Morphine reduces the threshold of remote ischemic preconditioning against myocardial ischemia and reperfusion injury in rats: the role of opioid receptors.

OBJECTIVES Opioid receptors mediate the cardioprotection of remote ischemic preconditioning (RIPC). The authors tested the hypothesis that morphine reduces the threshold of cardioprotection produced by RIPC. METHODS A randomized, prospective study. SETTING A university research laboratory. PARTICIPANTS Forty-five male Sprague-Dawley rats. INTERVENTIONS Anesthetized, open-chest, male Sprague-Dawley rats were assigned randomly to 1 of 7 treatment groups. RIPC1 and RIPC3 were, respectively, induced by 1 or 3 cycles of 5 minutes of femoral artery ischemia interspersed with 5 minutes of reperfusion. Morphine (MOR, 0.1 mg/kg) and the opioid receptor antagonist naloxone (NAL, 6 mg/kg) were administered 30 minutes before sustaining ischemia. MOR + RIPC1 and NAL + MOR + RIPC1 groups received the combination of MOR and RIPC1 in the absence or presence of NAL before coronary artery occlusion. Ischemia and reperfusion injury then were induced by 30 minutes of left coronary artery occlusion followed by 120 minutes of reperfusion. MEASUREMENTS AND MAIN RESULTS Infarct size, as a percentage of the area at risk, was determined by 2,3,5-triphenyltetrazolium staining. RIPC3 and the combination of MOR and RIPC1 groups significantly reduced the infarct size compared with the control group. RIPC1, MOR, and NAL did not affect infarct size. NAL pretreatment reversed cardioprotection of the combination of MOR and RIPC1 treatments. CONCLUSIONS MOR reduces the threshold of RIPC, and opioid receptors mediate this augmentative effect.