Direct Protective Effects of Dexmedetomidine Against Myocardial Ischemia-Reperfusion Injury in Anesthetized Pigs

Systemic administration of α2-adrenergic agonists has been shown to protect ischemic myocardium, but the direct effects on ischemia-reperfused myocardium have not yet been clarified. This study was carried out to determine the effects of intracoronary dexmedetomidine (DEX) on the myocardial ischemia-reperfusion injury in anesthetized pigs. In open-chest pigs, the left anterior descending coronary artery was perfused through an extracorporeal circuit from the carotid artery. They received intracoronary infusion of DEX at a rate of 1 ng · mL−1 (group LD, n = 9), 10 ng · mL−1 (group MD, n = 9), or 100 ng · mL−1 (group HD, n = 9) of coronary blood flow or vehicle (group C, n = 12) for 30 min before ischemia. Myocardial stunning was produced by 12-min ischemia of the perfused area of left anterior descending coronary artery and 90-min reperfusion. The effect on reperfusion-induced arrhythmias was evaluated using the incidence of ventricular tachycardia or fibrillation after reperfusion. Regional myocardial contractility was evaluated with segment shortening (%SS). Dexmedetomidine significantly reduced the incidence of reperfusion-induced ventricular arrhythmias. Dexmedetomidine significantly improved the recovery of percentage segment shortening at 90 min after reperfusion (32.6% ± 3.1% in group C, 58.2% ± 2.1% in group LD, 61.1% ± 1.8% in group MD, and 72.0% ± 2.0% in group HD). Dexmedetomidine suppressed the increase in plasma norepinephrine concentration after reperfusion. The results indicate that DEX would exert the protective effect against ischemia-reperfusion injury by the direct action on the myocardium, which is not mediated through the central nervous system. ABBREVIATIONS VT—ventricular tachycardia VF—ventricular fibrillation NE—norepinephrine DEX—dexmedetomidine PaCO2—arterial carbon dioxide tension PaO2—arterial oxygen tension LAD—left anterior descending coronary artery CBF—coronary blood flow LV—left ventricular LVP—left ventricular pressure LVdP/dtmax—peak rate of increase in left ventricular pressure %SS—percentage of segment shortening RMBF—regional myocardial blood flow endo/epi—subendocardial to subepicardial