BLOOD-FLOW AND METABOLISM DURING AND AFTER REPEATED PARTIAL BRAIN ISCHEMIA IN NEONATAL PIGLETS

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 < 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 < 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.