Cellular electrophysiological effects of hyperthermia on isolated guinea pig papillary muscle. Implications for catheter ablation.

BACKGROUND: The primary mechanism of tissue injury by radiofrequency catheter ablation is presumed to be thermally mediated. However, the myocardial cellular electrophysiological effects of hyperthermia are not well characterized. We used an in vitro model of isolated guinea pig right ventricular papillary muscle to investigate the acute cellular electrophysiological effects of hyperthermia. METHODS AND RESULTS: Excised guinea pig right ventricular papillary muscles were pinned in a high-flow tissue bath and superfused with Tyrode's solution at 37.0 +/- 0.5 degrees C. The superfusate temperature was rapidly changed to 38.0 to 56.0 degrees C for 60 seconds and then returned to 37.0 degrees C. Conventional microelectrodes were used to measure membrane potential (Vm), maximum rate of rise of the action potential (dV/dtmax), and action potential (AP) amplitude and AP duration at 50% (APD50) and 90% (APD90) repolarization. Hyperthermia resulted in (1) a progressive depolarization of Vm at temperatures > or = 40.0 degrees C, which became more prominent at temperatures > or = 45.0 degrees C; (2) changes in the AP characterized by a temperature-dependent increase in dV/dtmax and a temperature-dependent decrease in AP amplitude, APD50, and APD90; (3) reversible loss of cellular excitability within a temperature range of 42.7 to 51.3 degrees C (median, 48.0 degrees C); (4) irreversible loss of cellular excitability and tissue injury at temperatures > or = 50.0 degrees C; and (5) the development of abnormal automaticity at temperatures > 45.0 degrees C. CONCLUSIONS: Hyperthermia causes significant changes in myocardial cellular electrophysiological properties that include membrane depolarization, reversible and irreversible loss of excitability, and abnormal automaticity. There appear to be specific temperature ranges for reversible and irreversible electrophysiological changes. These observations may have important implications for tissue temperature monitoring during radiofrequency catheter ablation.