Administration of a CO-releasing molecule at the time of reperfusion reduces infarct size in vivo
Administration of a CO-releasing molecule at the time of reperfusion reduces infarct size in vivo
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DOI：
10.1152/ajpheart.00971.2003
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发表时间：
2004-05-01
影响因子：
4.8
通讯作者：
Bolli, R
中科院分区：
文献类型：
--
作者：
Guo, YR;Stein, AB;Bolli, R
虽然一氧化碳（CO）传统上被视为有毒气体，越来越多的证据表明，它起着重要的稳态和细胞保护作用。然而，其治疗用途受到与CO吸入相关的副作用的限制。最近，过渡金属羰基化合物已被证明是体内运输和释放CO基团的安全有效的手段。本研究的目的是测试水溶性CO释放分子三羰基氯（甘氨酸）钌（II）（CORM-3）在以临床相关方式给予时是否减少体内梗死面积，即，在再灌注的时候。小鼠进行30分钟的冠状动脉闭塞，然后再灌注24小时，并给予CORM-3（3.54 mg/kg，从再灌注前5分钟开始静脉输注60分钟）或等效剂量的无活性CORM-3，其不释放COXOM-3对动脉血压或心率没有影响。对照组和给药组小鼠的风险区域无差异（左心室分别为44.5 +/- 3.5%和36.5 +/- 1.6%）。然而，在治疗的小鼠中梗死面积显著较小[25.8 +/- 4.9%的危险区域（n = 13）对47.7 +/- 3.8%（n = 14），P < 0.05]。CORM-3不会增加血液中的碳氧血红蛋白水平。这些结果表明，一类新的药物，CO释放分子，可用于限制心肌缺血再灌注损伤在体内。
Although carbon monoxide (CO) has traditionally been viewed as a toxic gas, increasing evidence suggests that it plays an important homeostatic and cytoprotective role. Its therapeutic use, however, is limited by the side effects associated with CO inhalation. Recently, transition metal carbonyls have been shown to be a safe and effective means of transporting and releasing CO groups in vivo. The goal of the present study was to test whether a water-soluble CO-releasing molecule, tricarbonylchloro(glycinato) ruthenium (II) (CORM-3), reduces infarct size in vivo when given in a clinically relevant manner, i.e., at the time of reperfusion. Mice were subjected to a 30-min coronary artery occlusion followed by 24 h of reperfusion and were given either CORM-3 (3.54 mg/kg as a 60-min intravenous infusion starting 5 min before reperfusion) or equivalent doses of inactive CORM-3, which does not release CO. CORM-3 had no effect on arterial blood pressure or heart rate. The region at risk did not differ in control and treated mice (44.5 +/- 3.5% vs. 36.5 +/- 1.6% of the left ventricle, respectively). However, infarct size was significantly smaller in treated mice [25.8 +/- 4.9% of the region at risk (n = 13) vs. 47.7 +/- 3.8% (n = 14), P < 0.05]. CORM-3 did not increase carboxyhemoglobin levels in the blood. These results suggest that a novel class of drugs, CO-releasing molecules, can be useful to limit myocardial ischemia-reperfusion injury in vivo.