Fibrinolytic treatment improves the quality of lungs retrieved from non-heart-beating donors.
BACKGROUND
The use of non-heart-beating donors (NHBDs) is an alternative strategy to increase the limited number of donors. The ex vivo evaluation has been proposed to assess the function of the lungs from NHBDs as an interim evaluation of the graft before transplantation. We evaluated the effect of a fibrinolytic agent, urokinase, in a pig ex vivo evaluation model.


METHODS
Domestic pigs (30-38 kg) were divided in 3 groups of 5 pigs each. In the Control Heart-Beating Donor (HBD) Group, the lungs were flushed, explanted, and stored in cold solution (4 degrees C) of low potassium dextran for 4 hours. The pigs in the other 2 study groups were non-heart-beating donors (NHBD), and their lungs were topically cooled for 1 hour in the closed chest after 3 hours of warm ischemia. Urokinase (100,000 IU) was added into the perfusate during reperfusion 1n 1 of the NHBD groups (NHBD-UROK). Hemodynamic and aerodynamic parameters were measured. The wet-to-dry weight ratio was calculated.


RESULTS
There was a significant difference between NHBD-UROK and NHBD Groups in pulmonary vascular resistance (22.5 +/- 3.06 vs 39.02 +/- 6.6 Wood Units, p = 0.032), partial pressure of arterial oxygen/fraction of inspired oxygen (250.8 +/- 23.3 vs 148.9 +/- 14.6 mm Hg, p = 0.032), oxygenation index (6.9 +/- 0.7 vs 15.9 +/- 3.2, p = 0.016), and wet-to-dry weight ratio (5.99 +/- 0.2 vs 7.74 +/- 0.3, p = 0.016). Pulmonary vascular resistance did not differ between the HBD and NHBD-UROK Groups but was significantly higher in the NHBD Group than in the HBD Group (p = 0.032).


CONCLUSIONS
Adding urokinase into the perfusate during ex vivo evaluation resulted in improved graft function by reducing pulmonary vascular resistance and increasing oxygenation after 3 hours of warm ischemia. This ex vivo evaluation model is feasible and may be used to recondition grafts from NHBDs.
Inci
Ilhan
I
University Hospital, Division of Thoracic Surgery, University of Zurich, Zurich, Switzerland. ilhan.inci@usz.ch
Zhai
Wei
W
Arni
Stephan
S
Inci
Demet
D
Hillinger
Sven
S
Lardinois
Didier
D
Vogt
Peter
P
Weder
Walter
W
D000818:Animals; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006323:Heart Arrest; D001239:Inhalation; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016040:Lung Transplantation; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D011312:Pressure; D011651:Pulmonary Artery / Q000503:physiopathology; D013552:Swine; D013997:Time Factors; D014019:Tissue Donors; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D052096:Warm Ischemia
D005343:Fibrinolytic Agents; D014568:Urokinase-Type Plasminogen Activator; D010100:Oxygen