Paper Title
Anti-Arrhythmic Properties of DADLE in Ouabain-Induced Arrhythmia in Rats

Abstract
Opioid receptors open the potassium channels and block the voltage-gated calcium channels and result in membrane hyperpolarization. Hence, they possess negative inotropic effect on the heart function. The cardiac glycoside, ouabain depolarizes the cell membrane that leads to ouabain-induced arrhythmia. The aim of the present experiment was to evaluate the antiarrhythmic properties of the specific delta opioid receptor agonist, D-Ala, D-Leu Enkephalin (DADLE) on ouabain-induced arrhythmia in isolated rat atria. Eighteen male rats including the control and DADLE-incubated (100 nM or 1 μM) ouabain-stimulated groups were used. After induction of anesthesia, the atria were isolated and spontaneously beating rate, chronotropic responsiveness, and onset of arrhythmia and asystole were assessed following incubation by DADLE and stimulation by ouabain using standard organ bath. DADLE significantly postponed the onset of arrhythmia compared to control group (p < 0.01). Although it did not delay the onset of asystole, but was able to significantly increase the heart rate in isolated rat atria (p < 0.01). Moreover, it diminished the positive chronotropic effect of ouabain (p < 0.05). Our results revealed that DADLE could diminish the ouabain-induced arrhythmia in isolated rat atria. The hyperpolarization of cell membrane or reduction of ouabain toxicity might mediate this beneficial effect, which needs for further experiments. Index terms - DADLE, Opioids, Cardiovascular, Arrhythmia, Atria