Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-4-28
pubmed:abstractText
Overproduction of NO by an inducible NO synthase (iNOS) plays a role in the pathophysiology of septic shock. In such situations, NOS inhibition might be of therapeutic value, although detrimental side effects possibly related to inhibition of constitutive NOS have been reported. The use of L-canavanine, a selective inhibitor of iNOS, might be more suitable. The aim of the study was to compare in a rodent endotoxic shock the effects of saline (2 mL/h), N(G)-methyl-L-arginine(L-NMMA) (10 mg/kg/h) and L-canavanine (100 mg/kg/h) on muscle intracellular pH (pHi) and intracellular bioenergetic patterns (ATP, phosphocreatine/inorganic phosphate ratio) using in vivo 31P magnetic resonance spectroscopy (31P MRS). Three groups of anesthetized, mechanically ventilated and paralyzed rats received an intravenous infusion of 15 mg/kg of endotoxin. A fourth time-matched control group (n = 8) received 2 mL/h of saline. Mean arterial pressure, femoral blood flow, arterial blood gases, lactate, nitrate level, and 31P nuclear magnetic resonance (31P MRS) measurements were acquired at onset (T = 0), 90 min (T = 90), and 180 min (T180) after the endotoxin challenge. Femoral oxygen delivery was calculated as the product of femoral blood flow (mL/min) and arterial oxygen content. Endotoxin induced a marked decrease in arterial pressure and femoral oxygen delivery and an increase in lactate level. Intracellular pH and phosphocreatine/inorganic phosphate ratio decreased. ATP level did not change. Both L-NMMA and L-canavanine reversed the endotoxin-induced decrease in arterial pressure. L-NMMA attenuated the decrease in femoral oxygen delivery and the increase in lactate level while these were corrected by L-canavanine. Considering 31P MRS derived bioenergetic indices, the endotoxin-induced decrease in pHi and Pcr/Pi was attenuated by L-NMMA and corrected by L-canavanine. In conclusion, in a rodent model of endotoxinic shock, the continuous infusion of L-canavanine, a selective iNOS inhibitor, improved the systemic hemodynamic parameters and the intracellular bio-energetic patterns estimated by in vivo 31P MRS. To the contrary, the continuous infusion of both constitutive and inducible NOS inhibitor L-NMMA was not followed by the same achievement.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate, http://linkedlifedata.com/resource/pubmed/chemical/Canavanine, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Lactic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides, http://linkedlifedata.com/resource/pubmed/chemical/Nitrates, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II, http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Phosphates, http://linkedlifedata.com/resource/pubmed/chemical/Phosphocreatine, http://linkedlifedata.com/resource/pubmed/chemical/Phosphorus Isotopes, http://linkedlifedata.com/resource/pubmed/chemical/Sodium Chloride, http://linkedlifedata.com/resource/pubmed/chemical/omega-N-Methylarginine
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1073-2322
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
98-103
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10030795-Adenosine Triphosphate, pubmed-meshheading:10030795-Animals, pubmed-meshheading:10030795-Canavanine, pubmed-meshheading:10030795-Energy Metabolism, pubmed-meshheading:10030795-Enzyme Inhibitors, pubmed-meshheading:10030795-Hydrogen-Ion Concentration, pubmed-meshheading:10030795-Lactic Acid, pubmed-meshheading:10030795-Lipopolysaccharides, pubmed-meshheading:10030795-Muscle, Skeletal, pubmed-meshheading:10030795-Nitrates, pubmed-meshheading:10030795-Nitric Oxide Synthase, pubmed-meshheading:10030795-Nitric Oxide Synthase Type II, pubmed-meshheading:10030795-Phosphates, pubmed-meshheading:10030795-Phosphocreatine, pubmed-meshheading:10030795-Phosphorus Isotopes, pubmed-meshheading:10030795-Rats, pubmed-meshheading:10030795-Rats, Sprague-Dawley, pubmed-meshheading:10030795-Shock, Septic, pubmed-meshheading:10030795-Sodium Chloride, pubmed-meshheading:10030795-Spectrum Analysis, pubmed-meshheading:10030795-omega-N-Methylarginine
pubmed:year
1999
pubmed:articleTitle
Beneficial effects of L-canavanine, a selective inhibitor of inducible nitric oxide synthase, on lactate metabolism and muscle high energy phosphates during endotoxic shock in rats.
pubmed:affiliation
Service de Réanimation Médicale, Hôpital Central, Nancy, France. b.levy@chu-nancy.fr
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't