Rebuttal from Shmuylovich, Chung, and Kovacs

In key contrast to our view (6), Yellin and Nikolic suggest that “LV volume clamping … allows the ventricle to completely relax without relengthening” (8). However, recent studies show strong coupling between cross-bridge deactivation/relaxation and elastic recoil/relengthening. Deactivation independently accounts for only 3–5% of maximal force (i.e., pressure) decline after calcium activation, while the majority of force (pressure) decline occurs with sarcomere relengthening (7). This is in precise agreement with chamber mechanics, where, during and after calcium sequestration (3), elastic recoil (motion) is observed, manifesting as torsion during isovolumic relaxation (5). This conceptual foundation motivated our model that accurately predicts isovolumic pressure decline by unifying recoil and deactivation (2).

Indeed, the dynamic balance between stored elastic energy and cross-bridge deactivation determines wall stress and resulting decreasing chamber pressure (2, 3, 7). Deactivation alone cannot drop pressures fully. Only motion, i.e., the expansion of the ventricle faster than it can fill, can generate the atrioventricular pressure gradient to initiate suction. Chamber expansion would not occur if relaxation (cross-bridge uncoupling) were not coupled with release of stored elastic energy, i.e., recoil.

Yellin and Nikolic's assertion that diastasis “has no relation to elastic recoil, since … 80% of filling has occurred” (8) ignores the kinematics. The fact that diastasis follows recoil assures causality. Atrial contraction and ventricular systole displace the ventricle from equilibrium and only during diastasis are forces, flows, and strains reequilibrated (6). This is consistent with the fact that all hearts are suction pumps, but does not imply that failing hearts cannot be suction pumps; in fact, studies that quantify suction demonstrate the opposite (4, 9).

Yellin and Nikolic note the intrinsic variability of diastasis (8). At low heart rates diastasis is unambiguous, but diastasis can vary from beat-to-beat and may be masked by atrial contraction (1). Variation in diastatic pressure and volume is due to load, atrial properties, and ventricular properties, but that does not negate the functional role of diastasis as the equilibrium volume. Ventricular and atrial tone, contractility, and load balance at diastasis are dynamic physiological variables. Thus equilibrium volume must also be dynamic. In fact, quantifying diastatic pressure and volume variation provides fundamental chamber properties in the form of passive stiffness (10).

Hence, concluding that equilibrium volume must be the volume at diastasis is just one of several insights gained by a kinematic perspective of diastole. It consolidates a range of observations by providing consistency with and between experiments, from the myofiber to the ventricle, and from ventricular development to disease (2, 4, 6, 7, 9, 10).