Objective:To determine whether the use of nitric oxide (NO)-releasing polymers coated onto the inner surface of extracorporeal circuits can reduce platelet consumption and activation in the absence of systemic heparinization using a rabbit model of venovenous extracorporeal circulation.Design:Prospective, controlled trialSetting:Research laboratory at an academic medical institution.Subjects:New Zealand White RabbitsInterventions:Anesthetized, tracheotomized, and ventilated New Zealand White rabbits were injected with freshly prepared,111In(oxine)3labeled single donor platelets through the external jugular vein. After baseline measurements, these animals were placed on venovenous extracorporeal circulation through a 1-m control circuit or NO test circuit for 4 hrs at a blood flow rate of 109-118 mL/min via roller pump. Four groups were studied: systemically heparinized control circuits, systemically heparinized NO test circuits, nonheparinized control circuits, and nonheparinized NO test circuits. Platelet counts, fibrinogen levels, and plasma free indium levels were measured hourly. Circuits were rinsed and retained for gamma counting after the 4-hr run or when the circuit clotted. Four animals, one from each group, did not receive radiolabeled platelets so that the circuits could be preserved for scanning electron microscopic examination after the 4-hr study.Measurements and Main Results:Platelet consumption was significantly reduced in both the heparinized and nonheparinized NO test groups when compared with the controls (p< .0001 andp< .0004, respectively). Platelet adhesion to the extracorporeal circuits was significantly reduced in the nonheparinized test circuits when compared with the controls (p< .05). Scanning electron microscopic examination of the circuits revealed that in the absence of heparin and in the presence of a NO-releasing surface, platelets retained their spherical nonactivated shape.Conclusions:The incorporation of NO into the surface of extracorporeal circuits reduces platelet consumption and eliminates the need for systemic heparinization in a rabbit model of extracorporeal circulation.