Abstract 11924: Nicorandil Attenuates Ventricular Dysfunction in a Piglet Model of Cardiopulmonary Bypass and Cardioplegic Arrest

Abstract

Introduction: Nicorandil is a coronary vasodilator for treatment of ischemia-induced angina. Studies suggest nicorandil may offer myocardial protection against regional ischemia-reperfusion (IR) injury during coronary artery bypass grafting in adults. The impact of nicorandil on global IR-induced myocardial injury and left ventricular (LV) dysfunction after cardiopulmonary bypass (CPB) and cardioplegic arrest (CA) has not been investigated in children. Hypothesis: Nicorandil attenuates myocardial IR injury and LV dysfunction after CPB and CA in an immature animal model. Methods: Anesthetized piglets (4-5 weeks-old, 8.8±0.4 kg) were cannulated via the right atrium and ascending aorta for initiation of full-flow CPB (100 mL/kg/min). Following 30 mins of aortic cross-clamp (ACC) and CA, hearts were reperfused on full CPB for 60 mins, followed by partial CPB for 30 mins, and separation from CPB for 30 mins. Nicorandil (0.2 mg/kg IV bolus + 0.02 mg/kg/min IV continuous infusion) or saline (N=6 per group) was initiated 5 mins before ACC and continued throughout the protocol. Temperature, ECG, mean arterial pressure (MAP), and LV function (via high-fidelity Millar pressure catheter) were continuously recorded. Serial plasma samples were collected for measurement of oxidant stress, inflammation, and multi-organ injury (heart, lung, kidney, and brain). Results: Temperature, heart rate, and MAP were similar between nicorandil- and saline-treated groups. However, 120 mins after ACC removal, nicorandil treatment significantly improved LV contractility [LV +dP/dt: 2,962±678 mmHg/sec (nicorandil) vs. 1,278±332 mmHg/sec (saline), p=0.004] and LV relaxation [LV -dP/dt: -2,670±454 mmHg/sec (nicorandil) vs. -1,347±339 mmHg/s (saline), p=0.002]. Also, nicorandil significantly attenuated the IR-induced increase in circulating biomarkers for oxidant stress, inflammation, and multi-organ injury. Conclusions: In a piglet model of CPB with CA, nicorandil attenuates LV systolic and diastolic dysfunction and improves oxidant stress, inflammation, and multi-organ injury. These results suggest that nicorandil may prove beneficial to mitigate IR injury and accelerate LV functional recovery after open heart surgery in infants and children.