Human adrenomedullin and its binding protein attenuate organ injury and reduce mortality after hepatic ischemia-reperfusion.
Ann Surg
; 249(2): 310-7, 2009 Feb.
Article
en En
| MEDLINE
| ID: mdl-19212187
ABSTRACT
OBJECTIVE:
To determine whether administration of a vasoactive peptide, human adrenomedullin (AM), in combination with its binding protein (ie, AMBP-1), prevents or minimizes hepatic ischemia-reperfusion (I/R) injury. SUMMARY BACKGROUND DATA Hepatic I/R injury results from tissue hypoxia and subsequent inflammatory responses. Even though numerous pharmacological modalities and substances have been studied to reduce I/R-induced mortality, none have been entirely successful. We have shown that administration of AM/AMBP-1 produces significant beneficial effects under various pathophysiological conditions. However, it remains unknown if human AM/AMBP-1 has any protective effects on hepatic I/R-induced tissue damage and mortality.METHODS:
Seventy percent hepatic ischemia was induced in male adult rats by placing a microvascular clip across the hilum of the left and median lobes for 90 minutes. After removing the clip, human AM alone, human AMBP-1 alone, human AM in combination with human AMBP-1 or vehicle was administered intravenously over a period of 30 minutes. Blood and tissue samples were collected 4 hours after reperfusion for various measurements. In additional groups of animals, the nonischemic liver lobes were resected at the end of 90-minute ischemia. The animals were monitored for 7 days and survival was recorded.RESULTS:
After hepatic I/R, plasma levels of AM were significantly increased, whereas AMBP-1 levels were markedly decreased. Likewise, gene expression of AM in the liver was increased significantly, whereas AMBP-1 expression was markedly decreased. Administration of AM in combination with AMBP-1 immediately after the onset of reperfusion down-regulated inflammatory cytokines, decreased hepatic neutrophil infiltration, inhibited liver cell apoptosis and necrosis, and reduced liver injury and mortality in a rat model of hepatic I/R. On the other hand, administration of human AM alone or human AMBP-1 alone after hepatic I/R failed to produce significant protection.CONCLUSIONS:
Human AM/AMBP-1 may be a novel treatment to attenuate tissue injury after an episode of hepatic ischemia.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Vasodilatadores
/
Daño por Reperfusión
/
Factor H de Complemento
/
Adrenomedulina
/
Hígado
/
Hepatopatías
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Ann Surg
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA