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[大鼠急性心肌缺血和再灌注模型中μ和δ阿片受体激动剂抗心律失常活性的比较研究]

[Comparative study of the antiarrhythmic activity of mu- and delta-opioid receptor agonists during acute cardiac ischemia and reperfusion models in rats].

作者信息

Solenkova N V, Maslov L N, Budankova E V, Lishmanov A Iu, Oeltgen P, Govindaswami M, Bespalova Zh D, Ovchinnikov M V, Nagaze H

出版信息

Eksp Klin Farmakol. 2005 Nov-Dec;68(6):25-9.

Abstract

It has been established that pretreatment with the selective mu-opioid receptor (OR) agonist DALDA (0.1 mg/kg, i.v.) or the selective delta1-OR agonists DPDPE (0.09 mg/kg) and/or (-)-TAN-67 (0.08 mg/kg) has no effect on the incidence of ventricular arrhythmias induced by a 10-min coronary artery occlusion and a 10-min reperfusion in ketamine-anesthetized rats. In contrast, the pretreatment with the selective delta2-OR agonist deltorphin II (0.12 mg/kg) and the proposed delta2-OR agonists deltorphin D (0.3 mg/kg) and/or dermorphin H (0.23 mg/kg) increases cardiac resistance to the arrhythmogenic action of acute ischemia and reperfusion. Administration of the mixed mu- and delta-OR agonist dalargin (0.12 mg/kg) 15 min before the coronary artery ligation abolished only the reperfusive ventricular fibrillation. It is concluded that peptidergic stimulation of delta2-ORs can be used as a new means of increasing cardiac tolerance to the arrhythmogenic effects of acute ischemia and reperfusion.

摘要

已经确定,在氯胺酮麻醉的大鼠中,用选择性μ-阿片受体(OR)激动剂DALDA(0.1mg/kg,静脉注射)或选择性δ1-OR激动剂DPDPE(0.09mg/kg)和/或(-)-TAN-67(0.08mg/kg)进行预处理,对10分钟冠状动脉闭塞和10分钟再灌注诱导的室性心律失常的发生率没有影响。相比之下,用选择性δ2-OR激动剂强啡肽II(0.12mg/kg)以及拟用的δ2-OR激动剂强啡肽D(0.3mg/kg)和/或皮啡肽H(0.23mg/kg)进行预处理,可增强心脏对急性缺血和再灌注致心律失常作用的抵抗力。在冠状动脉结扎前15分钟给予μ-和δ-OR混合激动剂达明(0.12mg/kg),仅消除了再灌注性室颤。得出的结论是,对δ2-ORs的肽能刺激可作为一种新方法,用于提高心脏对急性缺血和再灌注致心律失常作用的耐受性。

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