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1 Department of Surgery, University of Minnesota, Minneapolis, MN, USA; Biomedical Engineering Institute, University of Minnesota, Minneapolis, MN, USA
2 Department of Surgery, University of Minnesota, Minneapolis, MN, USA; Department of Physiology, University of Minnesota, Minneapolis, MN, USA
3 Department of Surgery, University of Minnesota, Minneapolis, MN, USA; Department of Physiology, University of Minnesota, Minneapolis, MN, USA; Biomedical Engineering Institute, University of Minnesota, Minneapolis, MN, USA
* To whom correspondence should be addressed. E-mail: iaizz001{at}umn.edu.
Pharmacological preconditioning with kappa-opioid receptor agonists is pro-arrhythmic and exerts anti-preconditioning effects in rats. Currently, in swine, it is unknown whether kappa 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) nor-Binaltorphimine (nor-BNI); 6) DADLE+nor-BNI; 7) morphine+nor-BNI; or 8) pentazocine+nor-BNI prior to occlusion (45 minutes) and reperfusion (180 minutes) 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 kappa receptor blockade (nor-BNI). DADLE preconditioning significantly increased ischemia-induced arrhythmias relative to controls, while pentazocine preconditioned animals (n=2) experienced intractable ventricular fibrillation during ischemia. Kappa receptor blockade with DADLE or pentazocine preconditioning alleviated pro-arrhythmic effects. These results suggest that kappa receptor activation during pharmacological preconditioning is pro-arrhythmic in swine.
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