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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Endothelin A and B receptor antagonist bosentan reduces postischemic myocardial injury in the rat: critical timing of administration.
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Endothelin A and B receptor antagonist bosentan reduces postischemic myocardial injury in the rat: critical timing of administration.

机译:内皮素A和B受体拮抗剂波生坦减轻大鼠缺血性心肌损伤:给药的关键时机。

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The purpose of this study was to investigate the effects of bosentan, a mixed endothelin receptor A and B subtype antagonist, on myocardial ischemia-reperfusion injury and to explore the influence of the timing of bosentan administration on its cardioprotective effects. Adult rat hearts were perfused by the Langendorff technique with Krebs-Henseleit solution (KH) at a constant flow rate at 10 mL/min. Global myocardial ischemia was induced by stopping KH perfusion for 40 min, and this was followed by 60 min of reperfusion. Hearts were randomized to 1 of 3 experimental groups (n = 7 each): untreated control; treatment with bosentan 1 micromol/L 10 min prior to, during 40 min global ischemia, and for 15 min of reperfusion (BOS); or treatment with bosentan 1 micromol/L after 15 min of reperfusion (BOS-R). We observed that BOS-R, but not the BOS treatment regimen, significantly reduced the release of cardiac-specific creatine kinase and postischemic myocardial infarct size (P < 0.05 vs. control) without affecting myocardial contractility. Left ventricular developed pressure in the BOS group was significantly (P < 0.01) lower than that in the control group throughout reperfusion. It is concluded that pharmacologically delayed antagonism of endothelin-1 during reperfusion attenuates postischemic myocardial injury. Endothelin-1 antagonist application during early reperfusion may exacerbate postischemic myocardial dysfunction.
机译:这项研究的目的是研究波生坦,一种混合​​的内皮素受体A和B亚型拮抗剂,对心肌缺血-再灌注损伤的作用,并探讨波生坦给药时间对其心脏保护作用的影响。通过Langendorff技术以10 mL / min的恒定流速用Krebs-Henseleit溶液(KH)灌注成年大鼠心脏。通过停止KH灌注40分钟来诱发整体性心肌缺血,然后再灌注60分钟。将心脏随机分为3个实验组中的1个(每组n = 7):未治疗的对照组;在全球缺血40分钟之前,10分钟内以及再灌注(BOS)15分钟之前,用1 micromol / L波生坦治疗;再灌注15分钟后(BOS-R)或用1微摩尔/升的波生坦治疗。我们观察到,BOS-R而非BOS治疗方案可显着减少心脏特异性肌酸激酶的释放和局部缺血后心肌梗死的面积(相对于对照,P <0.05),而不会影响心肌的收缩性。在整个再灌注过程中,BOS组的左心室发育压力显着低于对照组(P <0.01)。结论是在再灌注期间内皮素-1的药理学延迟拮抗作用减弱了缺血后心肌损伤。早期再灌注期间应用内皮素-1拮抗剂可能会加剧缺血后心肌功能障碍。

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