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用别嘌呤醇和超氧化物歧化酶控制氧细胞毒性:犬全心肌缺血-再灌注损伤模型

Control of oxygen cytotoxicity with allopurinol and superoxide dismutase: a canine model of global myocardial ischemia-reperfusion injury.

作者信息

Qayumi A K, Jamieson W R, Rosado L J, McConville B, Chow V D

机构信息

Department of Surgery, University of British Columbia, Vancouver, Canada.

出版信息

J Invest Surg. 1997 Jan-Apr;10(1-2):63-8. doi: 10.3109/08941939709032128.

DOI:10.3109/08941939709032128
PMID:9100178
Abstract

The purpose of this study was to assess the effects of acute pharmacological interventions on the ischemia-reperfusion damage in a canine model of hypothermic global myocardial ischemia. Three experimental groups each consisting of seven animals were subjected to 2 h of global ischemia followed by 1 h of reperfusion. Group A (control) used Tyers' iso-osmolar potassium cardioplegia solution; group B received allopurinol (40 mg/kg), 95% intravenously (IV) systemically with 5% added to the final infusion of Tyers' solution. In group C, superoxide dismutase (6.5 mg/kg) was used, one third of the total dose in the final delivery of the Tyers' cardioplegia solution and two thirds IV during the initial 5 min of reperfusion. In all three groups, myocardial temperature was maintained between 15 and 19 degrees C. Methods of evaluation included hemodynamic and echocardiographic parameters of ventricular function. Assessment was performed at three time periods: pre-cardiopulmonary bypass (control), 60 min postreperfusion and immediately post-volume loading (at 2 h after cardiopulmonary bypass). No significant deterioration of myocardial function was observed in either of the experimental groups after the use of these preservation techniques. Comparison of regression slopes based on analysis of covariance for myocardial performance, systolic function, and diastolic compliance did not demonstrate any significant differences between the groups. Two hours of global ischemia was not sufficient to cause measurable damage to the myocardium on the basis of which the pharmacological intervention with allopurinol and superoxide dismutase could be evaluated. The controversy surrounding the use of allopurinol and superoxide dismutase is discussed with the findings of this experimental protocol and is brought up for scientific dialogue.

摘要

本研究的目的是评估急性药物干预对低温性全心肌缺血犬模型缺血再灌注损伤的影响。三个实验组,每组七只动物,经历2小时全心缺血,随后1小时再灌注。A组(对照组)使用泰尔斯等渗钾心脏停搏液;B组接受别嘌呤醇(40mg/kg),95%经静脉全身给药,5%加入泰尔斯溶液的最终输注液中。C组使用超氧化物歧化酶(6.5mg/kg),总剂量的三分之一在泰尔斯心脏停搏液的最终给药时使用,三分之二在再灌注开始的5分钟内经静脉给药。在所有三组中,心肌温度维持在15至19摄氏度之间。评估方法包括心室功能的血流动力学和超声心动图参数。在三个时间段进行评估:体外循环前(对照)、再灌注后60分钟和容量负荷后即刻(体外循环后2小时)。使用这些保存技术后,在任何一个实验组中均未观察到心肌功能的显著恶化。基于协方差分析对心肌性能、收缩功能和舒张顺应性的回归斜率比较未显示各组之间有任何显著差异。两小时的全心缺血不足以对心肌造成可测量的损伤,因此无法评估别嘌呤醇和超氧化物歧化酶的药物干预效果。结合本实验方案的结果讨论了围绕别嘌呤醇和超氧化物歧化酶使用的争议,并提出进行科学对话。

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