TY - JOUR
T1 - Role of κ-opioid receptor activation in pharmacological preconditioning of swine
AU - Coles, James A.
AU - Sigg, Daniel C.
AU - Iaizzo, Paul A.
PY - 2003/6/1
Y1 - 2003/6/1
N2 - Pharmacological preconditioning with κ-opioid receptor agonists is proarrhythmic and exerts antipreconditioning effects in rats. In swine, it is unknown whether κ-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 κ-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. κ-Opioid receptor blockade with DADLE or pentazocine preconditioning alleviated proarrhythmic effects. These results suggest that κ-opioid receptor activation during pharmacological preconditioning is proarrhythmic in swine.
AB - Pharmacological preconditioning with κ-opioid receptor agonists is proarrhythmic and exerts antipreconditioning effects in rats. In swine, it is unknown whether κ-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 κ-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. κ-Opioid receptor blockade with DADLE or pentazocine preconditioning alleviated proarrhythmic effects. These results suggest that κ-opioid receptor activation during pharmacological preconditioning is proarrhythmic in swine.
KW - Morphine
KW - Norbinaltorphimine
KW - Pentazocine
UR - http://www.scopus.com/inward/record.url?scp=0038781998&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038781998&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00843.2002
DO - 10.1152/ajpheart.00843.2002
M3 - Article
C2 - 12543635
AN - SCOPUS:0038781998
SN - 0363-6135
VL - 284
SP - H2091-H2099
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 6 53-6
ER -