END-SYSTOLIC PRESSURE-VOLUME RELATIONSHIP AND INTRACELLULAR CONTROL OF CONTRACTION

The left ventricular (LV) pressure-volume relationship and the effect of ejection on pressure generation are predicted theoretically based o n 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 sugg ests two feedback control loops: 1) a positive cooperative mechanism t hat determines the force-length relationship, the length dependence ca lcium sensitivity of the contractile filaments, and the related Frank Starling law; and 2) a negative mechanical feedback. that determines t he force-velocity relationship and the generated power. The interplay between these two feedback mechanisms explains the wide spectrum of ph enomena 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 o n the ESPVR, i.e,, the increase of the end-systolic pressure of the ej ecting beat over the pressure of the isovolumic beat at the same end-s ystolic volume. Furthermore, the analysis suggests that the LV contrac tility depends on the balance between the two intracellular mechanisms and that the effect of loading conditions is determined through these intracellular mechanisms.