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Effects of volatile anesthetics on atrial and AV nodal electrophysiological properties in guinea pig isolated perfused heart.

BACKGROUND: Knowledge of the anesthetic effects on atrial and atrioventricular (AV) nodal electrophysiologic properties is fundamental to understand the modulatory role of anesthetics on the pathogenesis of supraventricular tachycardias, and to individualize the perioperative management of patients with supraventricular tachycardias or AV nodal conduction disturbances. Therefore the authors studied the effects of three commonly used volatile anesthetics on the electrophysiologic properties of the atrium and AV node. METHODS: The concentration-dependent electrophysiologic effects of halothane, isoflurane, and desflurane (0-2 minimum alveolar concentration [MAC]) were studied in guinea pig Langendorff-perfused hearts fit with instruments to simultaneously measure atrial and AV nodal conduction times and atrial monophasic action potential duration. Atrial and AV nodal effective refractory periods were measured simultaneously using a computer-assisted premature stimulation protocol. The concentrations of anesthetics in the gas phase were monitored by an infrared gas analyzer. RESULTS: Volatile anesthetics caused markedly different concentration-dependent effects on atrial conduction, repolarization, and refractoriness, and on AV nodal function. At equianesthetic concentrations, halothane depressed atrial conduction the most, whereas desflurane caused the greatest shortening of atrial monophasic action potential duration. Halothane had no significant effect on atrial refractoriness, whereas at 2 MAC desflurane significantly shortened and isoflurane significantly prolonged atrial effective refractory periods by 18.1+/-13.5% and 13.2+/-14.7%, respectively. On an equi-MAC basis, the rank order of potency for the anesthetics to prolong AV nodal conduction time and AV nodal ERP was halothane > desflurane > isoflurane. CONCLUSION: The different electrophysiologic effects of volatile anesthetics in the atrium and AV node suggest that these agents may modulate atrial dysrhythmogenesis in distinctly different ways.

Action Potentials↗

Inhibitory effects of volatile anesthetics on K+ and Cl- channel currents in porcine tracheal and bronchial smooth muscle.

BACKGROUND: K+ and Ca2+-activated Cl- (ClCa) channel currents have been shown to contribute to the alteration of membrane electrical activity in airway smooth muscle. This study was conducted to investigate the effects of volatile anesthetics, which are potent bronchodilators, on the activities of these channels in porcine tracheal and bronchial smooth muscles. METHODS: Whole-cell patch clamp recording techniques were used to investigate the effects of superfused isoflurane (0-1.5 minimum alveolar concentration) or sevoflurane (0-1.5 minimum alveolar concentration) on K+ and ClCa channel currents in dispersed smooth muscle cells. RESULTS: Isoflurane and sevoflurane inhibited whole-cell K+ currents to a greater degree in tracheal versus bronchial smooth muscle cells. More than 60% of the total K+ currents in tracheal smooth muscle appeared to be mediated through delayed rectifier K+ channels compared with less than 40% in bronchial smooth muscle. The inhibitory effects of the anesthetics were greater on the delayed rectifier K+ channels than on the remaining K+ channels. Cl- currents through ClCa channels were significantly inhibited by the anesthetics. The inhibitory potencies of the anesthetics on the ClCa channels were not different in tracheal and bronchial smooth muscle cells. CONCLUSIONS: Volatile anesthetics isoflurane and sevoflurane significantly inhibited Cl- currents through ClCa channels, and the inhibitory effect is consistent with the relaxant effect of volatile anesthetics in airway smooth muscle. Different distributions and different anesthetic sensitivities of K+ channel subtypes could play a role in the different inhibitory effects of the anesthetics on tracheal and bronchial smooth muscle contractions.

4-Aminopyridine↗

Effects of volatile anesthetics on store-operated Ca(2+) influx in airway smooth muscle.

