Myocardial twitch duration and the dependence of oxygen consumption on pressure-volume area: experiments and modelling.
ABSTRACT Key points The energy expenditure of the heart is linearly related to its work performance, as measured by its development of pressure-volume area. We have explored the basis of this phenomenon both experimentally (by measuring the heat production of isolated ventricular tissue undergoing cyclic contraction and relaxation) and theoretically (using mathematical modelling). We provide the first evidence that the heat production of isolated trabeculae undergoing fixed-end contractions varies linearly with force-length area, and confirm that twitch duration increases progressively with muscle length. Mathematical modelling reveals that length-dependent prolongation of the twitch reflects length- (or, equivalently, force-) dependent binding of Ca(2+) to troponin-C, together with Ca(2+)-dependent crossbridge cooperativity. Mathematical modelling further reveals that the apparent linear dependence of heat production on force-length area is remarkably robust against departures from the linearity of length-dependent twitch duration.
Article: Combining Wet and Dry Research: Experience with Model Development for Cardiac Mechano-Electric Structure-Function Studies.[show abstract] [hide abstract]
ABSTRACT: Since the development of the first mathematical cardiac cell model 50 years ago, computational modelling has become an increasingly powerful tool for the analysis of data and for integration of information related to complex cardiac behaviour. Current models build on decades of iteration between experiment and theory, representing a collective understanding of cardiac function. All models, whether computational, experimental, or conceptual, are simplified representations of reality and, like tools in a toolbox, suitable for specific applications. Their range of applicability can be explored (and expanded) by iterative combination of 'wet' and 'dry' investigation, where experimental or clinical data are used to first build and then validate computational models (allowing integration of previous findings, quantitative assessment of conceptual models, and projection across relevant spatial and temporal scales), while computational simulations are utilised for plausibility assessment, hypotheses-generation, and prediction (thereby defining further experimental research targets). When implemented effectively, this combined wet/dry research approach can support the development of a more complete and cohesive understanding of integrated biological function. This review illustrates the utility of such an approach, based on recent examples of multi-scale studies of cardiac structure and mechano-electric function.Cardiovascular research 01/2013; · 5.80 Impact Factor