RESUMEN
BACKGROUND: Endothelial barrier dysfunction severely compromises organ function after reperfusion. Because dopamine pretreatment improves hypothermia mediated barrier dysfunction, we tested the hypothesis that dopamine treatment of lung allografts positively affects tissue damage associated with hypothermic preservation and reperfusion. METHODS: Rats were treated for 1 hr with dopamine (5 microg/min/kg) or vehicle (NaCl). Thereafter lungs were explanted, flushed with Perfadex solution and stored at 4 degrees C for different time periods. Peak inspiratory pressure (PIP), pulmonary arterial pressure (PAP), and lung weight were measured online during reperfusion. Inflammatory mediators in the perfusate and the expression of adhesion molecules in situ were measured after perfusion. RESULTS: Lungs could tolerate a cold ischemia time of up to 6 hr with stable PIP, PAP, and no edema formation upon reperfusion. Cold ischemia time above 6 hr significantly increased PIP, PAP, and pulmonary edema in untreated but not in dopamine treated lungs (P< or =0.001 dopamine treated vs. untreated). Perfusion and ventilation alone induced a strong up-regulation of cytokine-induced neutrophil chemoattractant-1 and adhesion molecules in untreated lungs, whereas in dopamine treated lungs significantly lower levels were found. Dopamine treatment also inhibited tissue damage associated with hypothermic preservation as measured by nicotinamide adenine dinucleotide staining. CONCLUSION: Our study suggests that donor dopamine treatment is a highly effective modality to maintain organ quality of lung allograft. These findings are of high clinical relevance because prevention of tissue damage might reduce complications associated with lung transplantation and hence improve graft survival in lung transplant recipients.