Inhaled nitric oxide decreases infarction size and improves left ventricular function in a murine model of myocardial ischemia-reperfusion injury
Inhaled nitric oxide decreases infarction size and improves left ventricular function in a murine model of myocardial ischemia-reperfusion injury
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DOI：
10.1152/ajpheart.01172.2005
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发表时间：
2006-07-01
影响因子：
4.8
通讯作者：
Scherrer-Crosbie, Marielle
中科院分区：
文献类型：
--
作者：
Hataishi, Ryuji;Rodrigues, Ana Clara;Scherrer-Crosbie, Marielle
为了了解吸入一氧化氮(NO)是否能减轻心肌缺血再灌注(I/R)损伤，我们研究了一种小鼠心肌梗死(MI)模型。麻醉小鼠结扎冠状动脉左前降支30、60或120min，然后再灌流。小鼠于再灌流前20min开始不呼吸，持续24 h，测量心肌梗死面积和危险面积，超声心动图和有创血流动力学检测左心功能。吸入40或80ppm，而不是20ppm的NO，可降低MI大小与危险面积的比率。再灌流后24 h超声心动图评价吸入NO可改善左心室收缩功能，再灌流72 h后血流动力学评价左心室收缩和舒张期功能。吸入NO的小鼠心肌中性粒细胞浸润减少，中性粒细胞耗竭可阻止吸入NO减轻心肌I/R损伤。吸入NO可增加动脉亚硝酸盐水平，但不改变心肌cGMP水平。呼吸40ppm或80ppm的NO可显著缩小小鼠缺血再灌流后的心肌梗死面积，改善心功能。吸入NO可能是挽救I/R损伤风险心肌的一种新方法。
To learn whether nitric oxide ( NO) inhalation can decrease myocardial ischemia-reperfusion ( I/R) injury, we studied a murine model of myocardial infarction ( MI). Anesthetized mice underwent left anterior descending coronary artery ligation for 30, 60, or 120 min followed by reperfusion. Mice breathed NO beginning 20 min before reperfusion and continuing thereafter for 24 h. MI size and area at risk were measured, and left ventricular ( LV) function was evaluated using echocardiography and invasive hemodynamic measurements. Inhalation of 40 or 80 ppm, but not 20 ppm, NO decreased the ratio of MI size to area at risk. NO inhalation improved LV systolic function, as assessed by echocardiography 24 h after reperfusion, and systolic and diastolic function, as evaluated by hemodynamic measurements 72 h after reperfusion. Myocardial neutrophil infiltration was reduced in mice breathing NO, and neutrophil depletion prevented inhaled NO from reducing myocardial I/R injury. NO inhalation increased arterial nitrite levels but did not change myocardial cGMP levels. Breathing 40 or 80 ppm NO markedly and significantly decreased MI size and improved LV function after ischemia and reperfusion in mice. NO inhalation may represent a novel method to salvage myocardium at risk of I/R injury.