title: The role of morphine in a rat model of hypoxic-ischemic injury.
abstract: We investigated whether morphine plays a neuroprotective role in a neonatal rat pup model of bilateral carotid artery occlusion with hypoxia. At postnatal day 10, rats received either morphine (n = 7), naloxone (n = 7), or saline placebo (n = 15) after hypoxic-ischemic injury. Survival (days), weight gain and animal testing (negative geotaxis, surface righting, and rotarod) were compared between treatment groups. Lesion volume was delineated with magnetic resonance imaging at days 7 and 28-57 after injury. Survival in rats treated with morphine, naloxone, or saline was, respectively, 14, 29, and 73%. Median number of days of survival after bilateral carotid artery occlusion with hypoxia treated with morphine was 4 (95% confidence interval 4 to 22), with naloxone was 3 (95% confidence interval -1.4 to 21), and with placebo was 28 (95% confidence interval 18 to 28). There were no statistically significant differences in magnetic resonance imaging-derived ischemic lesion volumes, weight gain, or behavioral testing measures between the groups. Morphine was ineffective as a neuroprotectant in rat pups with severe hypoxic-ischemic injury and may have contributed to their decreased survival.
authors.affiliation: Department of Emergency Medicine, Division of Pediatric Emergency Medicine, Loma Linda University Children's Hospital, Loma Linda, California, USA. afestekjian@chla.usc.edu
authors.forename: Ara
authors.initials: A
authors.lastname: Festekjian
authors.forename: Stephen
authors.initials: S
authors.lastname: Ashwal
authors.forename: Andre
authors.initials: A
authors.lastname: Obenaus
authors.forename: Danilyn M
authors.initials: DM
authors.lastname: Angeles
authors.forename: T Kent
authors.initials: TK
authors.lastname: Denmark
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D020925:Hypoxia-Ischemia, Brain / Q000401:mortality* / Q000473:pathology* / Q000517:prevention & control; D055104:Infusions, Subcutaneous; D008297:Male; D009020:Morphine / Q000008:administration & dosage* / Q000627:therapeutic use; D009270:Naloxone / Q000008:administration & dosage; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate / Q000639:trends
chemical_list: D018696:Neuroprotective Agents; D009270:Naloxone; D009020:Morphine