N2B titin isoform. Measured in a subset within each group (n = 7, n = 7 and n = 4, respectively, for each group); Data are presented as individual animal data points and as mean ± s.e.m.; *P < 0.05 vs < 75 kg-group; †P < 0.05 vs 75–150 kg-group (by One-Way ANOVA followed by SNK post-hoc testing).CC BY · PubMed Central

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Citations

Cites

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Metadata

Authors
van Essen, G. J., te Lintel Hekkert, M., Sorop, O., Heinonen, I., van der Velden, J., Merkus, D., & Duncker, D. J.
Affiliations
  • Erasmus MC (NL)
  • University of Turku (FI)
  • Netherlands Heart Institute (NL)
Corresponding author
Duncker, Dirk J.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-01-15
Volume
8
Issue
1
Pages
792-792
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-017-18775-z
PMC
PMC5768797
OpenAlex
W2783442741
Cited by
41
References
4
Citations by year
2025: 6 · 2024: 7 · 2023: 8 · 2022: 5 · 2021: 6 · 2020: 6 · 2019: 3
FWCI
2.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, cc-by)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
  • UTUPub (University of Turku) (submittedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
  • Foundation for Cardiovascular Research
  • European Commission (FP7-Health- 2010, 261409)
  • Sydäntutkimussäätiö
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
farm pigs, cardiovascular function, allometric scaling, stroke volume, cardiac output, left ventricular end-diastolic volume, myocardial collagen, titin isoforms, aortic pressure, heavy pigs, stress adaptability, cardiac pump function
MeSH terms
Animals, Blood Pressure, Body Weight, Collagen, Heart Ventricles, Myocardium, Swine, Ventricular Function, Left, Protein Isoforms, Connectin

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