Leukocyte depletion ameliorates free radical-mediated lung injury after cardiopulmonary bypass.
Activated leukocytes and oxygen free radicals have been implicated in the pathogenesis of lung injury associated with cardiopulmonary bypass. To determine whether leukocyte depletion could prevent this injury, we used a dog model simulating routine cardiac operations. Mongrel dogs (11 to 17 kg) were subjected to cardiopulmonary bypass with a bubble oxygenator and cooled to 27 degrees C. After aortic crossclamping and cardioplegic arrest for 90 minutes, control animals (n = 5) were rewarmed and weaned from bypass, and their condition was then stabilized for 90 minutes. Leukocyte-depleted animals (n = 5) had a leukocyte filter incorporated in the bypass circuit. During bypass, circulating leukocyte counts decreased by 60% in control dogs, and by 97% in leukocyte-depleted animals. Free radical generation (estimated by spectrophotometric assay of plasma conjugated dienes) was significantly reduced by leukocyte depletion during and after bypass. Total hemolytic complement activity and the titer of C5 decreased markedly immediately after the onset of bypass in both the control and leukocyte-depleted animals. Pulmonary function after bypass was better preserved in leukocyte-depleted animals. These data suggest that depletion of circulating leukocytes contributes to lung injury during cardiopulmonary bypass and is associated with increased oxygen radical activity, pulmonary edema, and vasoconstriction. Leukocyte depletion substantially reduced the pulmonary injury seen after cardiopulmonary bypass.
Bando
K
K
Division of Cardiac Surgery, Johns Hopkins Medical Institutions, Baltimore, Md.
Pillai
R
R
Cameron
D E
DE
Brawn
J D
JD
Winkelstein
J A
JA
Hutchins
G M
GM
Reitz
B A
BA
Baumgartner
W A
WA
D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D015941:Complement Hemolytic Activity Assay; D004285:Dogs; D005112:Extracorporeal Circulation; D005609:Free Radicals; D006440:Hemofiltration; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology*; D008168:Lung / Q000473:pathology* / Q000503:physiopathology; D009504:Neutrophils
D005609:Free Radicals