Postasphyxial cerebral survival in newborn sheep after treatment with oxygen free radical scavengers and a calcium antagonist.
Acute, severe intrapartum asphyxia was mimicked by tying the umbilical cord in the exteriorized fetal sheep. After a standard time period cardiopulmonary resuscitation was instituted. In the treatment group (n = 14) the lambs were given a composition of scavengers of oxygen-derived free radicals and a calcium channel blocker. The control group of lambs (n = 12) was given placebo. The trial was blind and randomized. Hemodynamic and neurophysiological variables were measured from 30 min before asphyxia to 2 h postresuscitation. Mean arterial blood pressure, sagittal sinus venous pressure, heart rate, and cardiac output did not differ between the two groups although dramatic changes took place during asphyxia and resuscitation. Cerebral blood flow measured by 133-Xe washout method increased in both groups immediately after resuscitation. The treated animals retained an augmented cerebral blood flow during the 2 h postresuscitation while the control animals lost the increase of cerebral blood flow. The treated lambs recovered their somatosensory evoked potentials partially or completely in eight of 14 cases while the same figures for the control lambs were one of 12 cases. Immediately after resuscitation the cerebral reactions recovered to some extent in both groups but during the following 2 h the cerebral cortical function deteriorated in the control group but improved in the treated lambs. It is concluded that part of the brain damage in connection with acute, severe asphyxia may be inflicted by oxygen-derived free radicals released during the reoxygenation phase after resuscitation and that oxygen-derived free radical scavengers and calcium channel blockers may find a place in cardiopulmonary resuscitation.
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001238:Asphyxia Neonatorum / Q000150:complications*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D005260:Female; D005609:Free Radicals; D006439:Hemodynamics; D002534:Hypoxia, Brain / Q000209:etiology* / Q000517:prevention & control; D010100:Oxygen / Q000008:administration & dosage / Q000627:therapeutic use*; D011247:Pregnancy; D012151:Resuscitation; D012756:Sheep; D013997:Time Factors
D002121:Calcium Channel Blockers; D005609:Free Radicals; D010100:Oxygen