Ikeya K, Kashimoto S, Kume M, Kumazawa T
Department of Anesthesia, Kofu Municipal Hospital, Kofu 400-0832.
Masui. 2001 Apr;50(4):365-70.
N-nitro-L-arginine methyl ester (L-NAME) has been reported to have protective action against hydroxyl free radicals. We have investigated whether L-NAME influences free radical formation in the post-ischemic reperfused heart of anesthetized rats. An isolated rat heart-lung preparation was used. Forty male Wistar rats were allocated into D (D-NAME 100 microMol.l-1), L (L-NAME 100 microMol.l-1), LH (L-NAME 100 microMol.l-1 and 1MAC halothane), LI (L-NAME 100 microMol.l-1 and 1MAC isoflurane), and LS (L-NAME 100 microMol.l-1 and 1MAC sevoflurane) groups. The heart was perfused initially at the cardiac output of 30 ml.min-1 and the atrial pressure of 70 mmHg. Drugs were administered into the reservor 7 min after the start of perfusion. Ten minutes after the start of perfusion, the heart was rendered globally ischemic for 10 min by reducing the preload and afterload to zero and then reperfused for 10 min. At the end of reperfusion, the heart was freeze-dried for 4 days. The perfusate blood was collected just before and after ischemia and at the end of reperfusion. The formation of hydroxyl radicals in the perfusate blood and heart was measured with high-performance liquid chromatography using salicylic acid. Hydroxyl radicals react with salicylic acid, yielding dihydroxybenzoic acid (DHBA). Before and after ischemia, there were no significant differences among the groups in cardiac output, systolic pressure, heart rate, and right atrial pressure. DHBAs in the heart of L, LH, LI, and LS groups were significantly lower than those of D group. However, there were no differences in the DHBA levels among 4 groups. The concentrations of DHBA in the perfusate blood after ischemia and reperfusion were significantly higher than those before ischemia in all groups. DHBAs in the perfusate blood after ischemia and reperfusion of L, LH, LI, and LS groups were significantly lower than those of D group. However, there were no differences in the DHBA levels among 4 groups administered L-NAME. This study indicates that L-NAME reduces hydroxyl free radical formation in the post-ischemic reperfused heart in anesthetized rats and volatile anesthetics do not influence the depressant effect of hydroxyl free radical formation by L-NAME.
据报道,N-硝基-L-精氨酸甲酯(L-NAME)对羟基自由基具有保护作用。我们研究了L-NAME是否会影响麻醉大鼠缺血再灌注心脏中的自由基形成。使用离体大鼠心肺制备物。将40只雄性Wistar大鼠分为D组(D-NAME 100微摩尔/升)、L组(L-NAME 100微摩尔/升)、LH组(L-NAME 100微摩尔/升和1MAC氟烷)、LI组(L-NAME 100微摩尔/升和1MAC异氟烷)和LS组(L-NAME 100微摩尔/升和1MAC七氟烷)。心脏最初以每分钟30毫升的心输出量和70毫米汞柱的心房压力进行灌注。在灌注开始7分钟后将药物注入储液器。灌注开始10分钟后,通过将前负荷和后负荷降至零使心脏全局缺血10分钟,然后再灌注10分钟。再灌注结束时,将心脏冷冻干燥4天。在缺血前后以及再灌注结束时收集灌注血液。使用水杨酸通过高效液相色谱法测量灌注血液和心脏中羟基自由基的形成。羟基自由基与水杨酸反应,生成二羟基苯甲酸(DHBA)。缺血前后,各组在心输出量、收缩压、心率和右心房压力方面无显著差异。L组、LH组、LI组和LS组心脏中的DHBA明显低于D组。然而,4组之间的DHBA水平没有差异。所有组缺血和再灌注后灌注血液中DHBA的浓度明显高于缺血前。L组、LH组、LI组和LS组缺血和再灌注后灌注血液中的DHBA明显低于D组。然而,给予L-NAME的4组之间的DHBA水平没有差异。本研究表明,L-NAME可减少麻醉大鼠缺血再灌注心脏中羟基自由基的形成,挥发性麻醉剂不影响L-NAME对羟基自由基形成的抑制作用。