Cardioprotective effect of nicorandil against myocardial injury following cardiac arrest in swine
Nicorandil, a vasodilatory drug used to treat angina, was reported to protect against myocardial ischemia-reperfusion injury in various animal models. However, its cardioprotective action following cardiac arrest is unknown. We examined the cardioprotective effects of nicorandil in a porcine model of cardiac arrest and resuscitation.Methods
Ventricular fibrillation was induced electrically for 4 min in anesthetized domestic swine, followed by cardiopulmonary resuscitation. Sixteen successfully resuscitated animals were randomized to saline control (n = 8) or nicorandil (n = 8) groups. Nicorandil (150 μg/kg) was administered by central intravenous injection at onset of restoration of spontaneous circulation (ROSC), followed by 3 μg/kg/min infusion until reperfusion end. Sham-operated animals received surgery only (n = 4). Hemodynamic parameters were monitored continuously. Blood samples were taken at baseline, 5, 30, 180, and 360 min after ROSC. Left ventricular ejection fraction was assessed by echocardiography at baseline and 6 h after ROSC. The animals were euthanized 6 h after ROSC, and the cardiac tissue was removed for analysis.Results
6 h after ROSC, nicorandil had significantly improved all hemodynamic variables (all P < 0.05) except the maximum rate of left ventricular pressure decline and heart rate (P > 0.05) compared with the control group. Control animals showed elevated cardiac troponin I and lactate levels compared with sham animals, which were significantly decreased following nicorandil treatment (P < 0.05). In the saline control group, the adenosine triphosphate (ATP) content was largely reduced but subsequently rescued by nicorandil (P < 0.05). Histopathologic injury was reduced with nicorandil treatment. Nicorandil reduced cardiomyocyte apoptosis as evidenced by reduced terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells, decreased Bax and caspase-3 expression, and increased Bcl-2 expression in the myocardium (all P < 0.05).Conclusion
Nicorandil exhibited cardioprotective effects on myocardial injury following cardiac arrest via improvement in post-resuscitation myocardial dysfunction and energy metabolism, reduction in myocardial histopathologic injury, and antiapoptotic effects.