Stroke, Vol 23, 380-387, Copyright © 1992 by American Heart Association
AR Laptook, RJ Corbett, J Ruley and E Olivares
BACKGROUND AND PURPOSE: Our investigation sought to determine whether
neonatal brain ischemic vascular and metabolic effects were altered by
repeated episodes of ischemia. METHODS: We studied twelve piglets using in
vivo magnetic resonance spectroscopy to obtain multiple, simultaneous
measurements of cerebral blood flow and phosphorylated metabolites from the
same tissue volume. The relationship between cerebral blood flow and energy
metabolism was examined over a range of reduced cerebral blood flow (90-10%
of control). Three episodes of partial ischemia were studied, each lasting
10 minutes and separated by 45 minutes. RESULTS: During each interval of
ischemia, plots of the percent reduction in cerebral blood flow versus the
percent change in phosphorylated metabolites (phosphocreatine, inorganic
phosphorus) or unit change in intracellular pH did not differ in slope and
intercept. The relationship between beta-ATP and cerebral blood flow during
repeated ischemia revealed similar slopes, but a lower intercept during the
third interval of ischemia (p = 0.029). After ischemia, cerebral blood flow
was reduced as a function of the severity of the preceding ischemia. After
each interval of ischemia, phosphocreatine and intracellular pH were
unchanged from preischemic values. Inorganic phosphorus remained elevated
after ischemia (117 +/- 16 and 118 +/- 11% of control, p less than 0.005,
following the first and second intervals of ischemia), and beta-ATP was
restored to progressively lower values (92 +/- 10 and 83 +/- 11% of
control, p less than 0.025). Calculated free ADP decreased after ischemia
and correlated with the postischemic level of beta-ATP (r = 0.63, p =
0.001). CONCLUSIONS: These results demonstrate that the relationship
between cerebral blood flow and metabolism was reasonably preserved during
repeated partial ischemia. However, following ischemia, alterations
occurred in both cerebral blood flow and metabolism. These alterations may
reflect a relative inhibition of ATP production by metabolic regulators
such as ADP on either glycolysis or oxidative phosphorylation or both.
ARTICLES
Blood flow and metabolism during and after repeated partial brain ischemia in neonatal piglets
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063.
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