Heptanol decreases the incidence of ischemia-induced ventricular arrhythmias through altering electrophysiological properties and connexin 43 in rat hearts.

Abstract

Heptanol is a type of gap junction inhibitor that decreases electrical conduction velocity. However, little is known regarding the effects of heptanol on the arrhythmias induced by regional myocardial ischemia. This study aimed to investigate the effects of heptanol on ventricular arrhythmias and the underlying mechanisms. On the Langendorff apparatus, isolated hearts of Sprague-Dawley rats underwent 30 min of ischemia, with or without pretreatment with heptanol (0.1, 0.3 or 0.5 mM), 15 min prior to the induction of regional ischemia through ligation of the left anterior descending coronary artery. The incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) were recorded after ligation. Heptanol decreased the incidence of ventricular arrhythmias (45% in the control group vs. 10% in the 0.1 mM group, 0% in the 0.3 mM group and 0% in the 0.5 mM group, P<0.05), whereas it prolonged the PR interval, QT interval and monophasic action potential duration at 90% repolarization (MAPD90). As evaluated with immunofluorescence microscopy, heptanol was able to partly reverse the downregulation of connexin 43 (Cx43) induced by ischemia. The results of the reverse transcription-polymerase chain reaction were consistent with those of immunofluorescence. In conclusion, heptanol significantly decreased the incidence of VT and VF induced by regional ischemia and prolonged the PR interval, QT interval and MAPD90. Heptanol also partly reversed the downregulation of Cx43 induced by ischemia.