Abstract | BACKGROUND: METHODS: Male Sprague-Dawley rats (n = 56) were randomly allocated into two groups: In the sepsis group, liver inflammation was established by injection of 56 mg/kg heat-killed Corynebacterium parvum; control rats received the solvent. At day 4, groups were subdivided according to treatment with the nitric oxide synthase inhibitor N(G)-monomethyl- L-arginine (250 mg/kg) or placebo. The aminopyrine breath test was performed to assess cytochrome P450 activity. Rats were anesthetized with propofol and mechanically ventilated. Duration of action of vecuronium (1.2 mg/kg) was measured by evoked mechanomyography (stimulation of the sciatic nerve, contraction of the gastrocnemius muscle). In seven rats of each subgroup a 50% neuromuscular blockade was established by a continuous vecuronium infusion. Vecuronium plasma levels were measured and plasma clearance of vecuronium was calculated. Nitric oxide synthesis was assessed by measuring nitrite/ nitrate serum levels. RESULTS: In sepsis/placebo rats, vecuronium-induced neuromuscular blockade was prolonged (144% of contro/placebo), vecuronium plasma levels at 50% neuromuscular blockade were increased (122% of control/placebo), and plasma clearance was decreased (68% of control/placebo). N(G)-monomethyl- L-arginine therapy in rats with sepsis improved cytochrome P450 activity and plasma clearance of vecuronium, shortened duration of action of vecuronium, but did not alter the elevated vecuronium plasma levels. CONCLUSIONS:
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Authors | M Blobner, E Kochs, H Fink, B Mayer, A Veihelmann, T Brill, J Stadler |
Journal | Anesthesiology
(Anesthesiology)
Vol. 91
Issue 4
Pg. 999-1005
(Oct 1999)
ISSN: 0003-3022 [Print] United States |
PMID | 10519503
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cytochrome P-450 Enzyme Inhibitors
- Enzyme Inhibitors
- Neuromuscular Nondepolarizing Agents
- Nitric Oxide
- Vecuronium Bromide
- Cytochrome P-450 Enzyme System
- Alanine Transaminase
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Topics |
- Alanine Transaminase
(biosynthesis)
- Animals
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Enzyme System
(metabolism)
- Disease Models, Animal
- Enzyme Inhibitors
(pharmacology)
- Gram-Positive Bacterial Infections
(drug therapy, enzymology, metabolism)
- Hepatitis, Animal
(enzymology, metabolism)
- Inactivation, Metabolic
- Male
- Neuromuscular Nondepolarizing Agents
(pharmacokinetics, pharmacology)
- Nitric Oxide
(biosynthesis)
- Propionibacterium acnes
- Rats
- Rats, Sprague-Dawley
- Systemic Inflammatory Response Syndrome
(drug therapy, enzymology, metabolism)
- Vecuronium Bromide
(pharmacokinetics, pharmacology)
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