Interaction Between Spinal Opioid and Adenosine Receptors in Remote Cardiac Preconditioning: Effect of Intrathecal Morphine

ObjectivesIntrathecal morphine is cardioprotective and also triggers spinal adenosine release. This study investigated the role of spinal and peripheral adenosine receptors in intrathecal morphine cardioprotection.DesignA randomized, prospective study.SettingA university research laboratory.ParticipantsSeventy-two male Sprague-Dawley rats.InterventionsAnesthetized, open-chest, male Sprague-Dawley rats were assigned to 1 of 10 treatment groups 3 days after intrathecal catheter placement. Intrathecal morphine cardioprotection was induced with 3 μg/kg of morphine. Intrathecal normal saline was used as the control. The adenosine-receptor antagonist 8-(p-sulfophenyl) theophylline (50 μg/kg or 7.5 mg/kg) was given via intrathecal or intravenous routes, respectively, either 10 minutes before or immediately after morphine or saline. Ischemia reperfusion injury then was induced by 30 minutes of left coronary artery occlusion followed by 120 minutes of reperfusion.Measurements and Main ResultsInfarct size, as a percentage of the area at risk, was determined by 2,3,5-triphenyltetrazolium chloride staining. This was reduced significantly in the morphine group (25% ± 5%) compared with the control (58% ± 3%, p < 0.05). The addition of intravenous 8-SPT either before or after morphine significantly attenuated the cardioprotective effect. In comparison, intrathecal administration of 8-(p-sulfophenyl) theophylline before but not after morphine attenuated the cardioprotective effects of intrathecal morphine.ConclusionsBoth central and peripheral adenosine receptors are involved in the signaling of intrathecal morphine preconditioning. Central receptors are important in the initiation of the process, whereas peripheral receptors have a role in ongoing mediation of the protective effect.