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Activation of Central Opioid Receptors Induces Cardioprotection Against Ischemia-Reperfusion Injury

Gordon T. C. Wong, FANZCA^*, Jiang Ling Ling, MD^*,, and Michael G. Irwin, MD^*

From the *Department of Anaesthesiology, University of Hong Kong, Hong Kong; and Department of Anaesthesiology, Anhui Medical University, China.

Address correspondence and reprint requests to Dr. Gordon T. C. Wong, FANZCA, Room 424, K Block, Queen Mary Hospital, Pokfulam Rd., Hong Kong. Address e-mail to gordon{at}hkucc.hku.hk.

Abstract

Background: Small doses of intrathecal morphine provide cardioprotection similar to that conferred by IV morphine and ischemic preconditioning (IPC). We investigated the relative role of central versus peripheral opioid receptors in intrathecal morphine preconditioning (ITMPC).

Methods: Forty-eight anesthetized, open-chest, male Sprague-Dawley rats were assigned to 1 of 7 treatment groups (n = 6–7) after successful intrathecal catheter placement. ITMPC was achieved by 3 consecutive 5-min intrathecal infusions of morphine (1.0 µg/kg each). This was repeated in the presence of either IV (IV naloxone methiodide + ITMPC) or intrathecally (intrathecal naloxone methiodide [ITNM] + ITMPC) administered naloxone methiodide. This compound was also given via these same routes in the absence of ITMPC (IV naloxone methiodide + ITNM). Intrathecal normal saline and IPC were used as negative and positive controls, respectively. Myocardial ischemia and reperfusion injury were induced by 30 min of left main coronary artery occlusion followed by 2 h of reperfusion. Myocardial infarct size, as a percentage of the area-at-risk, was determined by 2,3,5-triphenyltetrazolium staining.

Results: The infarct size/area-at-risk were significantly reduced in the IPC (22% ± 3%) and ITMPC (26% ± 5%) groups compared with the control group (48% ± 9%) (P < 0.01). The addition of ITNM reversed the cardioprotective effects of ITMPC (45% ± 4%), whereas IV administration of the drug did not have any effect on ITMPC (28% ± 9%, P < 0.01).

Conclusions: Intrathecally administered morphine can produce cardioprotective effects via the activation of central opioid receptors, without the apparent involvement of peripheral opioid receptors.