Background and Purpose Neurological injury after cerebral air embolism may be due to thromboinflammatory responses at sites of air-injured endothelium. Because heparin inhibits multiple thromboinflammatory processes, we hypothesized that heparin would decrease neurological impairment after cerebral air embolism. Methods To first establish a dose of air that would cause unequivocal neurological injury, anesthetized New Zealand White rabbits received either 0, 50, 100, or 150 mu L/kg of air into the internal carotid artery (n=5 in each group). One hour later, anesthesia was discontinued. Animals were neurologically evaluated at 24 hours with the use of a scale ranging from 0 (normal) to 97 (coma) points. In a subsequent experiment, anesthetized rabbits received either heparin (n=17) or saline (n=15) 5 minutes before air injection (150 mu L/kg). Heparin was given as a 200-IU/kg bolus and followed by a constant infusion of 75 IU . kg(-1). h(-1) for 2 hours. Equal volumes of saline were given to control rabbits. Two hours later, anesthesia was discontinued. Animals were neurologically evaluated 24 hours after air embolism. Results There was a monotonic relationship between dose of air and severity of neurological impairment at 24 hours (P=1.1x10(-7)). Animals receiving 150 mu L/kg of air were unequivocally injured (score, 60+/-16). In the second experiment, heparin animals had significantly less neurological impairment at 24 hours (34+/-14) than saline controls (52+/-8) (P=.0013). Conclusions When given prophylactically, heparin decreases neurological impairment caused by severe cerebral arterial air embolism.