Semb A G, Vaage J
Department of Physiology, University of Tromsø, Norway.
Scand J Clin Lab Invest. 1991 Jun;51(4):377-83. doi: 10.1080/00365519109091629.
Inhibitors of the arachidonic acid metabolism (AA) as well as scavengers of oxygen free radicals (OFR) have been shown to reduce myocardial infarct size. We investigated the effects of two inhibitors of AA metabolism on the cardiac effects of OFR. Isolated rat hearts were retrogradely perfused for 10 min with buffer containing hypoxanthine (HX, 1 mmol l-1) and xanthine oxidase (XOD: 24 U l-1) alone (n = 11), or with the addition of ibuprofen (IBU) (n = 6) (a cyclooxygenase inhibitor) or BW 755C (n = 6) (a dual inhibitor of cyclo-oxygenase and lipoxygenase). The hearts were observed for 30 min thereafter (total observation time 40 min). Left-ventricular pressures were measured by a balloon in the left ventricle. HX + XOD significantly reduced left-ventricular developed pressure (LVDP) and coronary flow (CF), but not heart rate. The reduction of LVDP and CF was not significantly ameliorated by the addition of IBU (7.6 x 10(-4) mol l-1) or BW 755C (2 x 10(-3) mmol l-1). OFR increased left-ventricular end-diastolic pressure (LVEDP) from (mean +/- SEM) 0 to 22 +/- 4 mmHg (10 min) and 30 +/- 5 mmHg (40 min). Upon addition of IBU, LVEDP increased from 0 to 24 +/- 8 mmHg and 17 +/- 6 mmHg at 10 and 40 min respectively. The addition of BW 755C almost completely inhibited the increase in LVEDP (1 +/- 1 mmHg and 3 +/- 3 mmHg at 10 min and 40 min). In conclusion, except for inhibition of OFR-induced diastolic dysfunction by BW 755C, neither BW 755C nor IBU appear to inhibit cardiac injury induced by OFR.
花生四烯酸代谢（AA）抑制剂以及氧自由基（OFR）清除剂已被证明可减小心肌梗死面积。我们研究了两种AA代谢抑制剂对OFR心脏效应的影响。将离体大鼠心脏用含次黄嘌呤（HX，1 mmol l-1）和黄嘌呤氧化酶（XOD：24 U l-1）的缓冲液逆行灌注10分钟，单独处理（n = 11），或添加布洛芬（IBU）（n = 6）（一种环氧化酶抑制剂）或BW 755C（n = 6）（一种环氧化酶和脂氧化酶双重抑制剂）。此后观察心脏30分钟（总观察时间40分钟）。通过左心室内的球囊测量左心室压力。HX + XOD显著降低左心室舒张末压（LVDP）和冠状动脉流量（CF），但不影响心率。添加IBU（7.6 x 10(-4) mol l-1）或BW 755C（2 x 10(-3) mmol l-1）并未显著改善LVDP和CF的降低。OFR使左心室舒张末压（LVEDP）从（平均值±标准误）0升高至10分钟时的22±4 mmHg和40分钟时的30±5 mmHg。添加IBU后，LVEDP在10分钟和40分钟时分别从0升高至24±8 mmHg和17±6 mmHg。添加BW 755C几乎完全抑制了LVEDP的升高（10分钟和40分钟时分别为1±1 mmHg和3±3 mmHg）。总之，除了BW 755C可抑制OFR诱导的舒张功能障碍外，BW 755C和IBU似乎均不能抑制OFR诱导的心脏损伤。
