Vol. 284, Issue 6, H2091-H2099, June 2003
Role of 
-opioid receptor activation in pharmacological
preconditioning of swine
James A.
Coles Jr.1,3,
Daniel C.
Sigg1,2, and
Paul A.
Iaizzo1,2,3
Departments of 1 Surgery and
2 Physiology and 3 Biomedical
Engineering Institute, University of Minnesota, Minneapolis,
Minnesota 55455
Pharmacological
preconditioning with 
-opioid receptor agonists is
proarrhythmic and exerts antipreconditioning effects in rats. In swine,
it is unknown whether -opioid receptor stimulation plays a role in
pharmacological preconditioning. Swine were preconditioned with
1) saline (controls), 2)
[D-Ala2,D-Leu5]enkephalin
(DADLE), 3) morphine, 4) pentazocine,
5) norbinaltorphimine (nor-BNI), 6) DADLE + nor-BNI, 7) morphine + nor-BNI, or 8)
pentazocine + nor-BNI before occlusion (45 min) and reperfusion
(180 min) of the left anterior descending coronary artery. Infarct size to area at risk (IS), regional (systolic shortening) and global (pressures and flows) myocardial function, and arrhythmia occurrence were assessed. Only DADLE + nor-BNI preconditioning significantly decreased infarct size compared with controls (47 ± 13 vs.
65 ± 5%, P < 0.05); morphine preconditioning
was not cardioprotective with or without -opioid receptor blockade
(nor-BNI). DADLE preconditioning significantly increased
ischemia-induced arrhythmias relative to controls, whereas
pentazocine-preconditioned animals (n = 2) experienced intractable ventricular fibrillation during
ischemia. -Opioid receptor blockade with DADLE or
pentazocine preconditioning alleviated proarrhythmic effects. These
results suggest that -opioid receptor activation during
pharmacological preconditioning is proarrhythmic in swine.
morphine; norbinaltorphimine; pentazocine
