title: Anesthetic induction with ketamine inhibits platelet activation before, during, and after cardiopulmonary bypass in baboons.
abstract: The objective of this study was to investigate the effects of antifactor D monoclonal antibody (Mab) 166-32 on platelet activation during and after hypothermic cardiopulmonary bypass (CPB) in baboons. Fourteen baboons (mean weight, 15 kg) underwent hypothermic CPB. Seven of them were treated with a single injection of antifactor D Mab 166-32 (5 mg/kg) and the other seven animals were given saline as control. Each baboon was sedated with an intramuscular injection of 10 mg/kg of ketamine hydrochloride. A 20-gauge angiocatheter was placed in the cephalic vein, and 5 mg of diazepam was administered intravenously. Anesthesia was maintained with 0.80% to 2.25% isoflurane, 100% O2, and an inspiratory tidal volume of 13 mL/kg at a rate of 13 breaths per minute throughout the surgical procedure except during CPB. Pancuronium bromide, 0.1 mg/kg, was administered to achieve adequate muscle paralysis. Blood samples were collected before CPB, during CPB, and 1, 2, 3, and 6 h after CPB. Assays were performed to measure platelet activation [CD62P (P-selectin)] using immunofluorocytometric methods. There were no significant differences on CD62P expression of platelets between control and antibody groups before CPB (105 +/- 12% vs. 99 +/- 8%, P=NS), during normothermic CPB (62 +/- 6% vs. 63 +/- 19%, P=NS), during hypothermic CPB (55 +/- 8% vs. 54 +/- 13%, P=NS), and 1, 3, or 6 h after CPB (74 +/- 20% vs. 81 +/- 11%, P=NS). Anesthetic induction with ketamine caused significant reduction in the platelet activation in both groups. Ketamine did not affect complement, neutrophil, and monocyte activation or cytokine production. Further studies on the mechanisms of platelet inhibition by ketamine are warranted.
authors.affiliation: Congenital Heart Surgery Service, Texas Children's Hospital, Houston, TX, USA. aundar@psu.edu
authors.forename: Akif
authors.initials: A
authors.lastname: Undar
authors.forename: Harald C
authors.initials: HC
authors.lastname: Eichstaedt
authors.forename: Fred J
authors.initials: FJ
authors.lastname: Clubb
authors.forename: Mason
authors.initials: M
authors.lastname: Lu
authors.forename: Joyce E
authors.initials: JE
authors.lastname: Bigley
authors.forename: Blake A
authors.initials: BA
authors.lastname: Deady
authors.forename: Aimee
authors.initials: A
authors.lastname: Porter
authors.forename: William K
authors.initials: WK
authors.lastname: Vaughn
authors.forename: Michael
authors.initials: M
authors.lastname: Fung
mesh_terms: D000704:Analysis of Variance; D000778:Anesthetics, Dissociative / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002315:Cardiopulmonary Bypass; D011416:Complement Factor D / Q000276:immunology; D003975:Diazepam / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology*; D023421:Models, Animal; D010215:Papio; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D000911:Antibodies, Monoclonal; D007649:Ketamine; D011416:Complement Factor D; D003975:Diazepam