Arrhythmia and electrical heterogeneity during prolonged hypoxia in guinea pig papillary muscles

To investigate the mechanism of late arrhythmias in myocardial ischemia, effects of prolonged substrate-free hypoxia or hypoxia with glycolytic inhibition on action potentials of guinea pig papillary muscles were studied. During substrate-free hypoxia, the action potential duration (APD) shortened until 120-210 min, and there was recovery of the APDs thereafter. Surface mapping after prolonged hypoxia showed various APDs in single muscles. Hypoxia with glycolytic inhibition (20 mM 2-deoxyglucose) caused the recovery of APDs after 90 min. The double-microelectrode method confirmed different APDs and action potential configurations (electrical heterogeneity) in these conditions. There were triggered activities as a result of delayed afterdepolarizations, an indication of Ca2+ overload after prolonged hypoxia. There was also conduction delay between two recording sites. It was shown, for the first time, that triggered activities, recovery of APDs, electrical heterogeneity, and conduction delay appear after prolonged hypoxia. It is suggested that electrical heterogeneity and conduction delay caused by cell-to-cell uncoupling may predispose cardiac tissue to reentrant arrhythmias during ischemia.