Lehman J D, Dyke C, Abd-Elfattah A, Yeh T, Ding M, Ezrin A, Wechsler A S
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
J Thorac Cardiovasc Surg. 1992 Dec;104(6):1597-601.
Covalent linkage of polyethylene glycol to superoxide dismutase prolongs the serum half-life of the enzyme and may facilitate intracellular access. We tested the myocardial protective effect of polyethylene glycol superoxide dismutase administered once, 24 hours before ischemia. Because hearts were studied ex vivo in a crystalloid perfused system, cardioprotection could be ascribed to intramyocardial or membrane-bound polyethylene glycol superoxide dismutase accumulation. Thirty isolated rabbit hearts from the four following groups were studied: (1) control: untreated rabbits (n = 7); (2) PEG-control: 24-hour intravenous preinfusion of methoxypolyethylene glycol 5000 (5 mg/kg) to examine the effect of polyethylene glycol alone, without conjugation to superoxide dismutase (n = 8); (3) PEG-SOD 10,000: 24-hour preinfusion of polyethylene glycol superoxide dismutase (10,000 U/kg) (n = 8); (4) PEG-SOD 30,000: 24-hour preinfusion of polyethylene glycol superoxide dismutase (30,000 U/kg) (n = 7). After measurement of baseline function with use of an intraventricular balloon, hearts were subjected to normothermic ischemia until a 4 mm Hg rise in intracavitary pressure was observed. Function was assessed at 15-minute intervals throughout reperfusion and expressed as percent return of developed pressure. After 60 minutes of reperfusion, recovery of function was greater for the PEG-SOD 30,000 group (85.6% +/- 2.6%) when compared with either the untreated or PEG-control group (68.9% +/- 2.3% and 71.4% +/- 2.0%, respectively). A similar difference was seen throughout reperfusion. Although an improved return of function was shown in the lower dose PEG-SOD 10,000 group, the margin of difference when compared with any of the control groups was determined to be insignificant at all times of reperfusion and at 60 minutes (75.9% +/- 3.2%). These data demonstrate that high, but not low, doses of polyethylene glycol superoxide dismutase significantly reduce reperfusion injury when administered 24 hours before initiation of global ischemia. Moreover, since the perfusate was superoxide dismutase free, this effect was most likely intramyocardial or membrane bound and therefore might be added to protection afforded by circulating superoxide dismutase.
聚乙二醇与超氧化物歧化酶的共价连接延长了该酶的血清半衰期，并可能有助于其进入细胞内。我们测试了在缺血前24小时一次性给予聚乙二醇化超氧化物歧化酶的心肌保护作用。由于是在离体的晶体灌注系统中研究心脏，心脏保护作用可能归因于心肌内或膜结合的聚乙二醇化超氧化物歧化酶的蓄积。对来自以下四组的30个离体兔心脏进行了研究：（1）对照组：未处理的兔子（n = 7）；（2）聚乙二醇对照组：静脉内预先输注甲氧基聚乙二醇5000（5 mg/kg）24小时，以检查单独的聚乙二醇（未与超氧化物歧化酶结合）的作用（n = 8）；（3）聚乙二醇超氧化物歧化酶10000组：预先输注聚乙二醇化超氧化物歧化酶（10000 U/kg）24小时（n = 8）；（4）聚乙二醇超氧化物歧化酶30000组：预先输注聚乙二醇化超氧化物歧化酶（30000 U/kg）24小时（n = 7）。使用心室内球囊测量基线功能后，心脏进行常温缺血，直至观察到心腔内压力升高4 mmHg。在整个再灌注过程中每隔15分钟评估一次功能，并表示为发育压力恢复的百分比。再灌注60分钟后，聚乙二醇超氧化物歧化酶30000组的功能恢复（85.6%±2.6%）比未处理组或聚乙二醇对照组（分别为68.9%±2.3%和71.4%±2.0%）更好。在整个再灌注过程中都观察到了类似的差异。尽管较低剂量的聚乙二醇超氧化物歧化酶10000组显示功能恢复有所改善，但与任何对照组相比，在再灌注的所有时间点及60分钟时（75.9%±3.2%）差异幅度均被确定为不显著。这些数据表明，在开始全心缺血前24小时给予高剂量而非低剂量的聚乙二醇化超氧化物歧化酶可显著减轻再灌注损伤。此外，由于灌注液中不含超氧化物歧化酶，这种作用很可能是心肌内或膜结合的，因此可能会增强循环超氧化物歧化酶所提供的保护作用。
