Platelet anesthesia with nitric oxide with or without eptifibatide during cardiopulmonary bypass in baboons.
OBJECTIVE
This study tested the hypothesis that nitric oxide or nitric oxide and eptifibatide (Integrilin) reversibly inhibit platelet activation and consumption during cardiopulmonary bypass and rapidly restore platelet numbers and function after bypass.


METHODS
Nitric oxide, a short-acting, reversible platelet inhibitor, was studied with and without eptifibatide, a short-acting, reversible glycoprotein IIb/IIIa inhibitor, in 21 baboons that underwent 60 minutes of normothermic cardiopulmonary bypass with peripheral cannulas. A control group, a group that received 80 ppm nitric oxide, and a group that received both nitric oxide and eptifibatide were studied. Blood samples were obtained at several time points to determine platelet count, aggregation in response to adenosine diphosphate, and levels of beta-thromboglobulin, prothrombin fragment 1.2, and thrombin-antithrombin complex. Template bleeding times were measured before and at 4 intervals after cardiopulmonary bypass.


RESULTS
Both nitric oxide and the combination of the 2 drugs significantly attenuated platelet consumption, improved postbypass function, and reduced plasma beta-thromboglobulin release with respect to values in control animals. Both nitric oxide and the combination restored baseline bleeding times 55 minutes after cardiopulmonary bypass ended. No significant differences between nitric oxide and the combination were found for any measurement.


CONCLUSIONS
Nitric oxide with or without eptifibatide protects platelets during cardiopulmonary bypass and accelerates restoration of normal bleeding times after operation in a baboon model. Although nitric oxide and eptifibatide reversibly inhibit platelets by different mechanisms, in the absence of a wound no synergistic effect was demonstrated.
Suzuki
Y
Y
Harrison Surgical Research Laboratories, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, USA.
Malekan
R
R
Hanson
C W
CW
Niewiarowski
S
S
Sun
L
L
Rao
A K
AK
Edmunds
L H
LH
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002315:Cardiopulmonary Bypass; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000077542:Eptifibatide; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007432:Intraoperative Period; D009569:Nitric Oxide / Q000494:pharmacology*; D010215:Papio; D010455:Peptides / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010976:Platelet Count / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011183:Postoperative Complications / Q000517:prevention & control; D013927:Thrombosis / Q000097:blood / Q000517:prevention & control
D016166:Free Radical Scavengers; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D009569:Nitric Oxide; D000077542:Eptifibatide