Interaction between spinal opioid and adenosine receptors in remote cardiac preconditioning: effect of intrathecal morphine.
OBJECTIVE
Intrathecal morphine is cardioprotective and also triggers spinal adenosine release. This study investigated the role of spinal and peripheral adenosine receptors in intrathecal morphine cardioprotection.


METHODS
A randomized, prospective study.


METHODS
A university research laboratory.


METHODS
Seventy-two male Sprague-Dawley rats.


METHODS
Anesthetized, 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.


RESULTS
Infarct 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.


CONCLUSIONS
Both 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.
Yao
Lu
L
Department of Anaesthesiology, University of Hong Kong, Hong Kong.
Wong
Gordon Tin Chun
GT
Xia
Zhengyuan
Z
Irwin
Michael Garnet
MG
D000818:Animals; D007278:Injections, Spinal; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009020:Morphine / Q000008:administration & dosage* / Q000378:metabolism*; D011446:Prospective Studies; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*
D011957:Receptors, Opioid; D018047:Receptors, Purinergic P1; D009020:Morphine