Pulmonary vascular clearance of harmful endogenous macromolecules in a porcine model of acute liver failure



Título del documento: Pulmonary vascular clearance of harmful endogenous macromolecules in a porcine model of acute liver failure
Revue: Annals of hepatology
Base de datos: PERIÓDICA
Número de sistema: 000411685
ISSN: 1665-2681
Autores: 1
2
3
4
5
6
2
7
1
Instituciones: 1University Hospital of Northern Norway, Department of Digestive Surgery, Troms, Tromso. Noruega
2University of Tromso, Department of Medical Biology, Troms, Tromso. Noruega
3Hospital de Clinicas de Porto Alegre, Unidade de Cirurgia, Porto Alegre, Rio Grande do Sul. Brasil
4University Hospital of Northern Norway, Department of Anesthesia and Intensive Care, Troms, Tromso. Noruega
5Universite de Montreal, Hepato-Neuro Laboratory, Montreal, Quebec. Canadá
6Luton & Dunstable University Hospital, Department of Gastroenterology, Luton. Reino Unido
7Royal Free Hospital, Institute of Liver and Digestive Health, Londres. Reino Unido
Año:
Periodo: May-Jun
Volumen: 15
Número: 3
Paginación: 427-435
País: México
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Experimental, analítico
Resumen en inglés Pulmonary complications are common in acute liver failure (ALF). The role of the lungs in the uptake of harmful soluble endogenous macromolecules was evaluated in a porcine model of ALF induced by hepatic devascularization (n = 8) vs. controls (n = 8). In additional experiments, pulmonary uptake was investigated in healthy pigs. Fluorochrome-labeled modified albumin (MA) was applied to investigate the cellular uptake. Results. Results. As Results. compared to controls, the ALF group displayed a 4-fold net increased lung uptake of hyaluronan, and 5-fold net increased uptake of both tissue plasminogen activator and lysosomal enzymes. Anatomical distribution experiments in healthy animals revealed that radiolabeled MA uptake (taken up by the same receptor as hyaluronan) was 53% by the liver, and 24% by the lungs. The lung uptake of LPS was 14% whereas 60% remained in the blood. Both fluorescence and electron microscopy revealed initial uptake of MA by pulmonary endothelial cells (PECs) with later translocation to pulmonary intravascular macrophages (PIMs). Moreover, the presence of PIMs was evident 10 min after injection. Systemic inflammatory markers such as leukopenia and increased serum TNF-α levels were evident after 20 min in the MA and LPS groups. Conclusion. Significant lung uptake of harmful soluble macromolecules compensated for the defect liver scavenger function in the ALF-group. Infusion of MA induced increased TNF-α serum levels and leukopenia, similar to the effect of the known inflammatory mediator LPS. These observations suggest a potential mechanism that may contribute to lung damage secondary to liver disease
Disciplinas: Medicina
Palabras clave: Gastroenterología,
Neumología,
Insuficiencia hepática aguda,
Síndrome de respuesta inflamatoria sistémica,
Acido hialurónico,
Células endoteliales,
Hígado,
Macrófagos,
Pulmones
Keyword: Medicine,
Gastroenterology,
Pneumology,
Acute liver failure,
Systemic inflammatory response syndrome,
Hyaluronic acid,
Endothelial cells,
Liver,
Macrophages,
Lungs
Texte intégral: Texto completo (Ver PDF)