Effect of 4-Hydroxypyrazolo (3,4-d) Pyrimidine (Allopurinol) on Postirradiation Cerebral Blood Flow: Implications of Free Radical Involvement

Early transient incapacitation (ETI) is the complete cessation of motor performance, occurring transiently and within the first 30 min following exposure to supralethal doses of ionizing irradiation. Studies have reported severe decreases in regional cerebral blood flow (rCBF) in primates at the same postirradiation time after receiving supralethal doses of gamma irradiation. One study demonstrated a dramatic fall of total cerebral blood flow following a single, 25 Gy, Co exposure. Free radical interactions have been implicated in a large number of pathological conditions including irradiation injury, ischemia, microvascular injury, and cell membrane damage. The triphasic cerebral ischemic response seen after irradiation may be even more damaging than complete ischemia since reperfusion may lead to the formation of additional free radicals. A possible mode of pharmacologic intervention may be the introduction of superoxide dismutase or allopurinol since both have been used to attenuate the biochemical and functional damage usually associated with free radical production. This study was designed to determine whether the inhibition of free radical formation via the preirradiation administration of allopurinol would be successful in altering the postirradiation hypotension and reduced rCBF. The hippocampus and the hypothalamus, were selected for the determination of blood flow in this study since a dramatic, postirradiation decrease in blood flow has been reported in these areas. Pub. in Free Radical Biology and Medicine, v4 p279-284 1988.