7. A method for monitoring the effectiveness of allopurinol pretreatment in the prevention of
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British
The protective actions of allopurinol in
ischemic/reperfusion injury seem critically determined by the drug pretreatment
regimen and may involve generalized alterations in tissue antioxidant status.
In the present study, 12 male swine to be used as donors and recipients in a
heart-lung transplantation study were treated with allopurinol
given orally at a dose of 50 mg/kg for 4 days prior to surgery. Red cells from allopurinol-treated animals showed a progressive decrease
in susceptibility to in vitro peroxidative challenge.
Although the degree and time-course of protection showed some degree of interanimal variation, maximal effects were obtained in
most animals after 2-3 days. The extent of red cell protection in both donor
and recipient animals correlated significantly with the functional viability of
the transplanted lung, as assessed by tissue water content. It is suggested
that the susceptibility of red cells to in vitro oxidative damage may provide a
useful functional assessment of generalized alterations in antioxidant status
produced by pharmacological interventions.