The effects of naloxone on the post-asphyxic cerebral pathophysiology of newborn lambs.
Both early post-ischaemic blood-brain barrier disruption and enhanced brain endogenous opioid system activity have been implicated in the pathogeneses of ischaemic neuronal damage; however, their roles in neonatal asphyxia have not been evaluated. Under alpha-Chloralose anaesthesia, 17 newborn lambs were asphyxiated until their mean arterial pressures were < or = 25 mmHg. They were then immediately resuscitated, and assigned to two groups. Group I, but not group II lambs received IV bolus of 10 mg kg-1 Naloxone within 5 min of resuscitation. The infusion was continued at the same dose hourly until sacrificed 24 h post-asphyxia. Arterial pH/gases, intracranial/arterial pressures, and rectal temperature were monitored. Neurological examinations were performed on both groups prior to sacrifice, and the blood-brain barrier integrity was assessed by Evans blue. Despite aggressive resuscitation, 5 lambs died during asphyxia, but 12 survived and were assigned according to the protocol. There were no significant group differences in the magnitude of asphyxia, arterial and intracranial pressures. However, blood-brain barrier disruption was observed in 5 out of 6 untreated, and in only 1 of the 6 lambs treated with Naloxone (p < 0.05). Severe neurological abnormalities were observed in 75% of lambs with disrupted, but in none of the animals with intact blood-brain barrier (p < 0.05). Our study suggests that post-asphyxia blood-brain barrier disruption is causally related to poor neurological outcome, and that Naloxone prevents both the disruption, and the neurological dysfunction among those survivors with intact blood-brain barrier.
Ting
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Department of Pediatrics and Child Health, College of Medicine, Howard University, Washington, DC 20059.
Pan
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D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D007231:Infant, Newborn; D007427:Intracranial Pressure / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology*; D009460:Neurologic Examination; D012016:Reference Values; D012151:Resuscitation; D012756:Sheep
D009270:Naloxone