Department of Anesthesiology, Nagasaki University School of Medicine, Nagasaki, Japan.
Shock. 2012 Jul;38(1):92-7. doi: 10.1097/SHK.0b013e318254d3fb.
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.
全身给予α2-肾上腺素能激动剂已被证明可保护缺血心肌，但对缺血再灌注心肌的直接作用尚未阐明。本研究旨在确定冠状动脉内给予右美托咪定（DEX）对麻醉猪心肌缺血再灌注损伤的影响。在开胸猪中，通过颈动脉体外循环对左前降支冠状动脉进行灌注。在缺血前 30 分钟，它们接受 1ng·mL-1（LD 组，n=9）、10ng·mL-1（MD 组，n=9）或 100ng·mL-1（HD 组，n=9）的冠状动脉内输注或载体（C 组，n=12）。缺血灌注区左前降支冠状动脉缺血 12 分钟，再灌注 90 分钟。通过再灌注后室性心动过速或纤颤的发生率评估再灌注诱导性心律失常的影响。用节段缩短率（%SS）评估局部心肌收缩力。右美托咪定显著降低了再灌注诱导性室性心律失常的发生率。右美托咪定显著改善了再灌注后 90 分钟的节段缩短率恢复（C 组 32.6%±3.1%，LD 组 58.2%±2.1%，MD 组 61.1%±1.8%，HD 组 72.0%±2.0%）。右美托咪定抑制了再灌注后血浆去甲肾上腺素浓度的升高。结果表明，DEX 通过对心肌的直接作用发挥其对缺血再灌注损伤的保护作用，而不是通过中枢神经系统介导的。
