12. Response to allopurinol pretreatment in a swine model of heart-lung
transplantation.
Qayumi AK, Jamieson WR, Godin DV, Lam S, Ko KM, Germann E, Van den Broek J.
Department of Surgery, Faculty of Medicine,
The role of allopurinol in the prevention of
ischemia-reperfusion injury was assessed in a model of heart-lung transplantation.
Fourteen swine were divided into two groups (seven donors and seven
recipients). All heart and lung blocks were placed in hypothermic storage after
perfusion with cold iso-osmolar cardioplegic
solution and modified Collins solution, respectively (t = 8-10 degrees C for
heart and t = 16-18 degrees C for lungs). The total ischemic time including the
orthotopic transplantation was 6 h. Animals (donors
and recipients) were pretreated with allopurinol
given orally at a dosage of 50 mg/kg for 4 days. Animals were assessed by
monitoring heart and lung function, including extravascular
lung water at three time intervals, which included pretransplantation
(donor), and 30 min and 2 h posttransplantation
(recipient). Erythrocyte peroxidation susceptibility
was assessed for 3 days, and surgery was performed on day 4. The malondialdehyde levels determined from erythrocyte exposure
to in vitro peroxidative challenge classified three
paired donor and recipient animals as responders and four paired donor and
recipient animals as nonresponders to the allopurinol pretreatment. A persistent deterioration of
lung function was observed over time in nonresponders
(p less than .05) (increase of lung water, decrease of partial pressure of
oxygen, increase in alveolar-arterial gradient, and decrease in
arterial-alveolar tension ratio). Responders showed no significant alterations
in lung function. This study in swine, a species devoid of myocardial xanthine oxidase activity,
indicates that allopurinol may have a mechanism of
action other than xanthine oxidase
inhibition in the prevention of ischemia-reperfusion injury. The parallelism
between protection of lung function and of red blood cells suggests the
involvement of a generalized increase in tissue antioxidant capacity.