ABSTRACT
Objective evaluate the role of vagus nerve?muscarinic cholinergic receptor ( M recep?tor) pathway in mitigation of myocardial ischemia?reperfusion (I∕R) injury by intrathecal morphine postcon?ditioning in rats. Methods Seventy adult male Sprague?Dawley rats in which intrathecal catheters were suc?cessfully 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 postcondi?tioning 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 ( 3μg∕kg, 10μl) was in?trathecally infused over 5 min starting from onset of reperfusion in MP group. Normal saline 10 μl was in?trathecally 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 ar? rhythmia ( premature ventricular contractions ( PVCs) and ventricular tachycardia ( VT)∕ventricular fibrilla?tion ( VF) ) within the first 30 min of reperfusion was recorded. The rats were sacrificed at 120 min of reper?fusion, and myocardial specimens were obtained for determination of myocardial infarct size ( IS) as a per?centage 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 in?creased in VT+MP and ATP+MP groups. Conclusion Vagus nerve?M receptor pathway is involved in miti?gation of myocardial I∕R injury by intrathecal morphine postconditioning in rats.
ABSTRACT
Objective To evaluate the role of nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signal transduction pathway in mitigation of myocardial ischemia-reperfusion injury by intrathecal morphine postconditioning in rats.Methods Forty-eight male Sprague-Dawley rats in which intrathecal catheters were successfully placed without complications,weighing 250-350 g,were randomly assigned into 8 groups (n =6 each):normal saline group (NS group),morphine postconditioning group (Mp group),1-NG-nitroarginine methyl ester (L-NAME,NO synthase inhibitor) + morphine postconditioning group (L-NAME + MP group),ODQ (guanylate cyclase inhibitor) + morphine postconditioning group (ODQ + MP group),KT5823 (PKG inhibitor) + morphine postconditioning group (KT5823 + MP group),L-NAME group,ODQ group and KT5823 group.Myocardial ischemia was induced by 30 min of occlusion of anterior descending branch of left coronary artery followed by 2 h of reperfusion.At 25 rin of ischemia,normal saline 10 μl was intrathecally infused over 5 min in group NS,and morphine (3 μg/kg,10 μl) was intrathecally infused over 5 min in group MP.L-NAME (30 nmol,10 μl),ODQ (11 nmol,10 μl) and KT5823 (20 pmol,10 μl) were intrathecally injected at 10 rin before morphine postconditioning in L-NAME + MP,ODQ + MP and KT5823 + MP groups,respectively.Before myocardial ischemia (T0),at 25 and 30 min of ischemia (T1-2),and at 120 min of reperfusion (T3),MAP and HR were recorded,and rate-pressure product (RPP) was calculated.The rats were sacrificed at T3,and myocardial specimens were obtained for determination of myocardial infarct size as a percentage of area at risk (IS/AAR).Results MAP,HR and RPP were significantly lower at T1-3 than at T0 in each group.Compared with group NS,MAP was significantly increased at T3,and IS/AAR ratio was decreased in MP group,and no significant changes were found in the other groups.Compared with group MP,IS/AAR ratio was significantly increased in L-NAME + MP,ODQ + MP and KT5823 + MP groups,and no significant changes were found in the other groups.Conclusion NO-cGMP-PKG signal transduction pathway plays an important role in mitigation of myocardial ischemia-reperfusion injury by intrathecal morphine postconditioning in rats.