Experimental and modelling evidence of shortening heat in cardiac muscle

• Published in: The Journal of physiology 2017-10, Vol.595 (19), p.6313-6326
• Main Authors: Tran, Kenneth, Han, June‐Chiew, Crampin, Edmund John, Taberner, Andrew James, Loiselle, Denis Scott
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Animals; cardiac energetics; Cardiac muscle; Computer applications; Computer simulation; cross‐bridge model; Cycles; Cytoskeleton - metabolism; Energy expenditure; Energy Metabolism; Experiments; Heart diseases; Heat; Hot Temperature; Kinetics; Male; Models, Cardiovascular; Muscle; Muscle contraction; Musculoskeletal system; Myocardial Contraction; Partitioning; partitioning heat; Rats; Rats, Sprague-Dawley; Research Paper; Skeletal muscle; Thermodynamics; Uncertainty
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/JP274680

Key points Heat associated with muscle shortening has been repeatedly demonstrated in skeletal muscle, but its existence in cardiac muscle remains contentious after five decades of study. By iterating between experiments and computational modelling, we show compelling evidence for the existence of shortening heat in cardiac muscle and reveal, mechanistically, the source of this excess heat. Our results clarify a long‐standing uncertainty in the field of cardiac muscle energetics. We provide a revised partitioning of cardiac muscle energy expenditure to include this newly revealed thermal component. When a muscle shortens against an afterload, the heat that it liberates is greater than that produced by the same muscle contracting isometrically at the same level of force. This excess heat is defined as ‘shortening heat’, and has been repeatedly demonstrated in skeletal muscle but not in cardiac muscle. Given the micro‐structural similarities between these two muscle types, and since we imagine that shortening heat is the thermal accompaniment of cross‐bridge cycling, we have re‐examined this issue. Using our flow‐through microcalorimeter, we measured force and heat generated by isolated rat trabeculae undergoing isometric contractions at different muscle lengths and work‐loop (shortening) contractions at different afterloads. We simulated these experimental protocols using a thermodynamically constrained model of cross‐bridge cycling and probed the mechanisms underpinning shortening heat. Predictions generated by the model were subsequently validated by a further set of experiments. Both our experimental and modelling results show convincing evidence for the existence of shortening heat in cardiac muscle. Its magnitude is inversely related to the afterload or, equivalently, directly related to the extent of shortening. Computational simulations reveal that the heat of shortening arises from the cycling of cross‐bridges, and that the rate of ATP hydrolysis is more sensitive to change of muscle length than to change of afterload. Our results clarify a long‐standing uncertainty in the field of cardiac muscle energetics. Key points Heat associated with muscle shortening has been repeatedly demonstrated in skeletal muscle, but its existence in cardiac muscle remains contentious after five decades of study. By iterating between experiments and computational modelling, we show compelling evidence for the existence of shortening heat in cardiac muscle and reveal, me