Heat‐Stress Responses Modulate Beta‐Adrenergic Agonist and Angiotensin II Effects on the Arrhythmogenesis of Pulmonary Vein Cardiomyocytes

Effect of Heat Stress on Pulmonary Vein Cardiomyocytes. Introduction: Heat stress‐induced responses reduce the occurrence of atrial fibrillation (AF). Pulmonary vein (PV) cardiomyocytes with pacemaker activity play a critical role in the pathophysiology of AF. In this study, we examined whether heat‐stress responses alter the electrophysiological characteristics of PV cardiomyocytes and protect the PV against angiotensin II‐ or isoproterenol‐induced arrhythmogenesis. Methods and Results: We used whole‐cell patch clamp techniques to investigate the spontaneous activity and ionic currents in single isolated rabbit PV pacemaker cardiomyocytes with or without (control) exposure to heat stress (43°C, 15 minutes) 5 ± 1 hours before the experiments. Compared to control cardiomyocytes, heat‐stressed PV cardiomyocytes had slower beating rates. Heat‐stressed PV cardiomyocytes had larger L‐type calcium currents, transient outward currents, smaller inward rectifier potassium currents, but similar sodium‐calcium exchanger currents_. Additionally, heat‐stressed PV cardiomyocytes had a lower incidence of pacemaker currents than control PV cardiomyocytes. Moreover, isoproterenol increased the beating rate of control cardiomyocytes but not heat‐stressed PV cardiomyocytes. Similarly, angiotensin II also increased the beating rate of control cardiomyocytes, but not heat‐stressed PV cardiomyocytes, in association with decreased expression of the angiotensin II type 1 receptor. Conclusion: Heat‐stress responses altered the electrophysiological characteristics of PV cardiomyocytes and attenuated the effects of isoproterenol and angiotensin II on PV arrhythmogenesis, which may play a role in the protective potential of heat‐stress responses. (J Cardiovasc Electrophysiol, Vol. 22, pp. 183‐190, February 2011)