Non-peptide orphanin receptor antagonist activity in rat myocardial ischemia-induced cardiac arrhythmias

Abstract

One of the causes of sudden cardiac death is arrhythmia after acute myocardial ischemia. After ischemia, endogenous orphanin (N/OFQ) plays a role in the development of arrhythmias. It is discussed in this paper how nonpeptide orphanin receptor (ORL1) antagonists such as J-113397, SB-612111 and compound-24 (C-24) affect arrhythmia in rats following acute myocardial ischemia and what the optimal concentrations for these antagonists are. The electrocardiogram of the rat was recorded as part of the experiment. The concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the myocardium were measured following euthanasia. Following the use of three antagonists, we found the lowest inflammatory factor concentrations and the smallest number of ischemic arrhythmia episodes. All of them had a small impact on cardiac function. LF/HF values were significantly reduced in all three antagonist groups, suggesting that they are involved in the regulation of sympathetic nerves. In conclusion, pretreatment with the three antagonist groups can effectively reduce the concentration of TNF-α and IL-1β, and the occurrence of arrhythmias after ischemia can also be significantly reduced. Inflammation and sympathetic activity may be related to the mechanism of action of antagonists.