EFFECT OF PROPENTOFFYLINE (PPF) ON FREE RADICAL GENERATION DURING HYPOXIA IN NEWBORN PIGLETS. ▴ 2253

Previous studies suggest that adenosine inhibits presynaptic release of excitatory amino acids (EAA) and may reduce free radical generation under hypoxia-ischemia. The present study tests the hypothesis that PPF, an adenosine reuptake inhibitor, will reduce free radical generation during hypoxia. Five normoxic animals (Nx) were compared to 5 hypoxic (Hy) and 5 PPF-treated (10 mg/Kg) hypoxic animals (HyPPF). Hypoxia was induced by decreasing FiO₂ to 10-12% for 60 min to achieve a PaO₂ 15-20 mmHg. Electron spin resonance spectroscopy (ESR) were performed to assess free radical generation. Cerebral cortex was homogenized inα-phenyl-N-tert-butylnitrone (PBN) solution and spin adducts were extracted in toluene for ESR measurements. Signal height of spin adduct spectrum, corresponding to alkoxyl radical, divided by tissue weight, is expressed as mm/g dry tissue. Phosphocreatine (PCr), high energy phosphate, was measured biochemically to determine cerebral energy metabolism. Free radical generation in Nx, Hy and HyPPF was 8.2 ± 2.6, 18.7 ± 5.3 and 11.2 ± 2.6, respectively. PCr level in Nx, Hy and HyPPF was 3.41± 1.26, 0.90 ± 0.42 and 2.20 ± 0.58 μmoles/g, respectively. The data show that free radical generation in Hy was greater than in Nx (p<0.01). PCr concentration was lower in Hy than in Nx(p<0.01). We conclude that administration of PPF decreases free radical generation (p<0.05) and preserves PCr (p<0.01) during hypoxia. We speculate that administration of PPF improve cerebral blood flow by increasing extracellular adenosine concentrations thus maintaining normal tissue oxygenation and preserve high energy phosphates. Furthermore, administration of PPF may decrease EAA concentration and decrease free radical generation by inhibiting EAA-mediated calcium influx. (Funded by NIH-HD-2033, MOD#6-FY94-0135, UCPR 506-93).