Shirakawa Makoto, Imura Hajime, Nitta Takashi
Department of Cardiovascular Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
Department of Cardiovascular Surgery, Nippon Medical School Musashikosugi Hospital, 1-396 Kosugicho, Nakahara-ku, Kawasaki, Kanagawa 211-8533, Japan.
Biomed Res Int. 2014;2014:601250. doi: 10.1155/2014/601250. Epub 2014 Aug 27.
The general anesthetic propofol protects the adult heart against ischemia and reperfusion injury; however, its efficacy has not been investigated in the immature heart. This work, for the first time, investigates the cardioprotective efficacy of propofol at clinically relevant concentrations in the immature heart. Langendorff perfused rabbit hearts (7-12 days old) were exposed to 30 minutes' global normothermic ischemia followed by 40 minutes' reperfusion. Left ventricular developed pressure (LVDP) and coronary flow were monitored throughout. Lactate release into coronary effluent was measured during reperfusion. Microscopic examinations of the myocardium were monitored at the end of reperfusion. Hearts were perfused with different propofol concentrations (1, 2, 4, and 10 μg/mL) or with cyclosporine A, prior to ischemic arrest and for 20 minutes during reperfusion. Propofol at 4 and 10 μg/mL caused a significant depression in LVDP prior to ischemia. Propofol at 2 μg/mL conferred significant and maximal protection with no protection at 10 μg/mL. This protection was associated with improved recovery in coronary flow, reduced lactate release, and preservation of cardiomyocyte ultrastructure. The efficacy of propofol at 2 μg/mL was similar to the effect of cyclosporine A. In conclusion, propofol at a clinically relevant concentration is cardioprotective in the immature heart.
全身麻醉药丙泊酚可保护成年心脏免受缺血再灌注损伤;然而,其在未成熟心脏中的疗效尚未得到研究。这项工作首次研究了丙泊酚在未成熟心脏中临床相关浓度下的心脏保护作用。采用Langendorff灌注兔心脏(7 - 12日龄),使其经历30分钟的全心常温缺血,随后再灌注40分钟。全程监测左心室舒张末压(LVDP)和冠状动脉血流量。在再灌注期间测量冠状动脉流出液中的乳酸释放量。在再灌注结束时对心肌进行显微镜检查。在缺血停搏前及再灌注期间20分钟,用不同浓度的丙泊酚(1、2、4和10μg/mL)或环孢素A灌注心脏。缺血前,4和10μg/mL的丙泊酚可显著降低LVDP。2μg/mL的丙泊酚具有显著且最大程度的保护作用,而10μg/mL则无保护作用。这种保护作用与冠状动脉血流量的恢复改善、乳酸释放减少以及心肌细胞超微结构的保存有关。2μg/mL丙泊酚的疗效与环孢素A的效果相似。总之,临床相关浓度的丙泊酚对未成熟心脏具有心脏保护作用。