End-systolic pressure-volume relationship and intracellular control of contraction.

Abstract

The left ventricular (LV) pressure-volume relationship and the effect of ejection on pressure generation are predicted theoretically based on the intracellular control mechanisms. The control of contraction is described based on coupling calcium kinetics and cross-bridge cycling. The analysis of published skinned and intact cardiac muscle data suggests two feedback control loops: 1) a positive cooperative mechanism that determines the force-length relationship, the length dependence calcium sensitivity of the contractile filaments, and the related Frank Starling law; and 2) a negative mechanical feedback that determines the force-velocity relationship and the generated power. The interplay between these two feedback mechanisms explains the wide spectrum of phenomena associated with the end-systolic pressure-volume relationship (ESPVR); it provides an explanation for the "shortening deactivation" and for the recent observations of the positive effect of ejection on the ESPVR, i.e., the increase of the end-systolic pressure of the ejecting beat over the pressure of the isovolumic beat at the same end-systolic volume. Furthermore, the analysis suggests that the LV contractility depends on the balance between the two intracellular mechanisms and that the effect of loading conditions is determined through these intracellular mechanisms.