Detrimental effects of cardiopulmonary bypass in cyanotic infants: preventing the reoxygenation injury

Abstract

Background: Recent experimental studies have shown that acute hypoxia followed by abrupt reoxygenation using cardiopulmonary bypass (CPB) results in an unintended injury mediated by oxygen free radicals, which can be modified by initiating CPB at a lower fraction of inspired oxygen (FiO2) or by leukocyte filtration. However, the clinical relevance of these experimental studies has been questioned because chronic hypoxia may allow compensatory changes to occur.

Methods: Seven acyanotic infants had CPB initiated at an FiO2 of 1.0. Of 21 cyanotic infants, 7 (group 1) had CPB initiated at an FiO2 of 1.0, 6 (group 2) at an FiO2 of 0.21, and 8 (group 3) underwent CPB using leukocyte filtration. Biopsy of right atrial tissue was performed before and 10 to 20 minutes after the initiation of CPB. The tissue was incubated in 4-mmol/L t-butylhydroperoxide (a strong oxidant), and the malondialdehyde (MDA) level was measured to determine the antioxidant reserve capacity. The more MDA produced, the greater was the depletion of tissue antioxidants secondary to oxygen free radical formation during reoxygenation.

Results: There was no difference in the prebypass antioxidant reserve capacity between cyanotic and acyanotic hearts (492 +/- 72 versus 439 +/- 44 nmol MDA/g protein). However, after the initiation of CPB without leukocyte filtration, MDA production rose markedly in the cyanotic (groups 1 and 2) as compared with the acyanotic hearts (322% versus 40%; p < 0.05), indicating a depletion of antioxidants. In cyanotic hearts, initiating CPB at an FiO2 of 1.0 (group 1) resulted in increased MDA production (407% versus 227%) as compared with hearts in which CPB was initiated at an FiO2 of 0.21 (group 2), indicating a greater generation of oxygen free radicals in group 1. Conversely, there was only a minimal increase in MDA production in 8 of the 21 infants (group 3) in whom white blood cells were effectively filtered (19% versus 322%; p < 0.05).

Conclusions: First, increased amounts of oxygen free radicals are generated in cyanotic infants with the initiation of CPB. Second, this production is reduced by initiating CPB at an FiO2 of 0.21 or by effectively filtering white blood cells. Third, these changes parallel those seen in the acute experimental model, validating its use for future study.