BACKGROUND: In airway smooth muscle (ASM), volatile anesthetics deplete sarcoplasmic reticulum (SR) Ca(2+) stores by increasing Ca(2+) "leak." Accordingly, SR replenishment becomes dependent on Ca(2+) influx. Depletion of SR Ca(2+) stores triggers Ca(2+) influx via specific plasma membrane channels, store-operated Ca(2+) channels (SOCC). We hypothesized that anesthetics inhibit SOCC triggered by increased SR Ca(2+) "leak," preventing SR replenishment and enhancing ASM relaxation. METHODS: In porcine ASM cells, SR Ca was depleted by cyclopiazonic acid or caffeine in 0 extracellular Ca(2+), nifedipine and KCl (preventing Ca(2+) influx through L-type and SOCC channels). Extracellular Ca(2+) was rapidly introduced to selectively activate SOCC. After SOCC activation, SR was replenished and the protocol repeated in the presence of 1 or 2 minimum alveolar concentration halothane, isoflurane, or sevoflurane. In other cells, characteristics of SOCC and interactions between acetylcholine (Ach) and volatile anesthetics were examined. RESULTS: Cyclopiazonic acid produced slow SR leak, whereas the caffeine response was transient in ASM cells. Reintroduction of extracellular Ca(2+) rapidly increased [Ca(2+)]i. This influx was insensitive to nifedipine, SKF-96365, and KBR-7943, inhibited by Ni and blockade of inositol 1,4,5-triphosphate-induced SR Ca(2+) release, and enhanced by ACh. Preexposure to 1 or 2 minimum alveolar concentration halothane completely inhibited Ca(2+) influx when extracellular Ca(2+) was reintroduced, whereas isoflurane and sevoflurane produced less inhibition. Only halothane and isoflurane inhibited ACh-induced augmentation of Ca(2+) influx. CONCLUSION: Volatile anesthetics inhibit a Ni/La-sensitive store-operated Ca(2+) influx mechanism in porcine ASM cells, which likely helps maintain anesthetic-induced bronchodilation.

Acetylcholine↗

Volatile anesthetics bind rat synaptic snare proteins.

BACKGROUND: Volatile general anesthetics (VAs) have a number of synaptic actions, one of which is to inhibit excitatory neurotransmitter release; however, no presynaptic VA binding proteins have been identified. Genetic data in Caenorhabditis elegans have led to the hypothesis that a protein that interacts with the presynaptic protein syntaxin 1A is a VA target. Motivated by this hypothesis, the authors measured the ability of syntaxin 1A and proteins that interact with syntaxin to bind to halothane and isoflurane. METHODS: Recombinant rat syntaxin 1A, SNAP-25B, VAMP2, and the ternary SNARE complex that they form were tested. Binding of VAs to these proteins was detected by F-nuclear magnetic resonance relaxation measurements. Structural alterations in the proteins were examined by circular dichroism and ability to form complexes. RESULTS: Volatile anesthetics did not bind to VAMP2. At concentrations in the clinical range, VAs did bind to SNAP-25B; however, binding was detected only in preparations containing SNAP-25B homomultimers. VAs also bound at clinical concentrations to both syntaxin and the SNARE complex. Addition of an N-terminal His6 tag to syntaxin abolished its ability to bind VAs despite normal secondary structure and ability to form SNARE complexes; thrombin cleavage of the tag restored VA binding. Thus, the VA binding site(s) has structural requirements and is not simply any alpha-helical bundle. VAs at supraclinical concentrations produced an increase in helicity of the SNARE complex; otherwise, VA binding produced no gross alteration in the stability or secondary structure of the SNARE complex. CONCLUSION: SNARE proteins are potential synaptic targets of volatile anesthetics.

Anesthetics, Inhalation↗

Store-operated Ca2+ influx in airway smooth muscle: Interactions between volatile anesthetic and cyclic nucleotide effects.

