Hoffmeister H M, Fischer M, Kazmaier S, Heller W, Seipel L
Department of Cardiology, Center for Internal Medicine, Eberhard-Karls University, Tübingen, Germany.
Thorac Cardiovasc Surg. 1999 Apr;47(2):88-93. doi: 10.1055/s-2007-1013117.
The protease inhibitor aprotinin has been reported to have an anti-ischemic effect on left-ventricular myocardium in patients undergoing cardiopulmonary bypass operation. To examine the anti-ischemic properties beside its antifibrinolytic and inhibitory action on the kallikrein-bradykinin system, we investigated this substance in buffer-perfused rat hearts.
24 isolated isovolumically contracting rat hearts received a 10-minute infusion of either 10000 units aprotinin or pure saline followed by 30 minutes of no-flow global ischemia and 45 minutes of reperfusion. Hemodynamics, high-energy phosphates, and troponin T as molecular marker of cardiac injury were studied.
During 15 minutes of reperfusion steady state function was identical in both groups, with a recovery of the developed left-ventricular pressure to 81.9+/-1.5% after protease inhibition and 83.0+/-2.6% in the controls. Coronary flow, myocardial oxygen consumption, and contractile reserve after maximum Ca++ stimulation were also identical. High-energy phosphates were comparably reduced in both groups (adenine nucleotides: 3.1+/-0.3 micromol/g ww after aprotinin vs. controls 2.7+/-0.4 micromol/g ww and creatine phosphate: 6.5+/-0.9 micromol/g ww vs. controls 4.7+/-1.1 micromol/g ww). However, release of the cardiac specific marker troponin T was lower after ischemia at several measurements (p<0.05). The total release of troponin T was 44+/-10 ng in the aprotinin treated hearts vs. 90+/-17 ng in the postischemic control hearts (p<0.05).
The findings demonstrate that aprotinin in a moderate dose is effective in reducing postischemic troponin release in a non-blood perfused system. Measurement of myocardial high-energy phosphates after aprotinin use was performed for the first time and indicates that not a reduction in severity of direct myocardial ischemic intensity but a beneficial action on processes causing release of troponin is the mode of action of this effect.
据报道，蛋白酶抑制剂抑肽酶对接受体外循环手术患者的左心室心肌具有抗缺血作用。为了研究其除抗纤维蛋白溶解和对激肽释放酶 - 缓激肽系统的抑制作用之外的抗缺血特性，我们在缓冲液灌注的大鼠心脏中对该物质进行了研究。
24只离体等容收缩的大鼠心脏接受10分钟的10000单位抑肽酶或纯生理盐水输注，随后进行30分钟的无血流全心缺血和45分钟的再灌注。研究了血流动力学、高能磷酸盐以及作为心脏损伤分子标志物的肌钙蛋白T。
在再灌注15分钟时，两组的稳态功能相同，蛋白酶抑制后左心室舒张末压恢复至81.9±1.5%，对照组为83.0±2.6%。冠状动脉血流、心肌耗氧量以及最大钙刺激后的收缩储备也相同。两组的高能磷酸盐均有类似程度的降低（腺嘌呤核苷酸：抑肽酶处理后为3.1±0.3微摩尔/克湿重，对照组为2.7±0.4微摩尔/克湿重；磷酸肌酸：分别为6.5±0.9微摩尔/克湿重和4.7±1.1微摩尔/克湿重）。然而，在几次测量中，缺血后心脏特异性标志物肌钙蛋白T的释放较低（p<0.05）。抑肽酶处理的心脏中肌钙蛋白T的总释放量为44±10纳克，缺血后对照组心脏为90±17纳克（p<0.05）。
研究结果表明，中等剂量的抑肽酶在非血液灌注系统中可有效减少缺血后肌钙蛋白的释放。首次在使用抑肽酶后测量心肌高能磷酸盐，表明该效应的作用方式不是降低直接心肌缺血强度的严重程度，而是对导致肌钙蛋白释放的过程产生有益作用。
