Shirato C, Miura T, Ooiwa H, Toyofuku T, Wilborn W H, Downey J M
Department of Physiology, University of South Alabama, Mobile 36688.
J Mol Cell Cardiol. 1989 Nov;21(11):1187-93. doi: 10.1016/0022-2828(89)90695-0.
We tested the ability of a single dose of superoxide dismutase to induce salvage of reperfused rabbit myocardium. Infarct size was measured by tetrazolium method following 3, 24, or 72 h of reperfusion. In addition, the 24 h reperfused hearts were examined to determine if the drug induced salvage in those hearts was reflected in the histology. A coronary arterial branch was occluded for 45 min and then allowed to reperfuse for 3, 24 or 72 h. At the end of the reperfusion period the hearts were removed, perfusion stained with triphenyl tetrazolium, and fixed in buffered formalin. The hearts were sectioned and infarct size was determined in all groups. In addition, the 24 h heart slices were prepared for histology with H&E staining. The results revealed that 5 mg/kg hSOD treatment was associated with smaller infarcts in the 3 and 24 h groups but that differences were no longer apparent in the 72 h group. The 24 h control hearts showed good correlation between infarct size by TTC and that by conventional histology. In the 24 h treatment hearts, however, infarcts by TTC averaged only about 1/2 the size of those by conventional histology. We conclude that a single dose of hSOD fails to offer a sustained reduction of infarct size. Furthermore, histology from the 24 h reperfused group revealed that hSOD did not delay the onset of necrosis but rather simply caused dead tissue to retain its ability to reduce the tetrazolium salts.
我们测试了单剂量超氧化物歧化酶诱导兔再灌注心肌挽救的能力。在再灌注3、24或72小时后,采用四氮唑法测量梗死面积。此外,对再灌注24小时的心脏进行检查,以确定药物诱导的心肌挽救是否在组织学上有所体现。将冠状动脉分支闭塞45分钟,然后再灌注3、24或72小时。在再灌注期结束时,取出心脏,用三苯基四氮唑进行灌注染色,然后固定在缓冲福尔马林中。将心脏切片并确定所有组的梗死面积。此外,将再灌注24小时的心脏切片用苏木精和伊红染色以进行组织学检查。结果显示,5mg/kg人超氧化物歧化酶治疗使3小时和24小时组的梗死面积减小,但在72小时组中差异不再明显。24小时对照组心脏通过四氮唑染色法测得的梗死面积与传统组织学方法测得的梗死面积具有良好的相关性。然而,在24小时治疗组的心脏中,通过四氮唑染色法测得的梗死面积平均仅为传统组织学方法测得的梗死面积的约二分之一。我们得出结论,单剂量人超氧化物歧化酶不能持续减小梗死面积。此外,再灌注24小时组的组织学检查显示,人超氧化物歧化酶并未延迟坏死的发生,而只是使坏死组织保持其还原四氮唑盐的能力。