Role of vagus nerve-muscarinic cholinergic receptor pathway in mitigation of myocardial ischemia-reperfusion injury by intrathecal morphine postconditioning in rats

Abstract

Objective evaluate the role of vagus nerve-muscarinic cholinergic receptor (M receptor) pathway in mitigation of myocardial ischemia-reperfusion (I/R) injury by intrathecal morphine postconditioning in rats. Methods Seventy adult male Sprague-Dawley rats in which intrathecal catheters were successfully placed without complications, weighing 250-350 g, were randomly assigned into 7 groups (n=10 each) using a random number table: sham operation group (Sham group) , I/R group, intrathecal morphine postconditioning group (MP group) , vagal transection (VT) group, VT+ intrathecal morphine postconditioning group (VT+ MP group) , atropine (ATP, M receptor antagonist) + morphine postconditioning group (ATP+ MP group) , and ATP group. Myocardial I/R was produced by occlusion of the anterior descending branch of left coronary artery for 30 min followed by 2 h of reperfusion. Morphine (3 μg/kg, 10 μl) was intrathecally infused over 5 min starting from onset of reperfusion in MP group. Normal saline 10 μl was intrathecally infused over 5 min starting from onset of reperfusion in NS group. The bilateral vagus nerves were transected at 10 min before reperfusion in VT+ MP group. Atropine (0.1 mg/kg, 0.5 ml) was intravenously infused over 5 min starting from 10 min before reperfusion in ATP+ MP group. The occurrence of cardiac arrhythmia (premature ventricular contractions (PVCs) and ventricular tachycardia (VT) /ventricular fibrillation (VF) ) within the first 30 min of reperfusion was recorded. The rats were sacrificed at 120 min of reperfusion, and myocardial specimens were obtained for determination of myocardial infarct size (IS) as a percentage of area at risk (AAR) . IS/AAR ratio was calculated. Results Compared with Sham group, the number of PVCs and VT/VF and IS/AAR ratio were significantly increased in the other groups. Compared with I/R group, the number of PVCs and VT/VF and IS/AAR ratio were significantly decreased in MP group. Compared with MP group, the number of PVCs and VT/VF and IS/AAR ratio were significantly increased in VT+ MP and ATP+ MP groups. Conclusion Vagus nerve-M receptor pathway is involved in mitigation of myocardial I/R injury by intrathecal morphine postconditioning in rats. Key words: Vagus nerves; Receptors, muscarinic; Morphine; Injections, spinal; Myocar-dial reperfusion injury; Ischemic postconditioning