Effects of nicotinamide, an inhibitor of PARS activity, on gut and liver O2 exchange and energy metabolism during hyperdynamic porcine endotoxemia.
Intensive Care Med
; 27(3): 586-92, 2001 Mar.
Article
en En
| MEDLINE
| ID: mdl-11355130
OBJECTIVE: To investigate the effects of nicotinamide (NIC), an inhibitor of poly(ADP-ribose) synthetase (PARS), on intestinal and liver perfusion, O2 kinetics, and energy metabolism over 24 h of hyperdynamic porcine endotoxemia. DESIGN: Prospective, randomized, controlled experimental study with repeated measures. SETTING: Animal laboratory in a university hospital. SUBJECTS: Sixteen pigs, divided into two groups: nine endotoxemic animals without therapy (CON); seven animals treated with NIC. INTERVENTIONS: Pigs were anesthetized, mechanically ventilated, and instrumented. Intravenous E. Coli LPS was continuously infused over 24 h concomitant with fluid resuscitation. After 12 h of endotoxemia continuous i.v. infusion of NIC (10 mg/kg per hour) was administered until the end of the experiment. MEASUREMENTS AND RESULTS: All animals developed hyperdynamic circulation with sustained increase in cardiac output and progressive fall in mean arterial pressure. NIC maintained blood pressure without affecting CO. Hepato-splanchnic macrocirculation was not modified by the treatment. Nevertheless, although NIC attenuated the progressive rise of ileal mucosal-arterial PCO2 gap, it failed to improve portal venous L/P ratio, a marker of the overall energy state of the portal venous drained viscera. Similarly, neither the increased hepatic venous L/P ratio nor the simultaneous drop in hepatic lactate uptake were influenced by NIC. CONCLUSIONS: Although NIC maintained hemodynamic stabilization during long-term endotoxemia, it was unable to improve LPS-induced deterioration of the hepato-splanchnic energy metabolism. More potent and selective PARS inhibitors are needed to elucidate the role of a PARS-dependent pathway in a clinically relevant models of sepsis.
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Banco de datos:
MEDLINE
Asunto principal:
Consumo de Oxígeno
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Niacinamida
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Endotoxemia
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Modelos Animales de Enfermedad
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Metabolismo Energético
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Inhibidores de Poli(ADP-Ribosa) Polimerasas
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Mucosa Intestinal
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Intestinos
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Tipo de estudio:
Observational_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Intensive Care Med
Año:
2001
Tipo del documento:
Article
País de afiliación:
Alemania