Arrhythmogenic potential of dopexamine hydrochloride during halothane anaesthesia in dogs.
Dopexamine hydrochloride (Dopacard) is the novel synthetic catecholamine designed for use in the acute management of a low cardiac output status. In addition to dopaminergic receptor stimulation, dopexamine hydrochloride is a potent beta 2 adrenoceptor agonist with negligible direct beta 1 and no alpha adrenergic effect. The objective of this study was to compare the arrhythmogenic effects of dopexamine hydrochloride and dopamine in dogs anaesthetized with halothane (1.2 MAC). The starting dose for dopexamine hydrochloride was 3.5 micrograms.kg-1.min-1 and for dopamine was 5 micrograms.kg-1.min-1. Concentrations of the drugs were increased until four or more premature ventricular contractions within 15 seconds were produced. All dogs developed ventricular tachycardia when dopamine was administered in concentrations ranging between 18-20 micrograms.kg-1.min-1. Unlike dopamine, dopexamine hydrochloride even at concentrations as high as 50 micrograms.kg-1.min-1 did not induce any atrial or ventricular ectopic beats. Lack of beta 1 and alpha adrenergic agonist effects is a likely explanation for low arrhythmogenicity of dopexamine hydrochloride. Both drugs increase cardiac output; dopexamine hydrochloride primarily by a dose-related increase in heart rate and increased afterload. At the maximal concentration dopexamine hydrochloride increased heart rate from 114 to 150 beat.min-1, mean arterial pressure decreased from 81 mmHg to 45 mmHg and SVR decreased from 2418 to 962 dyne.sec-1cm-5. Myocardial contractility increased only moderately, as evaluated by dP/dt, which increased from 1290 to 1696 mmHg.sec-1. Dopamine had a more marked inotropic effect: the dP/dt increased, at the maximal concentration, from 1480 to 2570 mmHg.sec-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Neustein
S M
SM
Department of Anesthesiology, Mount Sinai School of Medicine, of the City University of New York, NY.
Dimich
I
I
Sampson
I
I
Sadeghi
A
A
Mezrow
C
C
Shiang
H
H
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000769:Anesthesia, Inhalation; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D004298:Dopamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006221:Halothane / Q000008:administration & dosage*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017180:Tachycardia, Ventricular / Q000139:chemically induced; D014655:Vascular Resistance / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D015259:Dopamine Agents; C046318:dopexamine; D006221:Halothane; D004298:Dopamine