BACKGROUND: Volatile anesthetics produce bronchodilation in part by depleting sarcoplasmic reticulum Ca stores in airway smooth muscle (ASM). Other bronchodilatory drugs are known to act via cyclic nucleotides (cyclic adenosine 3',5'-cyclic monophosphate, cyclic guanosine 3',5'-cyclic monophosphate). Intracellular Ca regulation in ASM involves plasma membrane Ca influx, including that triggered by sarcoplasmic reticulum Ca depletion (store-operated Ca entry [SOCE]). The authors hypothesized that anesthetics and bronchodilatory agents interact in inhibiting SOCE, thus enhancing ASM relaxation. METHODS: In enzymatically dissociated porcine ASM cells imaged using fluorescence microscopy, sarcoplasmic reticulum Ca was depleted by 1 microm cyclopiazonic acid in 0 extracellular Ca, nifedipine, and potassium chloride (preventing Ca influx through L-type channels and SOCE). Extracellular Ca was rapidly reintroduced to selectively activate SOCE in the presence or absence of 1 minimum alveolar concentration (MAC) halothane, isoflurane, or sevoflurane. Anesthetic interference with SOCE regulation by cyclic nucleotides was examined by activating SOCE in the presence of (1) 1 microm acetylcholine, (2) 100 microm dibutryl cyclic adenosine 3',5'-cyclic monophosphate, or (3) 100 microm 8-bromo-cyclic guanosine 3',5'-cyclic monophosphate. RESULTS: SOCE was enhanced by acetylcholine, whereas volatile anesthetics and both cyclic nucleotides partially inhibited Ca influx. Preexposure to 1 or 2 MAC anesthetic (halothane > isoflurane > sevoflurane) inhibited SOCE. Only halothane and isoflurane inhibited acetylcholine-induced augmentation of Ca influx, and significantly potentiated cyclic nucleotide inhibition such that no influx was observed in the presence of anesthetics and cyclic nucleotides. CONCLUSIONS: These data indicate that volatile anesthetics prevent sarcoplasmic reticulum refilling by inhibiting SOCE and enhancing cyclic nucleotide blunting of Ca influx in ASM. Such interactions likely result in substantial airway relaxation in the presence of both anesthetics and bronchodilatory agents such as beta agonists or nitric oxide.

Acetylcholine↗

Volatile anaesthetics induce changes in the expression of P-selectin and glycoprotein Ib on the surface of platelets in vitro.

Halothane has been shown to inhibit platelet aggregation and may, therefore, prevent intraoperative platelet activation. The aim of this study was to compare the effects of volatile anaesthetics on platelet activation, including the transformation into an adhesive platelet phenotype. After in vitro exposure to volatile anaesthetics, the expression of the adhesion molecule P-selectin and the internalization of the receptor for the von Willebrand factor (GPlb) were analysed by flow cytometry. In contrast to desflurane or N2O, sevoflurane (> or = 0.5 MAC, P < 0.05), halothane (> or = 1.0 MAC, P < 0.01) and isoflurane (> or = 2.0 MAC, P < 0.01) induced a significantly higher expression of P-selectin on the surface of platelets, indicating the degranulation of alpha-granules. In the presence of desflurane (> or = 0.5 MAC, P < 0.05), halothane (> or = 1.0 MAC, P < 0.01), isoflurane and sevoflurane (both > or = 2.0 MAC, P < 0.01), a redistribution of GPlb occurred, indicating platelet activation. N2O had no effect. In conclusion, several of the volatile anaesthetics tested in vitro induced changes in the expression of P-selectin and GPlb, being characteristic of platelet activation. None of the anaesthetics investigated interfered with the platelet response to ADP stimulation.

Adult↗

Evidence for a role of volatile amines in the development of neonatal hypergastrinemia.

We investigated the presence of volatile aliphatic amines by fluorescamine and gas chromatographic-head space analysis in human breast milk and amniotic fluid to assess their role in neonatal hypergastrinemia. These volatile nitrogenous amino acid metabolites have been previously demonstrated to stimulate gastrin release in in vivo and in vitro laboratory preparations. In the present study we demonstrated that these gastrin-stimulatory volatile amines were present in significant concentrations in breast milk during the first several weeks after parturition and in amniotic fluid. The individual amines that were identified in both human milk and amniotic fluid samples were methylamine, dimethylamine, ethylamine, trimethylamine, propylamine, isobutylamine, and butylamine. This study provides indirect evidence to support the possibility that the hypergastrinemia measured in the fetus/neonate during the period immediately before and after birth may be attributable, in part, to the ingestion of fluid containing high concentrations of gastrin-stimulating amines.

