Dexmedetomidine partially attenuates the sympathetically mediated systemic and coronary hemodynamic effects of cocaine.
The hemodynamic effects of cocaine may be modulated by drugs which interact with central and peripheral adrenoceptors. This investigation examined the systemic and coronary hemodynamic effects of cocaine in conscious dogs with and without premedication with dexmedetomidine (DM). Three groups consisting of 24 experiments were performed using eight dogs chronically instrumented for measurement of aortic and left ventricular pressure, left ventricular dP/dtmax, diastolic coronary blood flow velocity, cardiac output, and subendocardial segment length. On separate experiment days, systemic and coronary hemodynamics were recorded after cocaine (0.5 mg/kg intravenously [I.V.]) with or without DM pretreatment (2 or 4 micrograms/kg I.V.). Cocaine caused increases in heart rate, mean arterial pressure, left ventricular systolic and end-diastolic pressures, dP/dtmax, cardiac output, systemic vascular resistance, and pressure-work index in conscious dogs. Pretreatment with DM attenuated increases in heart rate, dP/dtmax, cardiac output, and pressure-work index produced by cocaine. Systemic vascular resistance increased after the administration of cocaine with and without DM pretreatment; however, systemic vascular resistance remained higher after cocaine in DM-pretreated dogs compared to untreated dogs. Increases in diastolic coronary vascular resistance, but no change in coronary flow velocity, were observed with cocaine alone. In contrast, cocaine increased diastolic coronary blood flow velocity without change in diastolic coronary vascular resistance when administered after DM. The results indicate that increases in heart rate, myocardial contractility, and myocardial oxygen consumption caused by cocaine were attenuated by DM pretreatment. However, cocaine-induced increases in systemic vascular resistance were augmented by DM, suggesting an additive effect at peripheral vascular alpha adrenoceptors.
Kersten
J R
JR
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
Pagel
P S
PS
Hettrick
D A
DA
Warltier
D C
DC
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004285:Dogs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D020926:Medetomidine; D011292:Premedication
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D003042:Cocaine; D020926:Medetomidine