Pagel Paul S, Krolikowski John G
Department of Anesthesiology, The Medical Collegeof Wisconsin, Milwaukee, Wisconsin, USA.
Anesth Analg. 2009 Apr;108(4):1076-82. doi: 10.1213/ane.0b013e318193e934.
Intracellular acidosis during early reperfusion after coronary artery occlusion was recently linked to cardioprotection resulting from myocardial ischemic postconditioning. We tested the hypotheses that transient alkalosis during early reperfusion abolishes helium preconditioning and that the mitochondrial permeability transition pore inhibitor cyclosporin A (CsA) restores the cardioprotective effects of helium during alkalosis in vivo.
Rabbits (n = 36) instrumented for hemodynamics measurement were subjected to a 30-min left anterior descending coronary artery occlusion and 3-h reperfusion. The rabbits received 0.9% saline (control) or three cycles of 70% helium-30% oxygen administered for 5 min interspersed with 5 min of an air-oxygen mixture before left anterior descending coronary artery occlusion in the absence or presence of transient alkalosis (pH = 7.5) produced by administration of IV sodium bicarbonate (10 mEq) 2 min before reperfusion. Other rabbits preconditioned with helium received CsA (5 mg/kg) in the presence of alkalosis or CsA alone.
Helium reduced myocardial infarct size (25% +/- 4% of left ventricular area at risk; P < 0.05) compared with control (44% +/- 6%). Alkalosis during early reperfusion did not alter infarct size alone (46% +/- 2%), but this intervention abolished helium-induced cardioprotection (45% +/- 3%). CsA restored reductions in infarct size produced by helium preconditioning in the presence of alkalosis (28% +/- 6%; P < 0.05 versus control) but did not affect myocardial necrosis alone (43% +/- 6%).
The results demonstrate that transient alkalosis during early reperfusion abolishes helium preconditioning in rabbits. CsA restored helium-induced cardioprotection during alkalosis, suggesting that helium preconditioning inhibits mitochondrial permeability transition pore formation by maintaining intracellular acidosis during early reperfusion.
冠状动脉闭塞后早期再灌注期间的细胞内酸中毒最近被认为与心肌缺血后适应所产生的心脏保护作用有关。我们检验了以下假设：早期再灌注期间的短暂碱中毒会消除氦预处理的作用，并且线粒体通透性转换孔抑制剂环孢素A（CsA）可在体内碱中毒期间恢复氦的心脏保护作用。
对36只安装了血流动力学测量装置的兔子进行30分钟的左前降支冠状动脉闭塞和3小时的再灌注。在左前降支冠状动脉闭塞前，兔子接受0.9%生理盐水（对照组）或三个周期的70%氦 - 30%氧气，每次给予5分钟，期间穿插5分钟的空气 - 氧气混合气体，再灌注前2分钟静脉注射碳酸氢钠（10 mEq）以产生或不产生短暂碱中毒（pH = 7.5）情况。其他经氦预处理的兔子在碱中毒情况下接受CsA（5 mg/kg）或单独接受CsA。
与对照组（44%±6%）相比，氦减少了心肌梗死面积（占左心室危险区域面积的25%±4%；P<0.05）。早期再灌注期间的碱中毒单独并未改变梗死面积（46%±2%），但该干预消除了氦诱导的心脏保护作用（45%±3%）。CsA在碱中毒情况下恢复了氦预处理所产生的梗死面积减少（28%±6%；与对照组相比P<0.05），但单独对心肌坏死无影响（43%±6%）。
结果表明，早期再灌注期间的短暂碱中毒消除了兔子的氦预处理作用。CsA在碱中毒期间恢复了氦诱导的心脏保护作用，提示氦预处理通过在早期再灌注期间维持细胞内酸中毒来抑制线粒体通透性转换孔的形成。
