Effects of dopexamine on hemodynamics and oxygen consumption after beta blockade in lambs.
OBJECTIVE
Dopexamine is a synthetic catecholamine with predominantly beta 2 and dopaminergic adrenergic receptor activities. We investigated its effects on systemic and myocardial hemodynamics and oxygen consumption (VO2) in a newborn species and studied its predominant mechanism of action.


METHODS
Prospective dose-response study with each animal serving as it own control.


METHODS
Eight chronically instrumented, unanesthetized lambs, 9 to 11 days of age.


METHODS
After surgical instrumentation and recovery for 72 hrs, animals were infused with dopexamine at increasing doses (1, 10, and 100 micrograms/kg/min) for 5 mins each before and after beta 1 (metoprolol) and beta 1, beta 2 (propranolol) adrenergic receptor blockade. All studies were performed during normoxia.


RESULTS
Heart rate (HR) increased with increasing infusion rates of dopexamine and systemic arterial pressure and vascular resistance decreased. Cardiac index, left ventricular pressure development, and systemic VO2 were unchanged, as was the rate x pressure product. Left circumflex coronary artery blood flow and myocardial VO2 were unaltered. After beta 1-blockade, dopexamine produced an increase in HR and decreased systemic arterial pressure and vascular resistance. After beta 1-adrenergic receptor blockade, no change was noted in systemic or myocardial VO2, coronary blood flow, or rate x pressure product. After beta 1, beta 2-blockade with propranolol, increasing infusion rates of dopexamine resulted in decreases in systemic pressure and vascular resistance.


CONCLUSIONS
Dopexamine produced significant cardiovascular effects mediated primarily by beta 2-adrenergic receptors, and also produced residual peripheral arterial vasodilation after combined beta 1- and beta 2-blockade. The latter finding suggests that dopaminergic receptor stimulation may partly mediate dopexamine's effects in newborn lambs.
Taylor
B J
BJ
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock 72205.
Rogers
B W
BW
Sziszak
T L
TL
Sziszak
T J
TJ
D000818:Animals; D000831:Animals, Newborn; D004298:Dopamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012756:Sheep; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents; C046318:dopexamine; D011433:Propranolol; D007545:Isoproterenol; D004298:Dopamine