Hatori N, Uriuda Y, Yoshizu H, Shimizu M, Tanaka S
Department of Surgery, II, National Defense Medical College, Tokorozawa, Japan.
Nihon Kyobu Geka Gakkai Zasshi. 1990 Jul;38(7):1118-27.
To determine the efficacy of direct versus systemic administration of human recombinant superoxide dismutase (rt-SOD) in acute myocardial ischemia and reperfusion, the following experimental model was applied. Twenty-one dogs were subjected to 30 minutes normothermic global ischemia caused by the occlusion of the ascending aorta followed by 60 minutes reperfusion. To eliminate collateral blood flows during the ischemia, bipulmonary hilus were cross clamped. The dogs were randomly assigned to three groups: group A (n = 7), 12 ml of normal saline was injected through the aortic root into the coronary artery 1 minute prior to reperfusion, in addition to a 30 minute continuous infusion of 50 ml of saline into the cardiopulmonary bypass circuit beginning just after reperfusion; group B (n = 7), rt-SOD (10,000 U/kg) dissolved in 12 ml saline was administered by bolus injection through the aortic root and an additional 30,000 U/kg of rt-SOD dissolved in 50 ml of saline was injected into the cardiopulmonary bypass circuit as the same manner as the group A; group C (n = 7), the treatment was similar to the group B except the bolus injection of rt-SOD was into the cardiopulmonary bypass circuit. The left ventricular stroke work index (LVSWI) was determined by a right heart bypass technique and expressed as a percent recovery of pre-occlusion state. Morphologic structures were observed by the electron microscope. The coronary sinus blood was assessed for malondialdehyde (MDA) measured by TBA method and creatine phosphokinase (CPK). The percent of recovery of LVSWI after 60 minutes reperfusion was superior in group B (121 +/- 82%) than groups A (24 +/- 38%*, p less than 0.05) and C (52 +/- 21%). In group B, the myocardial cell structure had a normal appearance in most areas, but swollen mitochondria and disrupted myofibrils were observed in groups A and C. Serum MDA levels did not change in all groups. Increasing CPK levels after reperfusion were less in group b than group A. These results suggest that an adequate concentration of rt-SOD in the interstitial fluid or cell surface at the time of reperfusion may be required to prevent reperfusion injury.
为了确定人重组超氧化物歧化酶（rt-SOD）直接给药与全身给药在急性心肌缺血及再灌注中的疗效，采用了以下实验模型。21只犬接受30分钟的常温全心缺血，通过升主动脉阻断造成，随后再灌注60分钟。为了消除缺血期间的侧支血流，双侧肺门进行交叉钳夹。犬被随机分为三组：A组（n = 7），在再灌注前1分钟经主动脉根部向冠状动脉注射12 ml生理盐水，此外，在再灌注后立即开始在体外循环回路中持续输注50 ml生理盐水30分钟；B组（n = 7），将溶解于12 ml生理盐水中的rt-SOD（10,000 U/kg）经主动脉根部推注给药，另外将溶解于50 ml生理盐水中的30,000 U/kg rt-SOD以与A组相同的方式注入体外循环回路；C组（n = 7），治疗方法与B组相似，只是rt-SOD的推注是注入体外循环回路。左心室每搏作功指数（LVSWI）通过右心旁路技术测定，并表示为缺血前状态恢复的百分比。通过电子显微镜观察形态结构。用TBA法测定冠状窦血中的丙二醛（MDA）和肌酸磷酸激酶（CPK）。再灌注60分钟后，B组的LVSWI恢复百分比（121±82%）优于A组（24±38%*，p＜0.05）和C组（52±21%）。在B组中，大多数区域的心肌细胞结构外观正常，但在A组和C组中观察到线粒体肿胀和肌原纤维破坏。所有组的血清MDA水平均未改变。再灌注后B组CPK水平的升高低于A组。这些结果表明，再灌注时间质液或细胞表面需要有足够浓度的rt-SOD以预防再灌注损伤。
