Changes in cerebral cyclic nucleotides and cerebral blood flow during prolonged asphyxia and recovery in newborn pigs.
Cerebrovascular reactivity is preserved after acute severe asphyxia/reventilation in piglets. We hypothesize that prolonged, partial asphyxia with hypotension causes loss of cerebrovascular reactivity and altered cerebral hemodynamics during recovery. We investigated the changes in cerebrospinal fluid cAMP and cGMP, pial arteriolar diameters and flow, and cerebral blood flow during 1 h of asphyxia and 1 h of recovery. During asphyxia, blood pressure decreased from 10 +/- 0.7 to 4.7 +/- 0.3 kPa and increased during recovery to 6 +/- 0.7 kPa. cAMP increased 3-fold by 20 min of asphyxia, returning to baseline at 40 min of asphyxia. During recovery, cAMP increased 2-fold initially, followed by a decrease to 50% below baseline. cGMP increased after 20 min of asphyxia, with maximum levels observed at 40 min; reventilation resulted in a transient increase in cGMP. Pial arteriolar diameters increased at the onset of asphyxia, then decreased toward baseline; during recovery, a similar pattern occurred. Blood flow to the cerebrum (microspheres) decreased during asphyxia and remained very low during recovery. Pial arteriolar flow but not pial arteriolar diameters followed the changes in cortical cerebral blood flow (i.e. virtually no flow during recovery). During recovery, pial arteriolar reactivity to isoproterenol and histamine decreased significantly. We conclude that 60 min of asphyxic-hypotensive insult results in alterations of cerebral cAMP metabolism which may compromise cellular communications during recovery. Prolonged asphyxia induces "no-reflow" during recovery, even when partial pressures of arterial CO2 and O2 have returned to baseline values, and blood pressure is within the autoregulatory range.
Pourcyrous
M
M
Department of Pediatrics, The University of Tennessee, Memphis 38163, USA.
Parfenova
H
H
Bada
H S
HS
Korones
S B
SB
Leffler
C W
CW
D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000378:metabolism / Q000503:physiopathology*; D001794:Blood Pressure; D001921:Brain / Q000098:blood supply*; D002540:Cerebral Cortex / Q000098:blood supply; D002560:Cerebrovascular Circulation; D000242:Cyclic AMP / Q000134:cerebrospinal fluid*; D006152:Cyclic GMP / Q000134:cerebrospinal fluid*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007231:Infant, Newborn; D008297:Male; D009928:Organ Specificity; D010841:Pia Mater / Q000098:blood supply; D012039:Regional Blood Flow; D013552:Swine; D013997:Time Factors
D000242:Cyclic AMP; D006152:Cyclic GMP