Quantification of hydroxyl radical and its lack of relevance to myocardial injury during early reperfusion after graded ischemia in rat hearts.
Quantification of hydroxyl radical and its lack of relevance to myocardial injury during early reperfusion after graded ischemia in rat hearts.
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DOI：
10.1161/01.res.71.1.96
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发表时间：
1992-07
影响因子：
20.1
通讯作者：
G. Takemura;T. Onodera;M. Ashraf
中科院分区：
文献类型：
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作者：
G. Takemura;T. Onodera;M. Ashraf
为了阐明羟基自由基（.OH）在心脏缺血后再灌注过程中的病理生理作用，我们测量了离体灌流大鼠心脏在不同缺血间隔5，10，15，20，30和60分钟后30分钟再灌注期间冠状动脉流出物中的.OH产物。使用水杨酸作为.OH的探针，并使用具有紫外检测的高效液相色谱法对其衍生物2，5-二羟基苯甲酸（2，5-DHBA）进行定量。2，5-DHBA在非缺血心脏的流出液中可以忽略不计，但在缺血10分钟或更长时间的心脏中检测到显著量。各组2，5-DHBA的峰值均出现在再灌注开始后90秒内。2，5-DHBA的累积量在缺血15分钟组中最大（再灌注30分钟后为6.73 +/- 1.04 nmol/g心脏湿重）;随着缺血时间的延长，2，5-DHBA的累积量减少，在缺血60分钟组中，再灌注30分钟后为2.38 +/- 0.84 nmol/g心脏湿重。在15分钟缺血/30分钟再灌注模型中，2，5-DHBA的累积量与功能恢复（+/- dP/dt、心率和冠状动脉流量）、乳酸脱氢酶释放和形态学损伤之间没有相关性。尽管用0.5 mM去铁胺（一种铁螯合剂）治疗显著降低了2，5-DHBA（再灌注30分钟后从6.73 +/- 1.04降至2.29 +/- 0.80 nmol/g湿重，p <0.01），但它未能减少缺血15分钟组的缺血后心肌损伤。结果表明，.OH的产生是由先前的缺血间隔的影响和.OH不施加一个立即的直接影响缺血后的损伤在早期再灌注在离体灌注大鼠心脏，虽然仍然存在一种可能性，水杨酸捕获的小部分.OH可能不密切相关的心肌损伤。
To elucidate the pathophysiological role of the hydroxyl radical (.OH) during the postischemic reperfusion of the heart, we measured the .OH product in the coronary effluent from isolated perfused rat heart during a 30-minute reperfusion period after various ischemic intervals of 5, 10, 15, 20, 30, and 60 minutes. Salicylic acid was used as the probe for .OH, and its derivative, 2,5-dihydroxybenzoic acid (2,5-DHBA), was quantified using high-performance liquid chromatography with ultraviolet detection. 2,5-DHBA was negligible in the effluent from nonischemic hearts, but a significant amount was detected from the hearts rendered ischemic for 10 minutes or longer. The peak of 2,5-DHBA was seen within 90 seconds after the onset of reperfusion in every group. The accumulated amount of 2,5-DHBA was maximal in the group with 15-minute ischemia (6.73 +/- 1.04 nmol/g wet heart wt after 30 minutes of reperfusion); it decreased as the ischemic time was prolonged and was 2.38 +/- 0.84 nmol/g wet wt after 30 minutes of reperfusion in the group with 60-minute ischemia. In the model of 15-minute ischemia/30-minute reperfusion, there was no correlation between the accumulated amount of 2,5-DHBA and functional recovery (+/- dP/dt, heart rate, and coronary flow), lactate dehydrogenase release, and morphological damage. Although treatment with 0.5 mM deferoxamine, an iron chelator, significantly decreased 2,5-DHBA (from 6.73 +/- 1.04 to 2.29 +/- 0.80 nmol/g wet wt after 30 minutes of reperfusion, p less than 0.01), it failed to reduce the postischemic myocardial injury in the group with 15-minute ischemia. The results suggest that .OH production is influenced by the preceding ischemic interval and that .OH does not exert an immediate direct effect on postischemic damage during early reperfusion in the isolated perfused rat heart, although a possibility remains that the small portion of .OH trapped by salicylic acid may not be intimately associated with myocardial injury.