Document Detail

N(G)-monomethyl-L-arginine improves survival in a pig model of abdominal sepsis.
MedLine Citation:
PMID:  9751584     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To test the effect of a continuous infusion of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on survival rate and hemodynamics in a pig model of endogenous peritoneal live bacterial sepsis. DESIGN: Prospective, randomized trial. SETTING: Laboratory at a university medical center. SUBJECTS: Thirty-five pigs with an average weight of 26 kg (range 21 to 33). INTERVENTIONS: After surgical preparation, animals (control, n=6) given anesthesia and fluids were observed for 9 hrs. Fifteen experimental animals received 0.5 g of cecal content/kg of body weight intraperitoneally after surgery. Nine of these animals received standard anesthesia and fluids and were observed for 9 hrs or until death. Six animals received a continuous infusion of L-NMMA (10 mg/kg/hr) 3 hrs after sepsis induction. Starting 3 hrs after surgery, five nonrandomized animals were given anesthesia and fluids and received a 6-hr continuous infusion of L-NMMA (10 mg/kg/hr). An additional nine animals were anesthetized and blood samples were taken to determine plasma nitrate concentrations in nonoperated pigs. MEASUREMENTS AND MAIN RESULTS: L-NMMA treatment increased 9-hr survival in septic animals from 11% to 83% (p < .001), prevented a further decrease in mean arterial pressure and restored mean arterial pressure to control levels (p < .00002 vs. nontreated septic animals). Mean pulmonary arterial pressure increased slightly during L-NMMA infusion (p < .0003). Coronary blood flow was preserved during L-NMMA treatment. Cardiac index and urine production reached and maintained control levels during L-NMMA treatment of septic animals. Mean central venous pH did not deteriorate during L-NMMA treatment. Animals treated with L-NMMA had plasma nitrate concentrations similar to nonseptic control animals. The results from the nonseptic control group receiving L-NMMA suggest that a substantial part of the effect of L-NMMA in this model of septic shock may be due to inhibition of the constitutive nitric oxide production. CONCLUSIONS: In this porcine model of peritoneal sepsis, infusion of L-NMMA increased survival rate and maintained mean arterial pressure without worsening tissue oxygenation. Coronary blood flow, cardiac index, systemic vascular resistance, and urine production were well maintained during L-NMMA treatment.
O A Strand; A M Leone; K E Giercksky; E Skovlund; K A Kirkebøen
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Critical care medicine     Volume:  26     ISSN:  0090-3493     ISO Abbreviation:  Crit. Care Med.     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1998-10-08     Completed Date:  1998-10-08     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1490-9     Citation Subset:  AIM; IM    
Department of Infectious Diseases, Institute for Experimental Medical Research, Ullevål University Hospital, Oslo, Norway.
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MeSH Terms
Bacteremia / drug therapy*,  physiopathology
Critical Care
Disease Models, Animal
Enzyme Inhibitors / administration & dosage*
Hemodynamics / drug effects
Nitrates / blood
Nitric Oxide Synthase / antagonists & inhibitors*
Peritonitis / drug therapy*,  physiopathology
Prospective Studies
Random Allocation
omega-N-Methylarginine / administration & dosage*
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Nitrates; 17035-90-4/omega-N-Methylarginine; EC Oxide Synthase
Comment In:
Crit Care Med. 2000 Jan;28(1):287-8   [PMID:  10667557 ]
Crit Care Med. 1998 Sep;26(9):1469-70   [PMID:  9751571 ]
Erratum In:
Crit Care Med 1999 Jan;27(1):226
Crit Care Med 1999 Feb;27(2):444

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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