Dexmedetomidine preconditioning attenuates ischemia/reperfusion injury in isolated rat hearts with endothelial dysfunction
Dexmedetomidine preconditioning attenuates ischemia/reperfusion injury in isolated rat hearts with endothelial dysfunction
复制标题
右美托咪定预处理减轻内皮功能障碍大鼠离体心脏缺血/再灌注损伤
DOI：
10.1016/j.biopha.2019.108837
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发表时间：
2019-06-01
影响因子：
7.5
通讯作者：
Qian, Jinqiao
中科院分区：
文献类型：
--
作者：
He, Liang;Hao, Shuqing;Qian, Jinqiao
背景和目的：右美托咪定预处理（DP）可以模拟药理学预处理，诱导心脏保护作用。冠状动脉内皮细胞在右美托咪定心脏保护中的作用存在争议。在此，我们测试的假设，右美托咪定的保护是不是内皮依赖性的心脏对心肌缺血/再灌注（I/R）injuries.Methods：Langendorff灌注大鼠心脏预处理60 mM的钾产生内皮功能障碍（艾德），然后与右美托咪定，随后进行30分钟的全球缺血，然后再灌注60分钟。为探讨右美托咪定对艾德性心脏病的保护作用，将离体大鼠心脏随机分为假手术组、I/R组、DP组、艾德组、艾德+ I/R组和艾德+ DP + I/R组。评估每颗心脏的心率、左心室功能和冠状动脉灌注压。通过氯化三苯基四氮唑染色评价细胞大小。结果：60 mM氯化钾预处理离体心脏后，冠状动脉内皮细胞对组胺反应的舒张功能明显降低（P < 0.05）。DP可明显缩小I/R所致的左室梗死面积（P < 0.05），降低hs-cTNT（P < 0.05）。此外，右美托咪定预处理大鼠心脏的左心室发展压、+ dp/dt（max）和-dp/dt（max）升高。结论：60 mM钾离子持续灌注10 min可导致离体大鼠心脏发生冠状动脉艾德。右美托咪定对冠状动脉ED心脏I/R损伤具有保护作用，其减轻I/R损伤的作用是非内皮功能依赖性的。
Background and purposes: Dexmedetomidine preconditioning (DP) can mimic pharmacological preconditioning and induce cardiac protection. There are controversies on the roles of coronary endothelia in cardioprotection of dexmedetomidine. Herein, we tested the hypothesis that protection of dexmedetomidine is not endothelial dependent in heart against myocardial ischemia/reperfusion (I/R) injury.Methods: Langendorff-perfused rat hearts were pretreated by 60 mM of potassium to produce endothelial dysfunction (ED), then medicated with dexmedetomidine, and subsequently subjected to 30 min of global ischemia followed by 60 min of reperfusion. To investigate the cardioprotective effect of dexmedetomidine in heart with ED, isolated rat hearts were randomly divided into the following six groups: sham, I/R, DP, ED, ED + I/R, and ED + DP + I/R. Heart rates, left ventricular function, and coronary perfusion pressure were assessed for each heart. Infarct size was evaluated by triphenyltetrazolium chloride staining. High-sensitivity cardiac troponin T (hs-cTNT) of coronary flow perfusion was determined.Results: After the isolated hearts with pretreatment of 60 mM of potassium chloride, diastolic function of coronary endothelia in performance of response to histamine was significantly decreased (P < 0.05). DP attenuated I/R-induced infarct size of the left ventricle (P < 0.05) and decreased hs-cTNT (P < 0.05). Additionally, left ventricular developed pressure, + dp/dt(max), and -dp/dt(max) were elevated in rat hearts pretreated with dexmedetomidine. Furthermore, dexmedetomidine-mediated cardiac protection against I/R injury was still remained in isolated hearts with coronary ED.Conclusion: Continuous perfusion of 60 mM of potassium for 10 min can produce coronary ED in isolated rat hearts. Dexmedetomidine maintains its protective function against I/R injury in heart with coronary ED. Myocardial protection of dexmedetomidine is non-endothelial function dependent in alleviating I/R injury.