当前位置： SCI文献检索 > INTENSIVE CARE MEDICINE期刊下所有文献 > Effects of nicotinamide, an inhibitor of PARS activity, on gut and liver O2 exchange and energy metabolism during hyperdynamic porcine endotoxemia.

Effects of nicotinamide, an inhibitor of PARS activity, on gut and liver O2 exchange and energy metabolism during hyperdynamic porcine endotoxemia.

Abstract：

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.

journal_name

Intensive Care Med

journal_title

Intensive care medicine

authors

Theisen M,Träger K,Tugtekin I,Stehr A,Ploner F,Georgieff M,Radermacher P,Matĕjovic M

doi

10.1007/s001340000842

keywords:

subject

Has Abstract

pub_date

2001-03-01 00:00:00

pages

586-92

issue

eissn

0342-4642

issn

1432-1238

journal_volume

pub_type

杂志文章

在线工具

Effects of nicotinamide, an inhibitor of PARS activity, on gut and liver O2 exchange and energy metabolism during hyperdynamic porcine endotoxemia.