Lung oxidant injury in a model of lung storage and extended reperfusion.
Donor lungs for transplantation are susceptible to "preservation" injury during both storage and postimplantation reperfusion. We investigated whether lung dysfunction seen after storage and reperfusion was associated with any biochemical hallmarks of direct cellular oxidant injury to lipid, protein, or DNA. Heart/lung blocks were extracted from adult rats following pulmonary vascular flush. Lungs were either perfused immediately ex vivo for 2 h with deoxygenated venous rat blood or were stored at 10 degrees C for 13 h before perfusion. Stored lungs had increased airway pressure, pulmonary vascular shunt fraction, wet/dry weight ratio, and parenchymal hemorrhage after perfusion but no change in pulmonary artery pressure compared with immediately perfused lungs. Hypothermic storage caused no biochemical changes in lung tissue. Perfusion of fresh or stored lungs resulted in lipid peroxidation and loss of nonprotein reduced sulfhydryls; sulfhydryl loss was threefold higher in lungs stored before perfusion compared with freshly perfused lungs. Reperfusion of stored, not fresh, lungs was associated with DNA damage. No loss of protein sulfhydryls occurred following lung perfusion. We conclude that DNA damage, loss of reduced nonprotein sulfhydryls, and lipid peroxidation during reperfusion of stored lungs may be responsible for physiologic lung dysfunction.
Christie
N A
NA
Medical Research Council Group in Lung Development, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Smith
D E
DE
Decampos
K N
KN
Slutsky
A S
AS
Patterson
G A
GA
Tanswell
A K
AK
D000818:Animals; D004195:Disease Models, Animal; D008168:Lung / Q000378:metabolism / Q000503:physiopathology*; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism; D016040:Lung Transplantation / Q000502:physiology; D008297:Male; D009926:Organ Preservation / Q000379:methods; D016877:Oxidants / Q000633:toxicity*; D010477:Perfusion / Q000295:instrumentation / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*; D013997:Time Factors
D016877:Oxidants