ALLOPURINOL MAY ALTER INTRACEIXULAR CEREBRAL METABOLISM DURING HYPOXIA IN NEWBORN PIGLETS

Abstract

Allopurinol is a xanthine oxidase inhibitor and free radical scavenger potentially protective in hypoxic tissue injury. The present studies compare 5 allopurinol-treated, anesthetized, mechanically ventilated newborn piglets to 5 non-treated piglets during normoxia and after 25 min (HYP 1) and 50 min (HYP 2) of hypoxia by ↓FiO2. The allopurinol group received 5 mg/kg IV 30 min prior to hypoxia. Cerebral cortical O2 delivery and O2 consumption were calculated using microsphere determined blood flows. To assess brain cortical oxygenation, phosphocreatine to inorganic phosphate ratio (PCr/Pi) and intracellular pH (pHi) were determined concurrently by 31-P NMR spectroscopy. Sagittal sinus lactate levels and arterial blood gases were also measured. Brain O2 delivery, O2 consumption, and PCr/Pi were the same for the allopurinol treated and non-treated groups during normoxia, HYP 1, and HYP 2. However, arterial pH was significantly lower in the allopurinol treated vs non-treated piglets during both HYP 1 (7.16±0.06 vs 7.30±0.04) and HYP 2 (6.93±0.14 vs 7.11±0.10) despite comparable PCO2 (36 ± 8 vs 39±8), PO2 (24±2 vs 26±6), and baseline pH (7.40±0.10 vs 7.40±0.03). Similarly, cerebral cortical pHi was lower in the allopurinol treated piglets during hypoxia: HYP 1 (6.77±0.21 vs 6.93±0.39) and HYP 2 (6.43±0.22 vs 6.71±0.39) and the increase in sagittal sinus lactate levels during hypoxia was greater for the allopurinol vs non-treated piglets: HYP 1 (9.5±2.5 vs 5.4±2.5) and HYP 2 (14±3.4 vs 6.71 ± 5.7). The data suggest an alteration in the metabolic response to hypoxia of the allopurinol treated group. If allopurinol interferes with hypoxia-induced cerebral cellular adaptation, accelerating brain tissue lactic acidosis, it may contribute to hypoxic tissue damage despite reducing free radical injury by other mechanisms. (NIH #20337).