Impairment of Diastolic Function by Lack of Frequency-Dependent Myofilament Desensitizationin Rabbit Right Ventricular Hypertrophy
Open accessAbstract
Background— Ventricular hypertrophy is a physiological response to pressure overload that, if left untreated, can ultimately result in ventricular dysfunction, including diastolic dysfunction. The aim of this study was to test the hypothesis that frequency-dependent myofilament desensitization, a physiological response of healthy myocardium, is altered in hypertrophied myocardium. Methods and Results— New Zealand white rabbits underwent a pulmonary artery banding procedure to induce pressure overload. After 10 weeks, the animals were euthanized, hearts removed, and suitable trabeculae harvested from the free wall of the right ventricle. Twitch contractions, calibrated bis-fura-2 calcium transients, and myofilament calcium sensitivity (potassium contractures) were measured at frequencies of 1, 2, 3, and 4 Hz. The force frequency response, relaxation frequency response, and calcium frequency relationships were significantly blunted, and diastolic tension significantly increased with frequency in the pulmonary artery banding rabbits compared with sham-operated animals. Myofilament calcium sensitivity was virtually identical at 1 Hz in the treatment versus sham group (pCa 6.11�0.03 versus 6.11�0.06), but the frequency-dependent desensitization that takes place in the sham group (ΔpCa 0.14�0.06, P <0.05) was not observed in the pulmonary artery banding animals (ΔpCa 0.02�0.05). Analysis of myofilament protein phosphorylation revealed that the normally observed frequency-dependent phosphorylation of troponin-I is lost in pulmonary artery banding rabbits. Conclusions— The frequency-dependent myofilament desensitization is significantly impaired in right ventricular hypertrophy and contributes to the frequency-dependent elevation of diastolic tension in hypertrophy.
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Ten weeks of pulmonary artery banding is sufficient to induce right ventricular hypertrophy in rabbits without signs and symptoms of heart failure, and with altered right atrial calcium handling.
“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).”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Varian, et al., 2009
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- Authors
- Varian, K. D., Kijtawornrat, A., Gupta, S. C., Torres, C. A. A., Monasky, M. M., Hiranandani, N., Delfin, D. A., Rafael-Fortney, J. A., Periasamy, M., Hamlin, R. L., & Janssen, P. M. L.
- Affiliations
- The Ohio State University (US)
- From the Department of Physiology and Cell Biology (K.D.V., S.C.G., C.A.A.T., M.M.M., N.H., M.P., P.M.L.J.), College of Medicine; Department of Veterinary Biosciences (A.K., R.L.H.), Ohio State University; QTest Labs, Inc (A.K., R.L.H.); and Department of Molecular and Cellular Biochemistry (D.A.D., J.A.R.-F.), College of Medicine, Ohio State University, Columbus, Ohio.
- Corresponding author
- Janssen, Paul M.L.
- Venue
- Circulation: Heart Failure
- Published
- 2009-09
- Volume
- 2
- Issue
- 5
- Pages
- 472-481
- ISSN
- 1941-3289 (ISSN-L)
- 1941-3297
- PMC
- PMC2768816
- OpenAlex
- W2140257824
- Cited by
- 39
- References
- 32
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 1 · 2012: 7
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Heart Failure (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons - East Tennessee State University (East Tennessee State University) (submittedVersion)
- Funders
- Ohio State University
- U.S. Public Health Service (K02-83957, R01 746387)
- National Heart, Lung, and Blood Institute (K02HL083957, R01HL073816)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- diastolic dysfunction, right ventricular hypertrophy, pulmonary artery banding, pressure overload, troponin I phosphorylation, calcium transients, diastolic tension, rabbit model
- MeSH terms
- Myosin Binding Protein C, Phospholamban, Actins, Animals, Calcium-Binding Proteins, Cardiac Pacing, Artificial, Carrier Proteins, Diastole, Disease Models, Animal, Male, Actin Cytoskeleton, Myocardial Contraction, Atrial Natriuretic Factor, Phosphorylation, Rabbits, Hypertrophy, Right Ventricular, Ventricular Dysfunction, Right, Myosin Light Chains, Troponin I, Sodium-Calcium Exchanger, Calcium Signaling, Troponin T, Cardiac Myosins, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Muscle Strength
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