Simultaneous Measurement of the Mechanics and Energetics of Cardiac Trabeculae

Abstract

This study is the first to have measured, simultaneously, the mechanics and energetics of isolated mammalian cardiac trabeculae. Measurements were made using our unique micromechanocalorimeter and work-loop calorimeter. Using these two unique devices, we measured simultaneously the stress (force per cross-sectional area) production, muscle length change and heat output of isolated ventricular trabeculae from the rat heart. Trabeculae were superfused with 100%-oxygenated solution at room temperature (22°C - 24°C), and were predicted to have been supplied adequately with oxygen by diffusion. Under fixed-end contractions, the heat production of trabeculae is a linear, frequency-independent, but [Ca2+]o-dependent, function of their peak active stress and of their stress-length area (SLA: the area demarcated by the stress-length relations). The former relation revealed that increased diastolic stress, observed at relatively high stimulus frequency (4 Hz), is attained with negligible heat output - presumably due to attached, force-bearing, but non-ATP-hydrolysing, crossbridges. The latter relation is associated with prolongation of twitch duration as a direct consequence of cooperative binding of crossbridges. During work-loop contractions, in which trabeculae were required to perform external mechanical work, designed to mimic the pressure-volume work of the heart, right-ventricular (RV) trabeculae were found to have a greater maximum mechanical efficiency (ratio of work to change of enthalpy, -ΔH) than left-ventricular (LV) trabeculae (13% - 14% versus 10%). Consistent with the linear relation between oxygen consumption (VO2) and pressure-volume area (PVA) of the intact heart, first observed by Suga and colleagues, -ΔH (work plus heat) production of both RV and LV trabeculae is a linear function of SLA. The reciprocal of the slope of this relation (a measure of 'contractile efficiency' as proposed by Suga; we call it Suga's PVA-efficiency) is independent of ventricle-of-origin, but its intercept (an index of metabolic cost of activation due to Ca2+ cycling) is lower in RV trabeculae, leading them to have comparably greater maximum mechanical efficiency. Correction for the metabolic cost of activation rendered the maximum crossbridge efficiency equal in the two ventricles. Under both fixed-end and work-loop contractions, the 'potential energy' component of SLA is not only proportional to the time-integral of twitch stress production, but is also a linear function of heat production. Both components of SLA ('potential energy' and work) are proportional to distinct segments under the stress-time profiles. This finding provides insight into the much-observed, but ill-understood, linear VO2-PVA relation of the heart.