Different Concentrations Of Isoflurane Research Articles

The Inhibitory Effects of Isoflurane on Protein Tyrosine Phosphorylation–modulated Contraction of Rat Aortic Smooth Muscle

Tyrosine kinase-catalyzed protein tyrosine phosphorylation plays an important role in initiating and modulating vascular smooth muscle contraction. The aim of the current study was to examine the effects of isoflurane on sodium orthovanadate (Na3VO4), a potent protein tyrosine phosphatase inhibitor-induced, tyrosine phosphorylation-mediated contraction of rat aortic smooth muscle. The Na3VO4-induced contraction of rat aortic smooth muscle and tyrosine phosphorylation of proteins including phospholipase Cgamma-1 (PLCgamma-1) and p44/p42 mitogen-activated protein kinase (MAPK) were assessed in the presence of different concentrations of isoflurane, using isometric force measurement and Western blotting methods, respectively. Na3VO4 (10(-4) m) induced a gradually sustained contraction and significant increase in protein tyrosine phosphorylation of a set of substrates including PLCgamma-1 and p42MAPK, all of which were markedly inhibited by genistein (5 x 10(-5) m), a tyrosine kinase inhibitor. Isoflurane (1.2-3.5%) dose-dependently depressed the Na3VO4-induced contraction (P < 0.05-0.005; n = 8). Isoflurane also attenuated the total density of the Na3VO4-induced, tyrosine-phosphorylated substrate bands and the density of tyrosine-phosphorylated PLCgamma-1 band and p42MAPK band (P < 0.05-0.005; n = 4) in a concentration-dependent manner. The findings of the current study, that isoflurane dose-dependently inhibits both the Na3VO4-stimulated contraction and tyrosine phosphorylation of a set of proteins including PLCgamma-1 and p42MAPK in rat aortic smooth muscle, suggest that isoflurane depresses protein tyrosine phosphorylation-modulated contraction of vascular smooth muscle, especially that mediated by the tyrosine-phosphorylated PLCgamma-1 and MAPK signaling pathways.

Cine-MRI assessment of cardiac function in mice anesthetized with ketamine/xylazine and isoflurane

Since small-animal MRI generally requires anesthesia, the effect of the anesthetic regimen on the explored organ(s) has to be taken into account for study interpretation. In this work, we assess the influence of ketamine/xylazine and isoflurane anesthesia on left-ventricular (LV) function in the mouse in vivo by cine-MRI. Three groups of animals were anesthetized with ketamine/xylazine (n = 13) and two different concentrations of isoflurane (1.25%, n = 12 and 2.00%, n = 12) delivered in O2/N2O mix. Long- and short-axis cine-MRI was performed to measure end-diastolic volume, stroke volume, ejection fraction and LV wall thickness. Ketamine/xylazine significantly reduced heart rate, cardiac output and wall thickness, but increased stroke volume and end-diastolic volume compared with both isoflurane groups. No differences across all groups were observed in ejection fraction or systolic wall thickening. Breath rate under isoflurane was significantly lower and concentration dependent, whereas heart function was independent of concentration in all measured parameters. These findings are in agreement with echocardiography and catheterization studies. Isoflurane is advantageous for MR studies because it better maintains cardiac function. Taking into account previously obtained myocardial perfusion measurements, isoflurane concentration should, however, be maintained at the minimum required for a stable sleep even if cardiac function is unaffected by higher isoflurane concentrations.

Concentration-dependent isoflurane effects on depolarization-evoked glutamate and GABA outflows from mouse brain slices.

