Free radical generation and the role of allopurinol as a cardioprotective agent during coronary artery bypass grafting surgery.
OBJECTIVE
To determine the time course of free radical generation and the role of allopurinol as a cardioprotective agent during coronary artery bypass surgery.


METHODS
Patients were chosen on a strict 'first come, first chosen' basis, irrespective of their age and sex.


METHODS
Tertiary referral-based hospital and medical research centre.


METHODS
A total of 36 patients underwent nonurgent coronary artery bypass grafting surgery. Eighteen patients were treated with allopurinol and 18 patients acted as control.


METHODS
Allopurinol 300 mg was administered orally, twice a day for one day preoperatively and a single dose (600 mg) was administered on the morning of the day of the operation.


RESULTS
Lipid peroxidation products were measured by assays for thiobarbituric acid reactive substances, mainly malondialdehyde (MDA). There were no considerable changes in either MDA levels or creatine kinase isoenzyme with muscle and brain subunits (CK-MB) activity during the ischemic period. One minute after release of the cross-clamp the level of MDA was raised significantly (P<0.001). This rise correlated with the severity of ischemia in the group treated with allopurinol as well as the control group (r=0.58, P<0.05 and r=0.49, P<0.05, respectively). The level of MDA and the activity of CK-MB were significantly lower in patients treated with allopurinol (P<0.05 and P<0.001, respectively). The increase in CK-MB activity during reperfusion correlated with aortic cross-clamp time in both the groups (r=0.62, P<0.05 and r=0.69, P<0.05, respectively). Preliminary studies using electron spin resonance spin trapping technique also demonstrated a rise in free radical adducts during reperfusion and this corroborated well with the spectrophotometric method.


CONCLUSIONS
The results of this study show that, during bypass surgery, there is an increase in lipid peroxidation products and cardiac creatine kinase enzyme at the onset of reperfusion indicating increased free radical activity. It also suggests that pretreatment with allopurinol could effectively attenuate post-ischemic reperfusion injury.
Movahed
A
A
PD Hinduja National Hospital & Medical Research Center, Bombay, India.
Nair
K G
KG
Ashavaid
T F
TF
Kumar
P
P
D000493:Allopurinol / Q000627:therapeutic use*; D000963:Antimetabolites / Q000627:therapeutic use*; D001026:Coronary Artery Bypass; D003402:Creatine Kinase / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D000963:Antimetabolites; D005609:Free Radicals; D007527:Isoenzymes; D000493:Allopurinol; D003402:Creatine Kinase