Amines↗

Reduced heart rate volatility: an early predictor of death in trauma patients.

OBJECTIVE: To determine if using dense data capture to measure heart rate volatility (standard deviation) measured in 5-minute intervals predicts death. BACKGROUND: Fundamental approaches to assessing vital signs in the critically ill have changed little since the early 1900s. Our prior work in this area has demonstrated the utility of densely sampled data and, in particular, heart rate volatility over the entire patient stay, for predicting death and prolonged ventilation. METHODS: Approximately 120 million heart rate data points were prospectively collected and archived from 1316 trauma ICU patients over 30 months. Data were sampled every 1 to 4 seconds, stored in a relational database, linked to outcome data, and de-identified. HR standard deviation was continuously computed over 5-minute intervals (CVRD, cardiac volatility-related dysfunction). Logistic regression models incorporating age and injury severity score were developed on a test set of patients (N = 923), and prospectively analyzed in a distinct validation set (N = 393) for the first 24 hours of ICU data. RESULTS: Distribution of CVRD varied by survival in the test set. Prospective evaluation of the model in the validation set gave an area in the receiver operating curve of 0.81 with a sensitivity and specificity of 70.1 and 80.0, respectively. CVRD predict death as early as 24 hours in the validation set. CONCLUSIONS: CVRD identifies a subgroup of patients with a high probability of dying. Death is predicted within first 24 hours of stay. We hypothesize CVRD is a surrogate for autonomic nervous system dysfunction.

Adult↗

Best linear forecast of volatility in financial time series.

The autocorrelation function of volatility in financial time series is fitted well by a superposition of several exponents. This case admits an explicit analytical solution of the problem of constructing the best linear forecast of a stationary stochastic process. We describe and apply the proposed analytical method for forecasting volatility. The leverage effect and volatility clustering are taken into account. Parameters of the predictor function are determined numerically for the Dow Jones 30 Industrial Average. Connection of the proposed method to the popular autoregressive conditional heteroskedasticity models is discussed.

Journal Article↗

Scaling and memory of intraday volatility return intervals in stock markets.

We study the return interval tau between price volatilities that are above a certain threshold q for 31 intraday data sets, including the Standard and Poor's 500 index and the 30 stocks that form the Dow Jones Industrial index. For different threshold q, the probability density function Pq(tau)scales with the mean interval tau as [Formula: see text], similar to that found in daily volatilities. Since the intraday records have significantly more data points compared to the daily records, we could probe for much higher thresholds and still obtain good statistics. We find that the scaling function f(x)is consistent for all 31 intraday data sets in various time resolutions, and the function is well-approximated by the stretched exponential, f(x) similar to e(-ax)(gamma), with gamma=0.38+/-0.05 and a=3.9+/-0.5, which indicates the existence of correlations. We analyze the conditional probability distribution Pq(tau/tau0) for tau following a certain interval tau0, and find Pq(tau/tau0) depends on tau0, which demonstrates memory in intraday return intervals. Also, we find that the mean conditional interval (tau/tau0) increases with tau0, consistent with the memory found for Pq(tau/tau0). Moreover, we find that return interval records, in addition to having short-term correlations as demonstrated by Pq(tau/tau0), have long-term correlations with correlation exponents similar to that of volatility records.

Journal Article↗

Return-volatility correlation in financial dynamics.

We investigate the return-volatility correlation both local and nonlocal in time with daily and minutely data of the German DAX and Chinese indices, and observe a leverage effect for the German DAX, while an antileverage effect for the Chinese indices. In the negative time direction, i.e., for the volatility-return correlation, an antileverage effect nonlocal in time is detected for both the German DAX and Chinese indices, although the duplicate local in time does not exist. A retarded volatility model may describe the asymmetric properties of the financial indices in the positive time direction.

