Increased heart size is a major risk factor for heart failure and premature mortality. Although abnormal heart growth subsequent to hypertension often accompanies disturbances in mechano-energetics and cardiac efficiency, it remains uncertain whether hypertrophy is their primary driver. In this study, we aimed to investigate the direct association between cardiac hypertrophy and cardiac mechano-energetics using isolated left-ventricular trabeculae from a rat model of primary cardiac hypertrophy and its control. We evaluated energy expenditure (heat output) and mechanical performance (force length work production) simultaneously at a range of preloads and afterloads in a microcalorimeter, we determined energy expenditure related to cross-bridge cycling and Ca2+ cycling (activation heat), and we quantified energy efficiency. Rats with cardiac hypertrophy exhibited increased cardiomyocyte length and width. Their trabeculae showed mechanical impairment, evidenced by lower force production, extent and kinetics of shortening, and work output. Lower force was associated with lower energy expenditure related to Ca2+ cycling and to cross-bridge cycling. However, despite these changes, both mechanical and cross-bridge energy efficiency were unchanged. Our results show that cardiac hypertrophy is associated with impaired contractile performance and with preservation of energy efficiency. These findings provide direction for future investigations targeting metabolic and Ca2+ disturbances underlying cardiac mechanical and energetic impairment in primary cardiac hypertrophy.
Cardiac mechanical efficiency is preserved in primary cardiac hypertrophy despite impaired mechanical function
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June-Chiew Han, Kenneth Tran, David J. Crossman, Claire L. Curl, Parisa Koutsifeli, Joshua P.H. Neale, Xun Li, Stephen B. Harrap, Andrew J. Taberner, Lea M.D. Delbridge, Denis S. Loiselle, Kimberley M. Mellor; Cardiac mechanical efficiency is preserved in primary cardiac hypertrophy despite impaired mechanical function. J Gen Physiol 2 August 2021; 153 (8): e202012841. doi: https://doi.org/10.1085/jgp.202012841
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