Doxycycline Reduces Early Neurologic Impairment after Cerebral Arterial Air Embolism in the Rabbit

Abstract

Background Previous studies indicate leukocytes play a role in the pathogenesis of cerebral arterial air embolism. Because doxycycline inhibits numerous leukocyte activities, the authors hypothesized doxycycline would decrease neurologic impairment after cerebral arterial air embolism. Methods New Zealand White rabbits anesthetized with methohexital received either intravenous saline (n = 7) or 10 mg/kg doxycycline (n = 7) 1 h before administration of 100 microl/kg of air into the internal carotid artery. Somatosensory-evoked potentials (SSEPs) were recorded at 30-min intervals for the next 2 h. After the final recording, the anesthetic was discontinued, and animals recovered. Animals were neurologically evaluated 4 h after air embolism on a scale of 0 (normal) to 99 (coma) points. Results At 4 h, doxycycline animals had lesser neurologic impairment (46 +/- 23; median, 41) than animals that received saline (77 +/- 20; median, 81); P = 0.007. SSEP amplitude was greater in the doxycycline group at 60, 90, and 120 min after air embolism; P = 0.001, 0.006, 0.026, respectively. SSEP amplitudes at 30, 60, 90, and 120 min inversely correlated with 4 h neurologic impairment; tau = -0.43, -0.75, -0.85, -0.79, respectively. Conclusions Doxycycline decreased electrophysiologic and neurologic abnormalities after cerebral air embolism. Because groups could be distinguished electrophysiologically as soon as 1 h after air embolism and because SSEP amplitude inversely correlated with neurologic impairment, doxycycline appears to inhibit a key early (approximately 1 h) process in the pathophysiology of cerebral air embolism.