Post‐Rest Potentiation and its Decay after Inotropic Interventions in Isolated Rat Heart Muscle

Abstract

The effects of various inotropic interventions on post-rest potentiation and its decay were investigated in isolated cardiac muscle. The inotropic interventions studied were: reduced extracellular Na+ and elevated extracellular Ca2+ concentration; exposure to ouabain, monensin, isoprenaline, phenylephrine and cirazoline. Force of contraction (stimulation frequency 2 Hz) was measured isometrically in left atria and right ventricular strips of rat hearts. Maximum post-rest potentiation was reached after 10 sec. of rest and amounted to 245 +/- 26% of pre-rest control in ventricle and 192 +/- 15% in atria. Ca(2+)-recirculation fraction was calculated from the decay of post-rest potentiation after resumption of regular stimulation, it was 0.77 +/- 0.01 in 11 control ventricular strips. High concentrations of caffeine (3 mmol/l) completely abolished post-rest potentiation in both tissues. The development of post-rest potentiation was accelerated in the presence of most of the inotropic agents. However, with the exception of ouabain and only in atrial muscle, none of the inotropic interventions produced higher post-rest contraction amplitudes than during controls. In rat heart muscle, the inotropic interventions studied are not any more effective in augmenting force of contraction than prolonged stimulation intervals. This suggests that (1) the distribution of Ca2+ into the sarcoplasmic reticulum is at a maximum during post-rest potentiation; (2) modifications of signal transduction pathways cannot further increase post-rest potentiation; and therefore that (3) shifts in Ca2+ distribution act as a limiting factor.

Remodelamento miocárdico após grandes infartos converte potenciação pós-pausa em decaimento da força em ratos

“…Normally, as most of the Ca 2+ returns to the SR during the rest period, its content tends to increase with increased duration of the pause, also increasing Ca 2+ release and, finally, the force generation upon the next activation 1 . In fact, the administration of Ry to block SR function in our experiments completely abolished the PRC potentiation of C muscles, reinforcing previous reports describing the key role of SR storing function in this phenomenon 4 . On the other hand, the inhibition of transsarcolemmal Ca 2+ extrusion by NCX in our preparations (by using Li + ) enhanced the potentiation of C muscles, which confirms the importance of Ca 2+ efflux mechanisms to negatively modulate the PRC of rat LV muscle 6,7 .…”

“…Thus, changes in rate and rhythm are frequently used as experimental maneuvers to evaluate the behavior or disclose abnormalities of Ca 2+ kinetics on the excitation-contraction coupling 3 . Accordingly, post-rest contraction (PRC) allows indirect evaluation of the SR function 2,4,5 . In the myocardium of normal rats, PRC is potentiated due to the additional Ca 2+ accumulated in the SR during the pause due to SR Ca 2+ -ATPase (SERCA2) activity and the increased fractional Ca 2+ release 2,5 upon activation.…”

Mechanical Restitution in Atrial Muscle from Human and Rat Hearts: Effects of Agents that Modify Sarcoplasmic Reticulum Function

“…1 A. In all human preparations, shorter than regular intervals produced smaller contraction amplitudes (extrasystoles) followed by Ravens et al 1995). With 4 human atrial muscles, decay of post-rest potentiation was similar as observed in rat muscles (not shown).…”

“…Caffeine (3 mM) did not significantly affect steadystate force of contraction, but clearly abolished the post-rest potentiation phase in rat (Ravens et al 1995) and human (this paper) atrial muscle. Complete emptying of the sarcoplasmic reticulum Ca2+ stores by caffeine requires high concentrations (>lo mM) (Weber & Herz 1968;Thorpe 1973).…”

“…The aim of this study was to characterize the role of the sarcoplasmic reticulum in the three phases of mechanical restitution curve in human and rat atrial tissue by employing pharmacological tools. Caffeine was used for comparison with results from previous studies: in a concentration that does not affect steady-state contraction, caffeine abolishes the phase of post-rest po- tentiation in rat myocardium (Ravens et al 1995; and also interferes with Ca2+ uptake into the sarcoplasmic reticulum (Weber & Herz 1968;Fuchs 1969). We used the direct stimulator of the adenylyl cyclase, forskolin (Metzger & Lindner 1981) for loading the sarcoplasmic reticulum with Ca".…”