Beagle puppy model of perinatal asphyxia: alterations in cerebral blood flow and metabolism.
Perinatal asphyxia remains a major cause of neurodevelopmental handicap. The neuropathologic and clinical sequelae of perinatal asphyxia are likely attributable to alterations in cerebral blood flow (CBF) to the developing brain with uncoupling of CBF and metabolism. The newborn beagle puppy model was used to study the control of CBF in physiologic and pathologic conditions in the developing brain. Pups, 2-10 days of age, were randomized to asphyxial insult (i.e., ventilator lines clamped for 5 min) or no insult. In the first series, pups underwent radioactive microsphere determinations of CBF immediately prior to insult (t = 0), at the end of insult (t = 5), and after 60 min of observation (t = 65). In the second series, utilizing a 2.0 tesla superconducting magnet, pups underwent continuous serial in vivo 31P nuclear magnetic resonance spectral analysis of cerebral hemispheric metabolic state. Animals exposed to insult had significant alterations in PO2, PCO2, pH, and mean arterial pressure at the end of insult compared to control pups (all pups: p less than 0.001). Serial CBF data demonstrated decreases in flow in cortical gray and white matter regions during insult and return to baseline 1 hour later; brainstem structures were hyperemic during insult. Analysis of phosphorylated metabolites inorganic phosphorus (Pi), phosphocreatine (PCr), and ATP demonstrated that during insult both the PCr/Pi and ATP/Pi ratios were depressed but by 20-30 min following insult, these ratios of cerebral phosphorylated metabolites had almost returned to baseline values. These data demonstrate that even after a severe asphyxial episode which results in electrocerebral silence, CBF and metabolism may return to normal.
Ment
L R
LR
Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06510.
Stewart
W B
WB
Gore
J C
JC
Duncan
C C
CC
D000136:Acid-Base Equilibrium; D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000503:physiopathology*; D001794:Blood Pressure; D001921:Brain / Q000503:physiopathology; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D004285:Dogs; D004734:Energy Metabolism; D006801:Humans; D002534:Hypoxia, Brain / Q000503:physiopathology; D007231:Infant, Newborn; D010100:Oxygen / Q000097:blood; D010710:Phosphates / Q000097:blood
D010710:Phosphates; D002245:Carbon Dioxide; D010100:Oxygen