Effects of a p38 mitogen-activated protein kinase inhibitor as an additive to XXXX -Collins solution on reperfusion injury in @entity235 lung transplantation1.

@entity63 @entity235 @entity26 @entity55910 @entity7634
BACKGROUND: The activation of p38 mitogen-activated protein kinase (MAPK) plays an important role in the development of @entity63 /reperfusion injury. @entity55910 is a novel p38 MAPK inhibitor. This study evaluated the effects of p38 MAPK inhibition during cold @entity63 on subsequent reperfusion injury using @entity55910 as an additive to @entity7634 -Collins solution in @entity235 lung transplantation. METHODS: @entity235 orthotopic left lung transplantation was performed after 12-hr cold storage using @entity7634 -Collins solution, with or without @entity55910 . Fifteen minutes after reperfusion, the right pulmonary artery and the right stem bronchus were ligated, and the animals were observed for 4 hr after reperfusion. Left pulmonary vascular resistance (L-PVR), cardiac output (CO), arterial @entity26 pressure (Pao2), and alveolar-arterial @entity26 pressure difference (A-aDo2) were measured. Lung specimens were harvested for wet-to-dry lung weight ratio (WDR) measurements, histopathologic studies, and polymorphonuclear neutrophil (PMN) counts. The activities of p38 MAPK in lung grafts were evaluated. RESULTS: The addition of @entity55910 significantly (P<0.05) improved Pao2, A-aDo2, L-PVR, CO, and WDR and suppressed PMN infiltration after transplantation. @entity55910 also ameliorated histologic damage to the lung graft. During cold storage, p38 MAPK was not activated in the lung graft, whereas it was markedly activated 30 min after reperfusion. @entity55910 significantly (P<0.05) inhibited p38 MAPK activation 30 min after reperfusion. CONCLUSIONS: The addition of @entity55910 to @entity7634 -Collins solution improved lung graft viability associated with the inhibition of p38 MAPK activation. These results suggest that inhibiting p38 MAPK activation may attenuate @entity63 /reperfusion injury in lung transplantation.
