MARKED REDUCTION IN MYOCARDIAL INFARCT SIZE DUE TO PROLONGED INFUSION OF AN ANTIOXIDANT DURING REPERFUSION
MARKED REDUCTION IN MYOCARDIAL INFARCT SIZE DUE TO PROLONGED INFUSION OF AN ANTIOXIDANT DURING REPERFUSION
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DOI：
10.1161/01.cir.89.4.1792
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发表时间：
1994-04-01
期刊：
影响因子：
37.8
通讯作者：
KONG, Y
中科院分区：
文献类型：
--
作者：
HORWITZ, LD;FENNESSEY, PV;KONG, Y
背景心肌梗死后早期再灌注是否会引起由活性氧介导的进一步坏死或其他机制一直存在争议。明确的证据表明，只有在再灌注过程中给予治疗药物可以预防，而不是延迟或修改，损伤已经稀少。未能解释变量，如侧支血流，独立影响梗死面积，并试图在再灌注中过早测量梗死面积，可能限制了以前一些研究的灵敏度和特异性。我们检测了静脉输注N-（2-巯基丙酰基）-甘氨酸（MPG）（一种可扩散的抗氧化剂）对梗死面积的影响。采用氯化三苯基四氮唑和伊文思蓝双重灌注法测量心肌梗死面积和危险区域，放射性微球法测量局部心肌血流量。输注MPG 100 mg.kg（-1）.h（-1），在再灌注开始前15分钟或再灌注开始后30分钟开始，持续至再灌注4小时，然后肌肉注射，可使梗死面积减少，危险区域和侧支血流水平分别标准化60%和45%。当MPG的输注仅限于缺血的最后15分钟和再灌注的第一小时时，标准化的梗死面积减少了26%。心率、血压及其乘积在所研究的四组之间没有差异。MPG的血浆半衰期为
Background There has been controversy about whether early reperfusion of myocardial infarcts causes further necrosis mediated by reactive oxygen species or other mechanisms. Unequivocal evidence that therapeutic agents given only during reperfusion can prevent, rather than delay or modify, injury has been sparse. Failure to account for variables, such as collateral blood flow, that influence infarct size independently and attempts to measure infarct size too early in reperfusion may have limited the sensitivity and specificity of some previous studies.Methods and Results After 90 minutes of coronary occlusion and 48 hours of reperfusion in a canine model, we examined the effect on infarct size of intravenous infusion of N-(2-mercaptopropionyl)-glycine (MPG), a diffusible antioxidant. Infarct size and region at risk were measured by postmortem dual perfusion with triphenyl tetrazolium chloride and Evans blue dyes, and regional myocardial blood flow was measured with radioactive microspheres. Infusion of MPG 100 mg.kg(-1).h(-1), beginning either 15 minutes before the onset of reperfusion or 30 minutes after the onset of reperfusion and continued until 4 hours of reperfusion and followed by an intramuscular dose, reduced infarct size, normalized for both region at risk and the level of collateral blood flow, by 60% and 45%, respectively. When infusion of MPG was limited to the last 15 minutes of ischemia and the first hour of reperfusion only, the normalized infarct size was reduced by 26%. Heart rate, blood pressure, and their product did not differ among the four groups studied. The plasma half-time of MPG was