Antiarrhythmic effect of U50,488H on isolated rat heart in vitro

AIM: To investigate the effect of U50, 488H (a selective к-opioid receptor agonist) and noradrenalin (NE, an adrenergic receptor agonist) on ventricular arrhythmias induced by myocardial ischemia and reperfusion in rats in vitro. METHODS: Rats were randomly divided into 5 groups (7 rats in each group), i.e., normal control group, ischemia/reperfusion group (I/R), U50,488H+I/R group, NE+I/R group, U50,488H+NE+I/R group. The isolated heart was perfused by using Langendorff equipment and the front branch of coronary artery was ligated for 20 min, and then the perfusion was resumed for 20 min to engender the I/R condition. U50,488H(5×10 -6 mol/L) and NE(1×10 -7 mol/L) were used to interfere the effects during myocardial ischemia and reperfusion. Heart rate (HR), arterial blood pressure (ABP), left ventricular pressure (LVP), cardiac function (±dp/dtmax), rate of ventricular tachycardia (VT) and ventricular fibrillation (VF) were determined in rats. RESULTS: ① Every index of the heart functions decreased significantly, and HR increased after myocardial ischemia. With myocardial reperfusion, the condition was improved a little. Compared with I/R group, HR decreased significantly with U50, 488H administration (P0.05). ② Compared with normal control group and I/R group, the incidence of ventricular arrhythmias and arrhythmia score were enhanced in I/R+NE group (P0.01). However, it showed that not only the incidence of VT and VF score during myocardial ischemia and reperfusion and ventricular arrhythmias and arrhythmia score of I/R group, but also ventricular arrhythmias and arrhythmia score of I/R+NE group decreased significantly with administration of U50,488H (P0.01). CONCLUSION: к-opioid receptor agonist U50,488H antagonizes the arrhythmias induced by NE during myocardial ischemia and reperfusion.