The synaptic concentrations of glutamate and gamma-aminobutyric acid (GABA) are modulated by their release and re-uptake. The effects of general anaesthetics on these two processes remain unclear. This study evaluates the effects of isoflurane, a clinically important anaesthetic, on glutamate and GABA release and re-uptake in superfused mouse cerebrocortical slices. Experiments consisted of two 1.5-min exposures to 40 mM KCl in 30 min intervals. During the second exposure, different concentrations of isoflurane with and without 0.3 mM L-transpyrrolidine-2,4-dicarboxylic acid (PDC, a competitive inhibitor of glutamate uptake transporter) or 1 mM nipecotic acid (a competitive inhibitor of GABA uptake transporter) were introduced. The ratios of the second to first KCl-evoked increases in glutamate and GABA were used to determine the isoflurane concentration-response curves. The results can be described as a sum of two independent processes, corresponding to the inhibitions of release and re-uptake, respectively. The EC50 values for the inhibitions of release and re-uptake were 295+/-16 and 805+/-43 microM for glutamate, and 229+/-13 and 520+/-25 microM for GABA, respectively. Addition of PDC did not significantly affect glutamate release but shifted the re-uptake curve to the left (EC50= 315+/-20 microM). Nipecotic acid completely blocked GABA uptake, rendering isoflurane inhibition of GABA re-uptake undetectable. Our data suggest that isoflurane inhibits both the release and re-uptake of neurotransmitters and that the inhibitions occur at different EC50's. For GABA, both EC50's are within the clinical concentration range. The net anaesthetic effect on extracellular concentrations of neurotransmitters, particularly GABA, depends on the competition between inhibition of release and that of re-uptake.

Effects of Different Concentrations of Isoflurane on Core and Peripheral Temperature during General Anesthesia

Background : Precise temperature monitoring is essential during general anesthesia. Isoflurane induces vasodilation, which is correlated with changes in body temperature. The purpose of this study is to estimate the relationship between core temperature and peripheral body temperature which is usually used during anesthesia to determine changes in isoflurane concentration. Methods : Temperature measurements were performed in 46 patients of ASA physical status 1 or 2 undergoing oral & maxillofacial surgeries. During general anesthesia using isoflurane, body temperatures were measured every hour at the distal esophagus, the skin above the axillary artery and the rectum. Results : There was a weak linear relation between the changes of △Teso-axilla and isoflurane concentration, whereas there was no significant relation between the changes of △Teso-rectal and the isoflurane concentration. Conclusions : Axillary temperature was influenced by changes in isoflurane concentration, whereas the rectal temperature represented the core esophageal temperature during general anesthesia irrespective of changes in isoflurane concentration. (Korean J Anesthesiol 1999; 37: 745∼749)

Biotransformation of Isoflurane

The serum and urinary concentrations of fluorinated metabolites of isoflurane after inhalation of three different concentrations of isoflurane were studied in 18 ASA physical status 1 or 2 patients, scheduled for orthopedic or otolaryngeal surgery. Isoflurane was administered for 60 min during fentanyl-nitrous oxide-oxygen, and its end-tidal concentration was maintained at 0.3, 0.6, or 1.15% (groups I, II, and III). The organic fluorine was determined by combustion and fluoride ions were analyzed by ion chromatography. The amounts were expressed in terms of fluoride ion. The concentrations of serum fluoride ion and organic fluorine increased significantly 15 min after the onset of inhalation of isoflurane. The mean peak values of fluoride ions were 3.8 +/- 1.1, 3.9 +/- 1.4, and 4.2 +/- 0.9 mumole/1 (M +/- SD) in patients in groups I, II, and III, respectively. The half-lives of fluoride ion and of organic fluorine as metabolites of isoflurane, calculated from the amounts excreted in urine, were 36 h and 41 h, respectively. The cumulative amounts of fluoride ion and organic fluorine excreted up to the 6th postoperative day were 548 +/- 230 and 785 +/- 452 mumoles in group I, 594 +/- 138 and 1,378 +/- 807 mumoles in group II, and 1,032 +/- 496 and 728 +/- 265 mumoles (M +/- SD) in group III, respectively. The urinary excreted fluoride ion increased in proportion to the dose of isoflurane and approximately 1.3 mmol was excreted per 1 MAC X hour inhalation of isoflurane. The authors concluded that isoflurane might be biotransformed to a greater extent than reported previously, although the serum fluoride ion level was found to be low.