• M Theisen, K Träger, I Tugtekin, A Stehr, F Ploner, M Georgieff, P Radermacher, and M Matĕjovic.
• Sektion Anästhesiologische Pathophysiologie und Vefahrensentwicklung, Universitätsklinik für Anästhesiologie, Universität Ulm, Parkstrasse 11, 89073 Ulm, Germany.
• Intensive Care Med. 2001 Mar 1; 27 (3): 586-92.

ObjectiveTo 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.DesignProspective, randomized, controlled experimental study with repeated measures.SettingAnimal laboratory in a university hospital.SubjectsSixteen pigs, divided into two groups: nine endotoxemic animals without therapy (CON); seven animals treated with NIC.InterventionsPigs 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 ResultsAll 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.ConclusionsAlthough 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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