15. Correlation
of red cell antioxidant status and heart-lung function in swine pretreated with
allopurinol (a model of heart-lung transplantation).
Qayumi AK, Godin DV, Jamieson WR, Ko KM, Poostizadeh A.
Although the protection against myocardial ischemia-reperfusion injury by allopurinol has previously been attributed to inhibition of
xanthine oxidase, the
demonstration of protective effects in species devoid of detectable myocardial xanthine oxidase activity argues
against this hypothesis. In the present study, the effects of allopurinol pretreatment in a model of heart-lung
transplantation were examined in swine, a species devoid of myocardial xanthine oxidase activity.
Twenty-eight experiments were performed utilizing the heart-lung
transplantation model--seven controls (14 animals, 7 donors and 7 recipients)
with no preoperative pharmacological intervention, and twenty-one in the
experimental group (42 animals, 21 donors and 21 recipients) with donor and
recipient pretreated with allopurinol 50 mg/kg/day
for 3 days. The effect of allopurinol was determined
on day 2 blood samples assessing red cell antioxidant status by measurement of malondialdehyde (MDA) formation in response to in vitro peroxidative challenge. The experimental group was divided
into subgroups--namely, nonresponders (8 pairs of
animals) and responders (13 pairs of animals) based on the range (mean +/- 2
SD) of erythrocyte MDA levels in the control group. Heart-lung transplantation
was performed in the three groups (control [7], nonresponders
[8], and responders [13]) on day 3 following the final dose of allopurinol administration in the experimental group. Based
on postsurgical assessments of cardiac and pulmonary
function integrity, animals showing the greatest red cell antioxidant response
following allopurinol treatment showed significantly
better recovery compared with the control group. In contrast, animals that did
not respond to allopurinol pretreatment showed
results similar to those of the control (i.e., untreated) group. Furthermore,
red cell MDA levels in all the allopurinol-treated
animals were found to correlate positively (P < 0.001) with the extent of
myocardial and lung dysfunction, as indicated by cardiac index and lung water
measurements, respectively. The present study suggests that allopurinol
protection against ischemia-reperfusion injury may involve generalized
alterations in tissue antioxidant status, and that the measurement of
erythrocyte susceptibility to oxidative challenge could provide a useful
approach to optimizing the effectiveness of therapeutic interventions
undertaken prior to surgery in order to minimize the risk of damage resulting
from postischemic tissue reperfusion.