A novel catecholamine, arbutamine, for a pharmacological cardiac stress agent.
Arbutamine, developed for use as a cardiac stress agent, was compared with isoproterenol and dobutamine in anesthetized dogs for cardiovascular actions prior to and after beta-adrenergic blockade with propranolol. The efficacy and safety of arbutamine were also evaluated in a canine model of myocardial ischemia obtained by partially occluding the left anterior descending coronary artery. Comparison of hemodynamic variables in normal dogs showed that arbutamine was approximately equipotent to isoproterenol in increasing heart rate and cardiac contractility, and in decreasing total peripheral vascular resistance and mean arterial blood pressure. Arbutamine was 210 times more potent than dobutamine in increasing cardiac contractility by 70%; however, at this dose dobutamine exhibited a negative chronotropic response. Beta-adrenergic blockade with propranolol shifted the agonist's dose-response curves for heart rate and contractility to the right; however, low doses of dobutamine exhibited a negative chronotropic effect and increased the total peripheral vascular resistance. In dogs subjected to partial left anterior descending coronary artery occlusion, arbutamine produced significant ST-segment deflections, beginning at a dose of 0.1 nmol/kg/min. Impairment of segment shortening, reflecting cardiac wall motion abnormality, was evident at a dose of 0.3 nmol/kg/min. Isoproterenol did not cause significant changes in these parameters. These results show that arbutamine is capable of producing graded increments in cardiac contractility and rate before and after beta-adrenergic blockage in normal dogs. In dogs subjected to coronary artery occlusion, it is capable of provoking myocardial ischemia at dose levels devoid of toxicity.
Nagarajan
R
R
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912, USA.
Abou-Mohamed
G
G
Myers
T
T
Caldwell
R W
RW
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002395:Catecholamines / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology*; D004285:Dogs; D005080:Exercise Test; D006207:Half-Life; D006439:Hemodynamics / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology
D002316:Cardiotonic Agents; D002395:Catecholamines; D004280:Dobutamine; C076559:arbutamine; D007545:Isoproterenol