Rabkin S W
Research Center University Hospital (Shaughnessy), University of British Columbia, Vancouver, Canada.
Brain Res Bull. 1993;31(3-4):427-32. doi: 10.1016/0361-9230(93)90236-5.
The purpose of this study was to determine whether the opioid receptor agonist ethylketocyclazocine (EKC) modulates the development of cardiac arrhythmias by an action within the central nervous system. Catecholamine-induced ventricular arrhythmias were produced in the rat by continuous infusion of epinephrine, at incremental doses, until the development of fatal arrhythmias that were usually ventricular fibrillation. EKC, 1 mg/kg, intravenously (IV) significantly (p < 0.05) accentuated the manifestations of or reduced the threshold for epinephrine-induced arrhythmias. The effect of EKC was prevented by the kappa opioid antagonist MR 2266 in a dose-dependent manner. To determine whether the central nervous system is a site of this action of EKC, rats received injection of either EKC or the diluent (control) into the lateral cerebral ventricle (ICV). EKC, 100 and 200 micrograms/kg ICV, significantly (p < 0.05) altered the dose-effect relationship between epinephrine and arrhythmias so that EKC accentuated the development of cardiac arrhythmias. These data indicate that EKC, through an action in the brain, modulates cardiac arrhythmias and suggests a role for opioid receptor agonists, such as EKC, in cardiac arrhythmias and perhaps sudden cardiac death in man.
本研究的目的是确定阿片受体激动剂乙基酮环唑辛（EKC）是否通过中枢神经系统内的作用来调节心律失常的发生。通过递增剂量持续输注肾上腺素，在大鼠中诱发儿茶酚胺诱导的室性心律失常，直至出现通常为室颤的致命性心律失常。静脉注射1mg/kg的EKC显著（p<0.05）加重了肾上腺素诱导的心律失常的表现或降低了其阈值。κ阿片拮抗剂MR 2266以剂量依赖性方式阻断了EKC的作用。为了确定中枢神经系统是否是EKC这种作用的部位，将大鼠的侧脑室（ICV）注射EKC或稀释剂（对照）。脑室内注射100和200μg/kg的EKC显著（p<0.05）改变了肾上腺素与心律失常之间的剂量效应关系，从而使EKC加剧了心律失常的发生。这些数据表明，EKC通过在脑内的作用调节心律失常，并提示阿片受体激动剂如EKC在人类心律失常以及可能的心脏性猝死中发挥作用。
