Iloprost to improve surfactant function in porcine pulmonary grafts stored for twenty-four hours in low-potassium dextran solution.
OBJECTIVE
The optimal strategy for pulmonary graft preservation remains elusive. Experimental work and initial clinical experience support low-potassium dextran solutions as lung perfusates. We have previously shown a protective effect of prostaglandin E 1 on ischemia-reperfusion injury in lung transplantation by a shift from proinflammatory to anti-inflammatory cytokines in a rat lung transplantation model. In this study, we tested the hypothesis that the addition of a prostacyclin analog (iloprost) to low-potassium dextran might lead to improved surfactant and ultimately graft function.


METHODS
In a randomized, blinded study with a porcine left single-lung transplantation model, donor lungs were flushed with 1 L of either low-potassium dextran solution or low-potassium dextran solution modified by the addition of 250 microg iloprost (n = 6 in each group). Grafts were stored at 4 degrees C for 24 hours. After transplantation, the right bronchus and pulmonary artery were clamped, and the animals remained dependent on the graft. Posttransplantation graft function was assessed throughout a 7-hour observation period by measuring oxygenation (30-minute intervals), different pulmonary and systemic hemodynamic parameters, and wet/dry lung weight ratios. Bronchoalveolar lavage fluid was obtained before and 2 hours after reperfusion. Surfactant function was measured from bronchoalveolar lavage fluid with a pulsating bubble surfactometer. Neutrophil sequestration was assessed by a myeloperoxidase assay performed on lung tissue specimens taken at the end of the observation period.


RESULTS
Pulmonary vascular resistance remained lower in the iloprost group than in the control group (P < .05). Tissue water content after 7 hours of reperfusion remained lower in the iloprost group (P < .05). In addition, significantly reduced myeloperoxidase tissue activity was observed in the iloprost group (P < .05). Although there was no difference in degradation of surface active surfactant large aggregates to small aggregates, the surface tension measured at minimal bubble diameter was lower in the iloprost group (P < .05).


CONCLUSIONS
Modification of low-potassium dextran solution with the prostacyclin analog iloprost resulted in a significant amelioration of ischemia-reperfusion injury and improved preservation of surfactant function in transplanted lungs. This intriguing approach merits further evaluation with respect to the mechanisms involved and, ultimately, potential introduction into clinical lung transplantation.
Gohrbandt
Bernhard
B
Hannover Thoracic Transplant Program, Division of Thoracic and Cardiovascular Surgery, Hannover Medical School, Germany.
Sommer
Sebastian P
SP
Fischer
Stefan
S
Hohlfeld
Jens M
JM
Warnecke
Gregor
G
Haverich
Axel
A
Strueber
Martin
M
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D016285:Iloprost / Q000494:pharmacology*; D016040:Lung Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D011336:Probability; D011663:Pulmonary Surfactants; D011897:Random Allocation; D012016:Reference Values; D015427:Reperfusion Injury / Q000517:prevention & control*; D012680:Sensitivity and Specificity; D013500:Surface Tension / Q000187:drug effects; D013552:Swine
D019188:Organ Preservation Solutions; D011663:Pulmonary Surfactants; D009195:Peroxidase; D016285:Iloprost