OBJECTIVE: To investigate whether pyrrolidinone derivative (N2733), an inhibitor of nuclear factor (NF)-kappaB activation, improves altered metabolic and hemodynamic changes and organ dysfunctions caused by endotoxic shock. DESIGN AND SETTING: Prospective, randomized, animal study in a laboratory at a university hospital. SUBJECTS: Twenty-three anesthetized male beagle dogs (10-14 kg). INTERVENTIONS: Dogs were mechanically ventilated and monitored with a pulmonary arterial catheter and a gastric tonometer. A central venous catheter was inserted into the femoral vein, and lactated Ringer's solution (10 ml/kg per hour) was administered throughout the study period. Three groups of animals were studied: (a) the lipopolysaccharide (LPS) group (n=8), which received LPS (250 ng/kg per minute for 2 h); (b) the LPS plus N2733 group (n=8), which received N2733 (30 mg/kg intravenously and 10 mg/kg hour for 6 h) after the start of LPS; and (c) the N2733 group (n=7), which received N2733 (30 mg/kg intravenously and 10 mg/kg per hour for 6 h). MEASUREMENTS AND RESULTS: Changes in hemodynamics, blood gas, gastric intramural pH, and renal and hepatic function were measured for 6 h. Coadministration of N2733 increased oxygen delivery index and prevented the LPS-induced hypotension, metabolic acidosis, and gastric mucosal acidosis but did not affect renal or hepatic function. CONCLUSIONS: Administration of N2733 increased oxygen delivery index and prevented the LPS-induced hypotension and metabolic and gastric mucosal acidosis in an anesthetized canine endotoxic shock model, suggesting its beneficial effect on local blood flow against tissue hypoxia. These findings suggest that blockade of NF-kappaB activation prevents hypodynamic shock and gastric hypoperfusin in endotoxic shock.
OBJECTIVE: To investigate whether pyrrolidinone derivative (N2733), an inhibitor of nuclear factor (NF)-kappaB activation, improves altered metabolic and hemodynamic changes and organ dysfunctions caused by endotoxic shock. DESIGN AND SETTING: Prospective, randomized, animal study in a laboratory at a university hospital. SUBJECTS: Twenty-three anesthetized male beagle dogs (10-14 kg). INTERVENTIONS:Dogs were mechanically ventilated and monitored with a pulmonary arterial catheter and a gastric tonometer. A central venous catheter was inserted into the femoral vein, and lactated Ringer's solution (10 ml/kg per hour) was administered throughout the study period. Three groups of animals were studied: (a) the lipopolysaccharide (LPS) group (n=8), which received LPS (250 ng/kg per minute for 2 h); (b) the LPS plus N2733 group (n=8), which received N2733 (30 mg/kg intravenously and 10 mg/kg hour for 6 h) after the start of LPS; and (c) the N2733 group (n=7), which received N2733 (30 mg/kg intravenously and 10 mg/kg per hour for 6 h). MEASUREMENTS AND RESULTS: Changes in hemodynamics, blood gas, gastric intramural pH, and renal and hepatic function were measured for 6 h. Coadministration of N2733 increased oxygen delivery index and prevented the LPS-induced hypotension, metabolic acidosis, and gastric mucosal acidosis but did not affect renal or hepatic function. CONCLUSIONS: Administration of N2733 increased oxygen delivery index and prevented the LPS-induced hypotension and metabolic and gastric mucosal acidosis in an anesthetized canineendotoxic shock model, suggesting its beneficial effect on local blood flow against tissue hypoxia. These findings suggest that blockade of NF-kappaB activation prevents hypodynamic shock and gastric hypoperfusin in endotoxic shock.
Authors: H Böhrer; F Qiu; T Zimmermann; Y Zhang; T Jllmer; D Männel; B W Böttiger; D M Stern; R Waldherr; H D Saeger; R Ziegler; A Bierhaus; E Martin; P P Nawroth Journal: J Clin Invest Date: 1997-09-01 Impact factor: 14.808
Authors: Salvatore Cuzzocrea; Antonietta Rossi; Barbara Pisano; Rosanna Di Paola; Tiziana Genovese; Nimesh S A Patel; Elisabetta Cuzzocrea; Angela Ianaro; Lidia Sautebin; Francesco Fulia; Prabal K Chatterjee; Achille P Caputi; Christoph Thiemermann Journal: Intensive Care Med Date: 2003-07-17 Impact factor: 17.440
Authors: Peter Andrews; Elie Azoulay; Massimo Antonelli; Laurent Brochard; Christian Brun-Buisson; Geoffrey Dobb; Jean-Yves Fagon; Herwig Gerlach; Johan Groeneveld; Jordi Mancebo; Philipp Metnitz; Stefano Nava; Jerome Pugin; Michael Pinsky; Peter Radermacher; Christian Richard; Robert Tasker Journal: Intensive Care Med Date: 2006-02-18 Impact factor: 17.440
Authors: Balázs Hauser; Jochen Kick; Zsolt Iványi; Pierre Asfar; Ulrich Ehrmann; Claus-Martin Muth; Maura Albicini; Ulrich Wachter; Josef Vogt; Michael Bauer; Uwe Bernd Brückner; Peter Radermacher; Hendrik Bracht Journal: Intensive Care Med Date: 2006-03-14 Impact factor: 17.440