FUNCTIONAL AND ELECTROPHYSIOLOGICAL EFFECTS OF OXIDANT STRESS ON ISOLATED VENTRICULAR MUSCLE - A ROLE FOR OSCILLATORY CALCIUM RELEASE FROM SARCOPLASMIC-RETICULUM IN ARRHYTHMOGENESIS

Study objective - The aim was to investigate the cellular basis of oxidant stress induced arrhythmias by studying the influence of oxidant stress on the contractile and electrophysiological function of isolated cardiac muscle. Design - Oxidant stress was induced by the photoactivation of rose bengal added to the solution superfusing isolated ventricular muscles from a number of species. Measurements of contractile and electrophysiological function were made under control conditions, during exposure to oxidant stress, and under a number of experimental conditions. Experimental material - Isolated superfused papillary muscles or trabeculae from rat, rabbit, or frog hearts were used in all studies. Measurements and main results - The contractile response to oxidant stress was assessed by measuring isometric developed tension and resting tension throughout the experiment, and the electrophysiological response was assessed by recording action potentials using conventional 3 M KCl filled intracellular electrodes. Oxidant stress induced a transient positive inotropy, after-contractions, and eventually contracture. Associated with these contractile changes were prolongation of the action potential, early afterdepolarisations, oscillations in resting membrane potential, and automaticity. These effects were concentration and species dependent and the oscillations in both tension and membrane potential were abolished by inhibition of calcium release from the sarcoplasmic reticulum with caffeine. Conclusions - The contractile and electrophysiological effects of rose bengal induced oxidant stress are consistent with a cellular calcium overload. The observation that the oscillations in tension and membrane potential were abolished by caffeine and that these effects were species dependent (rat > rabbit > frog) suggests a role for oscillatory sarcoplasmic reticulum calcium release in these effects. The oscillations in membrane potential and the automaticity induced by rose bengal are likely to underlie the arrhythmias observed in isolated hearts exposed to oxidant stress that have previously been described.