Role of TRPV1/CGRP signaling pathway in lidocaine postconditioning-induced reduction of myocardial ischemia-reperfusion injury in rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of transient receptor potential vanillic acid subtype 1 (TRPV1)/calcitonin gene-related peptide (CGRP) signaling pathway in lidocaine postconditioning-induced reduction of myocardial ischemia-reperfusion (I/R) injury in rats.Methods Forty healthy male SpragueDawley rats,aged 3 months,weighing 250-300 g,were divided into 5 groups (n=8 each) using a random number table method:sham operation group (group Sham),group I/R,lidocaine postconditioning group (group LP),lidocaine postconditioning plus CGRP8-37 group (group LP+CGRP8-37),and lidocaine postconditioning plus capsazepine group (group LP+Capz).Myocardial ischemia was induced by ligating the anterior descending branch of left coronary artery for 30 min,followed by 120-min repeRFusion in anesthetized rats.Lidocaine 2 mg/kg was injected via the tail vein at 5 min before reperfusion in group LP.In group LP + CGRP8-37,lidocaine was intravenously injected,and CGRP receptor selective antagonist CGRP8-37 2 mg/kg was intravenously injected at the same time.In group LP+Capz,lidocaine was injected intravenously,and TRPV1 blocker capsazepine 3 mg/kg was injected intravenously at the same time.A catheter was retrogradely implanted to the left ventricle,and heart rate (HR),left ventricular systolic pressure (LVSP),left ventricular end-diastolic pressure (LVEDP),and the maximum rate of increase or decrease in left ventricular pressure (±dp/dtmax) were continuously monitored and recorded.Blood samples were collected from the carotid artery at 120 min of reperfusion for determination of cardiac troponin I (cTnI),myoglobin (Myo) and creatine kinase-MB (CK-MB) concentrations in serum.Rats were then sacrificed for determination of myocardial infarct size.Results Compared with Sham group,the serum concentrations of cTnI,Myo and CK-MB were significantly increased,LVSP,+dP/dtmax and HR were decreased,and LVEDP and-dP/dtmax were increased in I/R group and LP group (P＜0.05).Compared with group I/R,the serum concentrations of cTnI,Myo and CK-MB and myocardial infarct size were significantly decreased,LVSP and +dP/dtmax were increased,and LVEDP,-dP/dtmax and HR were decreased in group LP (P＜0.05),and no significant change was found in the parameters mentioned above in group LP+ CGRP8-37 and group LP+Capz (P＞0.05).Compared with group LP,the serum concentrations of cTnI and Myo,myocardial infarct size and LVEDP were significantly increased,and + dP/dtmax was decreased in group LP+CGRP8-37,and the serum concentrations of cTnI and Myo and myocardial infarct size were significantly increased,LVSP and +dP/dtmax were decreased,and LVEDP was increased in group I/R+Lido+Capz (P＜0.05).Conclusion The mechanism by which lidocaine postconditioning mitigates myocardial I/R injury is related to activating TRPV1/CGRP signaling pathway in rats.