title: The effect of dobutamine on platelet aggregatory function in newborn piglets with hypoxia and reoxygenation.
abstract: Dobutamine, a beta-adrenoceptor agonist that is often used to treat myocardial dysfunction in asphyxiated neonates, may act on the adrenoceptors of platelets resulting in activation. Little information is available on the effect and mechanistic pathway of dobutamine on the platelet aggregatory function in neonatal asphyxia. Newborn piglets were acutely instrumented and exposed to hypoxia for 2 h and reoxygenation for 4 h. Piglets were randomized to receive dobutamine infusion (5, 10, or 20 microg/kg per min) or saline (hypoxic-control) at 2 to 4 h of reoxygenation (n = 8 each), and sham-operated animals were not exposed to hypoxia and reoxygenation (n = 6). Platelet number, collagen-stimulated whole blood aggregation, and plasma concentrations of thromboxane B2 were studied. The effects of alpha- and beta-adrenoceptor antagonists (phentolamine and propranolol, respectively) on platelet aggregation to in vitro administration of dobutamine (3 microM) were also examined. Shock and metabolic acidosis developed similarly in all hypoxia-reoxygenated groups. At 4 h of reoxygenation, platelet numbers in all groups decreased, with no differences among groups. Platelet aggregation deteriorated significantly with a rightward shift of concentration-response curve in piglets receiving 10 and 20 microg/kg per min of dobutamine. The group that received 20 microg/kg per min of dobutamine had increased plasma thromboxane B2 concentrations from baseline (P < 0.05). The platelet aggregatory response induced by 3 microM of dobutamine was improved by the coadministration of the beta-but not the alpha-adrenoceptor antagonist. We observed platelet aggregatory dysfunction in hypoxic-reoxygenated newborn piglets treated with high-dose dobutamine. Further investigation is needed to examine the differential effects of dobutamine and hypoxia-reoxygenation in platelet aggregation in newborns.
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Zakariya
authors.initials: Z
authors.lastname: Al-Salam
authors.forename: Marwan
authors.initials: M
authors.lastname: Emara
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wehlage
authors.forename: Sameh
authors.initials: S
authors.lastname: Abozaid
authors.forename: Scott T
authors.initials: ST
authors.lastname: Johnson
authors.forename: David L
authors.initials: DL
authors.lastname: Bigam
authors.forename: Po-Yin
authors.initials: PY
authors.lastname: Cheung
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001792:Blood Platelets / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004280:Dobutamine / Q000494:pharmacology*; D006339:Heart Rate; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia; D008954:Models, Biological; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects*; D012120:Respiration Disorders / Q000188:drug therapy* / Q000503:physiopathology; D013552:Swine; D013929:Thromboxane B2 / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D004280:Dobutamine; D013929:Thromboxane B2; D003094:Collagen; D010100:Oxygen