Creatine phosphate and protection against reperfusion-induced arrhythmias in the rat heart

Abstract

An isolated perfused working rat heart preparation was used to assess the effect of including creatine phosphate (10 mmol/1) in the perfusion fluid of hearts subjected to aerobic perfusion (20 min), regional ischaemia (15 min) and reperfusion (2 min). Creatine phosphate had no detectable effect upon pre-ischaemic, ischaemic or post-ischaemic contractile function, it also had no statistically significant effect upon myocardial tissue ATP content. However, creatine phosphate was found to afford striking protection against reperfusion-induced arrhythmias. The incidence of ventricular fibrillation was reduced from over 80% ( 13 16 ) in the control group to 10% in the creatine phosphate-treated group (P less than 0.001). Possible mechanis,s underlying the anti-arrhythmic effects of creatine phosphate were investigated using isolated rat papillary muscles superfused with or without added creatine phosphate (10 mmol/1). During aerobic superfusion at 37°C creatine phosphate did not cause any statistically significant changes in contractile (developed tension) or electrophysiological ( dV dt max and action potential duration) indices. Creatine phosphate did however influence the extent to which hypoxia (10 min) and reoxygenation (10 min) altered tension and electrophysiological characteristics. It accelerated the hypoxia-induced decline in developed tension and also the reoxygenation-induced recovery of developed tension. Relatively small changes in dV dt max and action potential duration were observed during hypoxia and these rapidly normalized during reoxygenation. In general creatine phosphate acted to exacerbate any changes during hypoxia and accelerate the recovery during reoxygenation. While some of the electrophysiological changes observed would indicate an anti-arrhythmic effect, they were relatively small and perhaps insufficient to explain fully the potent anti-arrhythmic properties of creatine phosphate.