Abstract 3499: Mechanisms of Protection Against Ischemia-Induced Transmural Reentry by Nicorandil
Introduction: The impact of nicorandil in an angina (IONA) study has demonstrated that nicorandil, a hybrid of nitrate and adenosine triphosphate (ATP)- sensitive potassium (K-ATP) channel opener, improves the prognosis of stable angina pectoris; however, whether nicorandil can prevent ventricular tachyarrhythmia (VT) during acute myocardial ischemia is still controversial.
Method and results: We examined the effect of nicorandil on electrophysiological parameters in the transmural wall and on transmural reentry induced during acute myocardial ischemia using optical mapping techniques. Optical action potentials were recorded from the entire transmural wall of arterially perfused canine left ventricular wedges during arterial occlusion for 20 min in the absence and presence of nicorandil and in the presence of HMR1098, a sarcolemmal K-ATP channel selective blocker, plus nicorandil. During endocardial pacing, nicorandil dose-dependently shortened transmural mean action potential duration (APD) before ischemia and further shortened it during ischemia compared to the control. In contrast, nicorandil did not change the dispersion of APD both before and during ischemia. HMR1098 inhibited transmural APD shortening by nicorandil before and during ischemia. Arterial occlusion decreased transmural conduction velocity (CV) regardless of intervention. Compared with the control, however, nicorandil alone and HMR1098 plus nicorandil increased transmural CV during 15–19 min of ischemia. Nicorandil significantly increased the extent of the non-excited area in the epicardium after 13 min of ischemia compared to the control and HMR1098 plus nicorandil. Isochrone maps during the initiation of VT showed that 1) epicardial muscle inactivation protected against the induction of transmural reentry and 2) slow impulse propagation induced a small reentrant circuit of transmural reentry.
Conclusions: Nicorandil augments epicardial muscle inactivation through the activation of sarcolemmal K-ATP channels and protects against transmural conduction slowing through mechanisms independent of sarcolemmal K-ATP channel activation, which may contribute to prevent VT induction during acute global ischemia.