Pulmonary vascular permeability after cardiopulmonary bypass and its relationship to oxidative stress.

Abstract

To assess the relationship between oxidative stress resulting from cardiopulmonary bypass and the onset of increased pulmonary vascular permeability. Prospective, controlled study. Adult intensive care unit of a postgraduate teaching hospital. Ten patients undergoing surgery requiring cardiopulmonary bypass, and seven normal subjects. Cardiopulmonary bypass in ten patients undergoing surgery. Protein accumulation index was measured in patients after surgery and in normal subjects as a marker of increased pulmonary vascular permeability. Plasma markers of lipid peroxidation (lipid peroxides and thiobarbituric acid-reactivity), plasma chelatable iron, total non-heme iron, transferrin, and primary plasma proteinaceous antioxidant activities were measured before and after cardiopulmonary bypass, and compared with those values found in normal subjects. Protein accumulation index was significantly higher (1.79 +/- 0.54 [SEM]) in the postcardiopulmonary bypass patients compared with healthy subjects (0.33 +/- 0.07, p < .05). Concentrations of lipid peroxides precardiopulmonary bypass were similar to those concentrations in control patients (0.020 +/- 0.003 vs. 0.031 +/- 0.002 nmol/mg protein), but were significantly increased postcardiopulmonary bypass (0.114 +/- 0.010 nmol/mg protein, p < .01). Thiobarbituric acid-reactive substances were higher precardiopulmonary bypass than those in controls (0.052 +/- 0.01 vs. 0.019 +/- 0.01), and increased postcardiopulmonary bypass (0.072 +/- 0.012), although they did not reach significance. Bleomycin-chelatable iron, indicative of transient plasma iron-overload, was only found in one patient (6.5 mumol/L) postcardiopulmonary bypass. Total plasma non-heme iron concentrations before cardiopulmonary bypass were similar to those concentrations in normal control patients (0.19 +/- 0.03 vs. 0.22 +/- 0.015 nmol/mg of protein), and significantly increased postcardiopulmonary bypass (0.48 +/- 0.08, p < .01). Transferrin concentrations were lower in cardiopulmonary bypass patients (2.43 +/- 0.17 vs. 2.89 +/- 0.03 g/L) than in controls and significantly decreased postcardiopulmonary bypass (1.55 +/- 0.09 g/L, p < .01). High plasma iron concentrations with a lower level of transferrin, postcardiopulmonary bypass, gave significantly increased mean percentage iron-saturation of transferrin, increasing from 27.1% to 61.7% (p < .01). Proteinaceous primary antioxidant activities, measuring iron-binding and iron-oxidizing protection of peroxidizing lipid membranes, were both significantly decreased postcardiopulmonary bypass (83.7 +/- 3.71% pre and 26.6 +/- 8.42% post, p < .01, and 51.2 +/- 2.96% pre and 29.0 +/- 2.94% post, p < .01, respectively). In 90% of the cardiopulmonary bypass patients, there was a significant correlation between the percent increase in iron saturation of transferrin and the protein accumulation index. Pulmonary vascular permeability was significantly increased in patients postcardiopulmonary bypass compared with normal subjects. This patient population also had significantly increased plasma markers of lipid peroxidation compared with normal subjects. Cardiopulmonary bypass induced further increases in lipid peroxidation products but a substantial decrease in proteinaceous primary antioxidants. In the majority of patients, there was a significant correlation between the iron saturation of transferrin and the protein accumulation index.