Merit of Anisodamine Combined with Opioidδ-Receptor Activation in the Protection against Myocardial Injury during Cardiopulmonary Bypass

Xuan Hong,Rong Lu,Zhongmin Liu,Huimin Fan,Paul Chan

doi:10.1155/2013/212801

Xuan Hong, Rong Lu + Show 3 more

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https://doi.org/10.1155/2013/212801

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Abstract

Myocardial ischemia/reperfusion (MIR) injury easily occurrs during cardiopulmonary bypass surgery in elderly patients. In an attempt to develop an effective strategy, we employed a pig model of MIR injury to investigate the maximum rate of change of left ventricular pressure, left ventricular enddiastolic pressure, and left intraventricular pressure. Coronary sinus cardiac troponin T (TnT) and adenosine-triphosphate (ATP) content in myocardium were measured. The ultrastructures for MIR injury were visualized by transmission electron microscopy (TEM). The role of δ-opioid receptor activation using D-Ala2, D-Leu5-enkephalin (DADLE) in both early (D1) and late (D2) phases of cardioprotection was identified. Also, the merit of cardioprotection by DADLE in combination with anisodamine, the muscarinic receptor antagonist (D+M), was evaluated. Glibenclamide was employed at the dose sufficient to block ATP-sensitive potassium channels. Significant higher cardiac indicators, reduced TnT and increased ATP contents, were observed in D1, D2, and D+M groups compared with the control group. DADLE induced protection was better in later phase of ischemia that was attenuated by glibenclamide. DADLE after the ischemia showed no benefit, but combined treatment with anisodamine showed a marked postischemic cardioprotection. Thus, anisodamine is helpful in combination with DADLE for postischemic cardioprotection.

Highlights

Myocardial ischemia/reperfusion (MIR) injury is a major determinant of therapeutic outcome during cardiac surgery with cardiopulmonary bypass or before and after cardiac interventional therapy
Using combined therapy with anisodamine, a naturally occurring atropine-like compound that has been characterized in China [17,18,19], we explored the early and late phases of preconditioning with DADLE, the opioid δ-receptor agonist, in an attempt to provide theoretical and experimental evidence for further clinical application in cardioprotection
Statistical significance of higher left ventricular systolic pressure (LVSP) values was observed in groups D1 and D2, compared with that in Group C after cardiopulmonary bypass, 1 h after termination of cardiopulmonary bypass (P < 0.05), and 2 h after termination of cardiopulmonary bypass (P < 0.01)

Summary

Introduction

Myocardial ischemia/reperfusion (MIR) injury is a major determinant of therapeutic outcome during cardiac surgery with cardiopulmonary bypass or before and after cardiac interventional therapy. It is still significant to develop the effective treatment for MIR. It is recognized that ischemic preconditioning (IPC) mitigates MIR injury [1]. Endogenous mediators including opiates, adenosine, and bradykinin are considered to promote the acute IPC which can protect against myocardial stunning and ischemia-induced myocardial injury. The early-phase of protection develops within minutes of the initial IPC and lasts 1 to 2 hours, while the late phase becomes apparent 24 h later and lasts 3 to 4 days. Because of its sustained duration (30–90 min) and the limitation of traditional surgical IPC in clinical application (i.e., clamping the aorta many times before blocking), the protective effect of preconditioning induced by opioid δ-receptor agonist(s) has been indicated [3]

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