title: The negative inotropic effect of sevoflurane is not mediated through nitric oxide synthase in rat papillary muscle.
abstract: Sevoflurane has dose-dependent negative inotropic effects on myocardial contractility. The current study investigated whether the nitric oxide pathway is involved in these effects. A laboratory, ex-vivo experiment was performed on 66 isolated papillary muscles. Effects of increasing concentrations of sevoflurane (1, 2 and 3 MAC) were assessed in control conditions, in the presence of Nw-nitro-L-arginine (L-NOARG) and in beta-adrenergic stimulated rat papillary muscles. Contractility was assessed by total developed tension. In baseline conditions, the administration of increasing concentrations of sevoflurane caused a dose-dependent reduction in contractility of respectively 8.6 +/- 1.7%, 14.4 +/- 4.8% and 23.6 +/- 3.9%. This negative inotropic effect was not significantly altered by the administration of the NO-synthase inhibitor L-NOARG (p = 0.09). Under continuous administration of 3 MAC sevoflurane, 4 consecutive concentrations of isoproterenol induced a mean increase of contractility of respectively 43.0 +/- 13.7%, 65.9 +/- 22.6%, 131.2 +/- 25.6% and 122.3 +/- 31.2%. After administration of L-NOARG, the 4 consecutive concentrations of isoproterenol induced a mean increase in contractility of respectively 36.0 +/- 8.5%, 75.0 +/- 17.8%, 143.0 +/- 42.8% and 120.0 +/- 51.4% (p = 0.85). These data indicated that the negative inotropic effects of sevoflurane in rat papillary muscles, both in basic as in beta-adrenergic stimulated conditions, were not altered by blocking the NO-cGMP-system.
authors.affiliation: Department of Anesthesiology, University Hospital of Antwerp, Antwerp, Belgium.
authors.forename: P V
authors.initials: PV
authors.lastname: Lecomte
authors.forename: A
authors.initials: A
authors.lastname: Hacker
authors.forename: G
authors.initials: G
authors.lastname: Kojda
authors.forename: S G
authors.initials: SG
authors.lastname: De Hert
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane
chemical_list: D000318:Adrenergic beta-Agonists; D018685:Anesthetics, Inhalation; D000889:Anti-Arrhythmia Agents; D004791:Enzyme Inhibitors; D008738:Methyl Ethers; D019335:Nitroarginine; D000077149:Sevoflurane; D019001:Nitric Oxide Synthase; D007545:Isoproterenol