Hatori N, Tadokoro H, Satomura K, Miyazaki A, Fishbein M C, Rydén L, Corday E, Drury J K
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
Eur Heart J. 1991 Mar;12(3):442-50. doi: 10.1093/oxfordjournals.eurheartj.a059915.
The efficacy of coronary venous versus left atrial administration of superoxide dismutase was studied in 24 open chest pigs which had 60 min of left anterior descending coronary artery occlusion followed by 3 h reperfusion. The pigs were randomly assigned to three treatment protocols: group A (n = 8) superoxide dismutase (5 mg kg-1) was infused into the great cardiac vein for 30 min beginning 15 min before reperfusion; group B (n = 8) superoxide dismutase (5 mg kg-1) was infused into the left atrium in a similar manner to group A; group C (n = 8) bovine serum albumin (5 mg kg-1) was infused into the great cardiac vein in the same manner as group A. Infarct size, expressed as percent of area at risk, was significantly smaller in group A (28.2 +/- 13.0%) than groups B (58.7 +/- 8.3%) and C (61.6 +/- 7.2%) (P less than 0.05). The results indicate that retroinfusion of superoxide dismutase into the great cardiac vein before reperfusion may be an effective treatment for the prevention of reperfusion injury, even in the absence of a well developed coronary collateral circulation. Antegrade (left atrial) administration of the same amount of superoxide dismutase did not decrease infarct size in pigs. The most likely explanation for this difference in efficacy is that drug delivery with left atrial administration is dependent on antegrade flow with reperfusion which is less reliable and less efficient than coronary venous retroinfusion. The latter provides a predictably high concentration of superoxide dismutase to the jeopardized myocardium during the period of ischaemia before reperfusion.
在24只开胸猪身上研究了冠状静脉与左心房注射超氧化物歧化酶的疗效,这些猪经历了60分钟的左前降支冠状动脉闭塞,随后再灌注3小时。猪被随机分为三种治疗方案:A组(n = 8)在再灌注前15分钟开始,将超氧化物歧化酶(5 mg kg-1)注入大冠状静脉30分钟;B组(n = 8)以与A组相似的方式将超氧化物歧化酶(5 mg kg-1)注入左心房;C组(n = 8)以与A组相同的方式将牛血清白蛋白(5 mg kg-1)注入大冠状静脉。以危险区域面积的百分比表示的梗死面积,A组(28.2 +/- 13.0%)显著小于B组(58.7 +/- 8.3%)和C组(61.6 +/- 7.2%)(P < 0.05)。结果表明,在再灌注前将超氧化物歧化酶逆行注入大冠状静脉可能是预防再灌注损伤的有效治疗方法,即使在没有完善的冠状动脉侧支循环的情况下也是如此。在猪身上,等量的超氧化物歧化酶顺行(左心房)给药并没有减小梗死面积。这种疗效差异最可能的解释是,左心房给药的药物输送依赖于再灌注时的顺行血流,这比冠状静脉逆行灌注更不可靠且效率更低。后者在再灌注前的缺血期为濒危心肌提供了可预测的高浓度超氧化物歧化酶。