Small-for-Size Liver Transplantation Increases Pulmonary Injury in Rats : Prevention by NIM811

Abstract EN

Pulmonary complications after liver transplantation (LT) often cause mortality.

This study investigated whether small-for-size LT increases acute pulmonary injury and whether NIM811 which improves small-for-size liver graft survival attenuates LT-associated lung injury.

Rat livers were reduced to 50% of original size, stored in UW-solution with and without NIM811 (5 μM) for 6 h, and implanted into recipients of the same or about twice the donor weight, resulting in half-size (HSG) and quarter-size grafts (QSG), respectively.

Liver injury increased and regeneration was suppressed after QSG transplantation as expected.

NIM811 blunted these alterations >75%.

Pulmonary histological alterations were minimal at 5–18 h after LT.

At 38 h, neutrophils and monocytes/macrophage infiltration, alveolar space exudation, alveolar septal thickening, oxidative/nitrosative protein adduct formation, and alveolar epithelial cell/capillary endothelial apoptosis became overt in the lungs of QSG recipients, but these alterations were mild in full-size and HSG recipients.

Liver pretreatment with NIM811 markedly decreased pulmonary injury in QSG recipients.

Hepatic TNFα and IL-1β mRNAs and pulmonary ICAM-1 expression were markedly higher after QSG transplantation, which were all decreased by NIM811.

Together, dysfunctional small-for-size grafts produce toxic cytokines, leading to lung inflammation and injury.

NIM811 decreased toxic cytokine formation, thus attenuating pulmonary injury after small-for-size LT.