Modulation of endotoxin-induced cardiopulmonary dysfunction by S-nitroso-albumin.
J Endotoxin Res
; 8(1): 17-26, 2002.
Article
en En
| MEDLINE
| ID: mdl-11981442
Nitric oxide (NO) is an endogenous vasodilator and modulator of inflammation. During endotoxemia, the beneficial effects of NO are overwhelmed by the inflammatory cascade, resulting in a functional depletion of NO. S-nitroso-albumin (S-NO-alb) exists as a novel and highly stable NO thiol complex that slowly releases NO into the vascular micro-environment. Using a porcine model, we examined the ability of intravenous S-NO-alb to modulate cardiopulmonary dysfunction characteristic of endotoxemia. Pigs were anesthetized, instrumented for standard cardiopulmonary function measurements, and randomly assigned to receive: (i) albumin + saline; (ii) albumin + LPS; or (iii) S-NO-alb + LPS. Cardiopulmonary parameters were evaluated every 30 min and ex vivo phorbol myristate acetate (PMA)-stimulated superoxide release was serially determined as a marker of in vivo neutrophil priming. Lung myeloperoxidase (MPO) activity was measured as a marker of neutrophil migration into the lung. LPS-induced cardiopulmonary dysfunction was characterized by a sustained elevation in mean pulmonary arterial pressure, pulmonary vascular resistance, and peak intratracheal pressure, as well as a reduction in cardiac index, stroke volume index and PaO(2) over 6 h. Pretreatment with S-NO-alb attenuated LPS-induced cardiopulmonary dysfunction without adversely affecting systemic hemodynamics. Moreover, S-NO-alb blunted the LPS-induced hypoxemic response and reduced neutrophil activation. S-NO-alb did not, however, attenuate LPS-induced increases in lung MPO. Our results suggest that S-NO-alb can selectively modulate endotoxin-induced pulmonary dysfunction, attenuate neutrophil priming and block the early mortality (40%) in this model.
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Bases de datos:
MEDLINE
Asunto principal:
Albúmina Sérica Bovina
/
Lipopolisacáridos
/
Endotoxemia
/
Escherichia coli
/
Cardiopatías
/
Enfermedades Pulmonares
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Endotoxin Res
Asunto de la revista:
ANGIOLOGIA
/
BACTERIOLOGIA
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos