Preliminary administration of dynorphin AH3 tO narcotized cats with myocardial ischemia attenuated cardiac fibrillation, but increased the incidence of ventricular tachycardia. Protective effect of dynorphin A1_13 was observed only under conditions of intact sympathetic cardiac innervation.
Key Words: dynorphin A~.13; to-opiate receptors; myocardial ischemia; cardiac arrhythmia; stellate ganglionRecent studies demonstrated the presence of la-,~5-, and K:-opiate receptors in the heart. Dynorphin AH3 (DYN) is a selective agonist of n-opiate receptors [6]. Agonists of ~t-and ~-opiate receptors posses considerable antiarrhythmic properties in myocardial ischemia [7,12], but the role of~:-opiate receptors and the effects of DYN on heart rhythm received little attention. Experiments on the isolated heart showed that DYN increased the incidence of cardiac arrhythmia and cAMP concentration in the heart, while naloxone completely abolished these effects [11]. Neurogenie mechanisms play an important role in the pathogenesis of ischemic cardiac arrhythmias [3]. Moreover, n-opiate receptors were found in brain regions involved in the regulation of the cardiovascular system and in sympathetic postganglionic fibers innervating coronary vessels and cardiomyocytes [14]. Here we studied the effects of DYN on the development of cardiac arrhythmias and possible sympathetic mechanisms of this action.
MATERIALS AND METHODSExperiments were performed on 49 male and female cats weighing 2-4 kg and narcotized with Nembutal Russian State Medical University, Moscow (40 mg/kg intraperitoneally). Myocardial ischemia was induced by occlusion of circumflex branch of the left coronary artery. The development of arrhythmia was monitored over 15-min myocardial ischemia and 15-min reperfusion. Our previous studies showed that under these conditions, idioventricular rhythm, ventricular tachycardia, and ventricular fibrillation were observed in 72, 28, and 56% observations, respectively [8].Electrocardiogram and blood pressure in the femoral artery and left ventricle were recorded on a Biokomb-8 polyphysiograph (Orion/EMG).The selective ~:-opiate receptor agonist DYN (Laboratory of Peptide Synthesis, Russian Cardiology Research Center) in a dose of 40 pg/kg was intravenously infused for 15 min from the moment of coronary occlusion.In series I (n=12), coronary occlusion (CO) was performed against the background of DYN administration and intact cardiac innervation. In series II (n=10), CO and infusion of DYN was preceded by bilateral vagotomy and transection of cardiac branches of the stellate ganglia (5 min before CO). In series III, cardiac branches of stellate ganglia were transected 5 min before CO in animals with (n=10) or without (n= 10) DYN infusion. In series 4 (n=7), DYN effects on adrenergic properties of the heart were studied by 0007-4888/00/0001-27525.00 9Kluwer Academic/Plenum Publishers