The role of oxygen free radicals in postasphyxia cerebral hypoperfusion in newborn lambs.
Previous work in a neonatal lamb model has demonstrated abnormalities in cerebral blood flow (CBF) and oxygen consumption (CMRO2) after asphyxia. Immediately after resuscitation, there was a marked increase in CBF and a significant decrease in CMRO2 compared to control. During the late period after asphyxia (30 min to 4 h), both CBF and CMRO2 were significantly depressed. The same postasphyxia model (n = 16) was used to examine the hypothesis that generation of oxygen free radicals during cerebral reperfusion may be involved in the genesis of late postasphyxia hypoperfusion and depressed CMRO2. Before asphyxia, the animals were pretreated with either inactivated (n = 8) or active (n = 8) polyethylene glycol superoxide dismutase, 5000 U/kg, and polyethylene glycol catalase, 100 000 U/kg. CBF (radioactive microspheres) and arterial and venous (superior sagittal sinus) blood gases and O2 contents were measured during control, and at 5 min, 1 h, 2 h, and 4 h postasphyxia (PA). In the active enzyme group, 5 min postasphyxia CBF was significantly increased compared to control: 211.5 +/- 28.0 versus 78.6 +/- 11.4 ml.100 g-1.min-1, +/- SEM, p less than 0.005. At 1 h (82.9 +/- 17.6), 2 h (62.3 +/- 5.5), and 4 h (78.9 +/- 12.2) PA, CBF did not differ significantly from control. More importantly, CMRO2 did not differ from control at any time PA. In the inactive enzyme group, both CBF and CMRO2 were depressed at 1, 2 and 4 h PA. These findings are consistent with a conclusion that damage by oxygen free radicals during postasphyxia cerebral reperfusion is important to the genesis of late PA blood flow and O2 metabolism abnormalities. To the extent that depressions in CBF and CMRO2 result in ongoing brain injury, agents that ameliorate these abnormalities may improve neurologic outcome.
Rosenberg
A A
AA
Department of Pediatrics, University of Colorado School of Medicine, Denver 80262.
Murdaugh
E
E
White
C W
CW
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001238:Asphyxia Neonatorum; D001921:Brain / Q000098:blood supply*; D002374:Catalase; D005609:Free Radicals; D006439:Hemodynamics; D006801:Humans; D007231:Infant, Newborn; D010100:Oxygen / Q000502:physiology*; D010101:Oxygen Consumption; D012756:Sheep; D013482:Superoxide Dismutase
D005609:Free Radicals; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen