Influence of propranolol isomers and atenolol on myocardial cyclic AMP, high energy phosphates and vulnerability to fibrillation after coronary artery ligation in the isolated rat heart.
The isolated rat heart with ligation of the left coronary artery was used to assess the role of the beta 1- adrenergic receptor-cyclic AMP mechanism in the genesis of vulnerability to ventricular fibrillation in early myocardial ischaemia. Coronary artery ligation was followed after 3 min by a reduction in ventricular fibrillation threshold which reached a minimum at 15 min. This was accompanied by reduction of ATP and phosphocreatine while cyclic AMP was significantly increased in ischaemic myocardium. The dl-, l- and d-isomers of propranolol attenuated the decrease in ventricular fibrillation threshold and the increase in ischaemic myocardial cyclic AMP, without altering the tissue depletion of ATP. Specific beta 1-adrenergic receptor antagonism with atenolol did not prevent either the increase of tissue cyclic AMP or the reduction in ventricular fibrillation threshold and high energy phosphates. These findings suggest that the mechanism whereby vulnerability to fibrillation is increased in very early myocardial ischaemia is linked to changes in cyclic AMP content of ischaemic myocardium and appears independent of depletion of myocardial high energy phosphates.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D003327:Coronary Disease / Q000150:complications / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D014693:Ventricular Fibrillation / Q000209:etiology / Q000517:prevention & control*
D010710:Phosphates; D011412:Propanolamines; D010725:Phosphocreatine; D001262:Atenolol; D000255:Adenosine Triphosphate; D011433:Propranolol; D000242:Cyclic AMP