Beta-adrenergic receptors in ischemic and nonischemic canine myocardium: relation to ventricular fibrillation and effects of pretreatment with propranolol and hexamethonium.
To explore possible roles of the sympathetic nervous system (especially the beta-adrenergic receptor and cAMP system) in the pathogenesis of ventricular fibrillation (VF), the authors examined changes in the number of myocardial beta-adrenergic receptors and the cAMP level in animals showing VF after experimental induction of myocardial ischemia. In animals that developed VF approximately 15 min after coronary ligation, the ischemic myocardium had a significantly larger number of beta-adrenergic receptors (90 +/- 8 fmol/mg protein) and a significantly higher level of cAMP (1.4 +/- 0.17 nmol/g weight) compared with the nonischemic area where the number of beta-receptors was 68 +/- 7 fmol/mg protein and the cAMP level was 0.80 +/- 0.20 nmol/g weight. In animals in which VF was electrically induced 20 min after coronary ligation, no elevation was recorded in the ischemic area in terms of the number of beta-adrenergic receptors (49 +/- 6 fmol/mg protein) and the level of cAMP (0.79 +/- 0.06 nmol/g weight). When animals were pretreated with a beta-blocker or a ganglion blocker, coronary ligation did not result in VF. In the ischemic area of these animals, no significant change was noted in the number of beta-adrenergic receptors (54 +/- 7 fmol/mg protein for animals pretreated with a beta-blocker, 56 +/- 3 fmol/mg protein for animals pretreated with a ganglion blocker). These results suggest that there is a strong correlation between the pathogenesis of VF (observed about 15 min after coronary ligation) and the increase of the number of beta-adrenergic receptors and cAMP levels.
D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D006321:Heart / Q000187:drug effects; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D014693:Ventricular Fibrillation / Q000209:etiology* / Q000378:metabolism
D006584:Hexamethonium Compounds; D011943:Receptors, Adrenergic, beta; D018738:Hexamethonium; D011433:Propranolol; D000242:Cyclic AMP