Role of xanthine oxidase inhibition in survival from hemorrhagic shock

The irreversible loss of adenine nucleotides and the formation of free radicals have both been suggested as causes of irreversibility following prolonged hemorrhagic shock. This study was performed to assess the effect of xanthine oxidase inhibition (allopurinol 50 mg/kg/day), free radical scavenging (superoxide dismutase 15,000 u/kg, catalase 15,000 u/kg, dimethylsulfoxide 20 mg/kg, and alpha tocopherol 100 mg/kg/day) or both, on the 24-hr survival of dogs subjected to irreversible haemorrhagic shock. Twenty anesthetized dogs were bled to a mean arterial pressure of 30 mm Hg for 4 hr. The dogs were allocated to a control, an allopurinol pretreated, a free radical scavenger, or a combined treatment group. Both groups pretreated with allopurinol had significantly improved survival (P < 0.05) over that seen in the control group, but the free radical scavenger treated group was not significantly different from the control group. This study demonstrates the beneficial effect of xanthine oxidase inhibition on survival, and suggests that it may be due to preservation of adenine nucleotides rather than prevention of free radical formation.