Phase I and phase II of short-term mechanical restitution in perfused rat left ventricles

Abstract

We examined the contributions of the Ca2+ channels of the sarcolemma and of the sarcoplasmic reticulum to electromechanical restitution. Extrasystoles (F1) were interpolated 40–600 ms following a steady-state beat (F0) in perfused rat ventricles paced at 2 or 3 Hz. Plots of F1/F0 versus the extrasystolic interval consisted of phase I, which occurred before relaxation of the steady-state beat, and phase II, which occurred later. Phase I exhibited a period of enhanced left ventricular pressure development that coincided with action potential prolongation. Phase I was eliminated by −BAY K 8644 (100 nM) and FPL 64176 (150 nM), augmented by 3 μM thapsigargin plus 200 nM ryanodine and unaffected by KN-93 and KB-R7943. Phase II was accelerated by the Ca2+channel agonists and by isoproterenol but was eliminated by thapsigargin plus ryanodine. The results suggest that phase I of electromechanical restitution is caused by a transient L-type Ca2+ current facilitation, whereas phase II represents the recovery of the ability of the sarcoplasmic reticulum to release Ca2+.