Specific bradycardic agents, a new therapeutic modality for anesthesiology: hemodynamic effects of UL-FS 49 and propranolol in conscious and isoflurane-anesthetized dogs.
A "specific bradycardic agent" has direct negative chronotropic actions without producing other systemic or coronary hemodynamic alterations. UL-FS 49, a recently synthesized structural analog of verapamil without classical slow channel calcium blocking activity, is proposed as such an agent. The purpose of this investigation was to characterize the hemodynamic and electrocardiographic actions of UL-FS 49 (0.25, 0.50, and 1.0 mg/kg) and compare its effects with those of propranolol (0.25, 0.50, and 1.0 mg/kg) in conscious or isoflurane-anesthetized (with and without neuromuscular blockade by pancuronium) chronically instrumented dogs. In six groups, comprising 52 experiments, UL-FS 49 was found to be more efficacious than propranolol in reducing heart rate, although this agent did not block the hemodynamic response to isoproterenol. UL-FS 49 produced 45-50% reductions in heart rate in dogs with isoflurane-induced tachycardia as compared to 15 and 30% reductions following propranolol. Furthermore, few other hemodynamic alterations were produced by UL-FS 49 indicating the remarkable specificity of this drug for reducing heart rate. A "specific bradycardic agent" such as UL-FS 49 may be useful clinically during the perioperative period. Such a drug may be especially advantageous for patients with documented or suspected ischemic heart disease, those who cannot tolerate the side effects of beta adrenergic blockade, as well as patients requiring a greater reduction in heart rate than can be obtained with beta adrenergic receptor antagonists.
Riley
D C
DC
Department of Pharmacology, Medical College of Wisconsin, Milwaukee 53226.
Gross
G J
GJ
Kampine
J P
JP
Warltier
D C
DC
D000769:Anesthesia, Inhalation; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007530:Isoflurane; D008297:Male; D011433:Propranolol / Q000494:pharmacology*
D001552:Benzazepines; D002317:Cardiovascular Agents; D011433:Propranolol; D007530:Isoflurane; C043636:zatebradine