Protective effects of intrathecally remote morphine preconditioning against myocardial ischemia-reperfusion injury in rats / 中华急诊医学杂志

ABSTRACT

Objective To investigate the mechanism of the protective effects induced by intrathecally remote morphine preconditioning (RMPC) against myocardial ischemia-reperfusion (I/R) injury in rats.Method Male SD rats weighing 280 ～ 320 g were used in this study. A needle was inserted through a surgically created hole into the spinal cord space. Sixty male SD rats, in which intrathecal needle was successfully placed without complication, were randomly (random number) divided into 10 groups of 6 animals each. In group Ⅰ myocardial I/R was produced (I/R). In group Ⅱ morphine was given intrathecally in 3 repeated doses of 1 μg/kg at 5 mtn intervals before ischemia (RMPC). Antagonists CGRP8-37 (CGRP receptor antagonist), 8-SPT (adenosine receptor antagonist), HOE-140 (bradykinin B2 receptor antagonist) and HEX (autonomic nerve antagonist) were given intrathecally in group Ⅲ , Ⅳ, Ⅴ and Ⅳrespectively at 10 min before RMPC. In group Ⅶ, Ⅷ, Ⅸ and X CGRP8-37, 8-SPT, HOE-140 and HEX were given intrathecally respectively at 40 min before ischemia. Myocardial I/R was produced by occlusion of left anterior descending branch (LAD) of coronary artery for 30 min followed by 120 min reperfusion. At the baseline and the end of 120 min reperfusion venous blood samples were taken for determination of LDH activity. The animals were then killed and hearts removed for measurement of area at risk (AAR) and infarct size area (IS). IS/AAR was calculated. Results The size of infarct area was smaller and IS/AAR ratio lower and significantly less LDH was released at the time of 120 min reperfusion in RMPC group (group Ⅱ) than in group I/R (group Ⅰ). The protective effects of RMPC was abolished by intravenously pretreatment with CGRP8-37, 8-SPT,HOE-140 and HEX. Conclusions CGRP, adenosine, bradykinin and autonomic nerve are involved in the protective effects of intrathecally remote morphine preconditioning against myocardial I/R injury.