Donor treatment with the lazeroid U74389G reduces ischemia-reperfusion injury in a rat lung transplant model.
BACKGROUND
Antioxidant treatment with lazeroids has proven beneficial for the amelioration of reperfusion injury in experimental lung transplantation. This study compares the effect of donor versus recipient treatment on immediate postoperative graft function.


METHODS
A model of acute double-lung transplantation in rats was used to assess graft function. Transplanted controls after 2 (group I) and 16 hours of ischemia (group II) were compared to a recipient (group III; 16-hour ischemia) and a donor treatment group (group IV; 16-hour ischemia) using the lazeroid U74389G (6 mg/kg). Serial assessment of alveolar-arterial oxygen difference, dynamic lung compliance, airway and pulmonary vascular resistance was obtained during a 2-hour reperfusion period. Final analysis included survival, weight gain, and histologic examination.


RESULTS
Graft function was significantly better after 2 hours of ischemia than in any of the three 16-hour ischemia groups (II, III, IV). After 16 hours of ischemia, donor treatment provided superior graft function with respect to dynamic lung compliance, airway resistance, and alveolar-arterial oxygen difference when compared with groups II and III. The pulmonary vascular resistance was significantly higher in group III when compared with groups II and IV. Graft weight increase reflecting edema was highest in groups III (104%) and II (98%).


CONCLUSIONS
After prolonged ischemia only donor treatment with the lazeroid U74389G was able to significantly reduce ischemia-reperfusion-related graft dysfunction.
Hausen
B
B
Division of Thoracic and Cardiovascular Surgery, Hannover Medical School, Germany.
Mueller
P
P
Bahra
M
M
Ramsamooj
R
R
Morris
R E
RE
Hewitt
C W
CW
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004487:Edema / Q000473:pathology; D007511:Ischemia; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008170:Lung Compliance / Q000187:drug effects; D016040:Lung Transplantation / Q000473:pathology / Q000502:physiology*; D008297:Male; D009926:Organ Preservation; D009929:Organ Size; D010100:Oxygen / Q000097:blood; D011281:Pregnatrienes / Q000627:therapeutic use*; D011650:Pulmonary Alveoli / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D015424:Reperfusion; D015427:Reperfusion Injury / Q000517:prevention & control*; D015996:Survival Rate; D014019:Tissue Donors; D014655:Vascular Resistance / Q000187:drug effects; D015430:Weight Gain
D000975:Antioxidants; D011281:Pregnatrienes; C074965:U 74389F; D010100:Oxygen