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

Am J Physiol Heart Circ Physiol. 2002 Apr;282(4):H1311-9. doi: 10.1152/ajpheart.00464.2001.

Abstract

We examined the contributions of the Ca(2+) channels of the sarcolemma and of the sarcoplasmic reticulum to electromechanical restitution. Extrasystoles (F(1)) were interpolated 40-600 ms following a steady-state beat (F(0)) in perfused rat ventricles paced at 2 or 3 Hz. Plots of F(1)/F(0) 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 microM thapsigargin plus 200 nM ryanodine and unaffected by KN-93 and KB-R7943. Phase II was accelerated by the Ca(2+) 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 Ca(2+) current facilitation, whereas phase II represents the recovery of the ability of the sarcoplasmic reticulum to release Ca(2+).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Action Potentials / physiology
  • Animals
  • Benzylamines / pharmacology
  • Calcium Channel Agonists / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / physiology*
  • Enzyme Inhibitors / pharmacology
  • Heart / drug effects
  • Heart / physiology*
  • Heart Rate
  • In Vitro Techniques
  • Isoproterenol / pharmacology
  • Male
  • Perfusion
  • Pyrroles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Ryanodine / pharmacology
  • Sarcolemma / physiology
  • Sarcoplasmic Reticulum / physiology*
  • Sulfonamides / pharmacology
  • Systole
  • Thapsigargin / pharmacology
  • Time Factors
  • Vasodilation
  • Ventricular Function, Left / physiology*

Substances

  • Benzylamines
  • Calcium Channel Agonists
  • Calcium Channel Blockers
  • Calcium Channels
  • Enzyme Inhibitors
  • Pyrroles
  • Sulfonamides
  • FPL 64176
  • KN 93
  • Ryanodine
  • Thapsigargin
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Isoproterenol