Oxygen free radical generation in healthy blood donors and cardiac patients: the protective effect of allopurinol.
Cardiopulmonary bypass (CPB) activates the complement system, which leads to granulocyte activation and free radical production. Free radical activity during CPB has been associated with myocardial dysfunction. However, the relationship between cardiac enzymes and granulocytes to lipid peroxidation in cardiac surgery patients is unknown. Moreover, the effect of allopurinol on lipid peroxidation during mechanical trauma has to be explored. Thirty-four patients undergoing coronary bypass surgery and 26 healthy blood donors participated in this prospective study where granulocyte counts, cardiac enzymes and malondialdehyde (MDA) were measured and related. Allopurinol was used ex vivo, as scavenger, to explore its effect on lipid peroxidation. In the patient group, the mean preoperative MDA level (2.2 +/- 0.7, nmol/ml) significantly increased after 30 min of bypass (3.3 +/- 0.9 nmol/ml; p < 0.0001), and showed a second peak at aortic declamping (4.1 +/- 0.9 nmol/ml). There were significant correlations between MDA and granulocyte counts (r = 0.59, p < 0.0001) and cardiac enzymes (r = 0.55, p < 0.0001). In an ex vivo setting, further mechanical trauma to blood significantly increased the MDA levels, both in the control (p < 0.0001) and in the patient group (p < 0.0001) and this effect could be reduced by allopurinol (p < 0.0001). CPB and mechanical trauma generate oxygen free radicals. Allopurinol was found to reduce lipid peroxidation of red cells following mechanical trauma and this has to be further investigated regarding its ability to reduce morbidity in patients undergoing open heart surgery.
Belboul
A
A
Department of Thoracic and Cardiovascular Surgery, Sahlgrenska University Hospital, Göteborg, Sweden.
Roberts
D
D
Börjesson
R
R
Johnsson
J
J
D000328:Adult; D000368:Aged; D000493:Allopurinol / Q000494:pharmacology / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers; D001782:Blood Donors; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003167:Complement Activation / Q000187:drug effects*; D003250:Constriction; D003402:Creatine Kinase / Q000097:blood; D052279:Creatine Kinase, MB Form; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D005609:Free Radicals; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019271:Hypoxanthine / Q000494:pharmacology; D007527:Isoenzymes / Q000097:blood; D007958:Leukocyte Count; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood*; D008875:Middle Aged; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects; D013314:Stress, Mechanical; D013482:Superoxide Dismutase / Q000502:physiology; D014969:Xanthine Oxidase / Q000494:pharmacology
D015415:Biomarkers; D016166:Free Radical Scavengers; D005609:Free Radicals; D007527:Isoenzymes; D017382:Reactive Oxygen Species; D019271:Hypoxanthine; D008315:Malondialdehyde; D000493:Allopurinol; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form