Journal Article↗

Circadian regulation of the PhCCD1 carotenoid cleavage dioxygenase controls emission of beta-ionone, a fragrance volatile of petunia flowers.

Carotenoids are thought to be the precursors of terpenoid volatile compounds that contribute to flavor and aroma. One such volatile, beta-ionone, is important to fragrance in many flowers, including petunia (Petunia hybrida). However, little is known about the factors regulating its synthesis in vivo. The petunia genome contains a gene encoding a 9,10(9',10') carotenoid cleavage dioxygenase, PhCCD1. The PhCCD1 is 94% identical to LeCCD1A, an enzyme responsible for formation of beta-ionone in tomato (Lycopersicon esculentum; Simkin AJ, Schwartz SH, Auldridge M, Taylor MG, Klee HJ [2004] Plant J [in press]). Reduction of PhCCD1 transcript levels in transgenic plants led to a 58% to 76% decrease in beta-ionone synthesis in the corollas of selected petunia lines, indicating a significant role for this enzyme in volatile synthesis. Quantitative reverse transcription-PCR analysis revealed that PhCCD1 is highly expressed in corollas and leaves, where it constitutes approximately 0.04% and 0.02% of total RNA, respectively. PhCCD1 is light-inducible and exhibits a circadian rhythm in both leaves and flowers. beta-Ionone emission by flowers occurred principally during daylight hours, paralleling PhCCD1 expression in corollas. The results indicate that PhCCD1 activity and beta-ionone emission are likely regulated at the level of transcript.

Amino Acid Sequence↗

Volatile Semiochemicals Released from Undamaged Cotton Leaves (A Systemic Response of Living Plants to Caterpillar Damage).

Cotton plants (Gossypium hirsutum L.), attacked by herbivorous insects release volatile semiochemicals (chemical signals) that attract natural enemies of the herbivores to the damaged plants. We found chemical evidence that volatiles are released not only at the damaged site but from the entire cotton plant. The release of volatiles was detected from upper, undamaged leaves after 2 to 3 d of continuous larval damage on lower leaves of the same plant. Compounds released systemically were (Z)-3-hexenyl acetate, (E)-[beta]-ocimene, linalool, (E)-4,8-dimethyl-1,3,7-nonatriene, (E)-[beta]-farnesene, (E,E)-[alpha]-farnesene, and (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene. All systemically released compounds are known to be induced by caterpillar damage and are not released in significant amounts by undamaged plants. Other compounds, specifically indole, isomeric hexenyl butyrates, and 2-methylbutyrates, known to be released by cotton in response to caterpillar damage, were not released systemically. However, when upper, undamaged leaves of a caterpillar-damaged plant were damaged with a razor blade, they released isomeric hexenyl butyrates, 2-methylbutyrates, and large amounts of constitutive compounds in addition to the previously detected induced compounds. Control plants, damaged with a razor blade in the same way, did not release isomeric hexenyl butyrates or 2-methylbutyrates and released significantly smaller amounts of constitutive compounds. Indole was not released systemically, even after artificial damage.

Journal Article↗

Evaluation of the allergic/irritant potential of air pollutants: detection of proteins modified by volatile organic compounds from oilseed rape (Brassica napus ssp. oleifera) using electrospray ionization-mass spectrometry.

BACKGROUND: Upward trends in allergy and asthma rates have been reported in most western societies, including the UK, where around 15-20% of the population now suffer from allergy or asthma. Scientific proof of the causes of these increases relies on accurate assessment of exposure and standardized diagnostic tests, such as for specific IgE in blood serum and skin testing. For many air pollutants it has proven difficult to assess an individual's exposure outside an occupational environment and reliable test development is hampered by not knowing whether an allergic or irritant mechanism is involved. These problems are particularly evident in the controversial issue of whether airborne releases from oilseed rape can cause health effects. OBJECTIVE: To develop a method for evaluating the allergic/irritant potential of air pollutants and to assess whether the volatile organic compounds emitted by oilseed rape have this potential. METHODS: Proteins were exposed in vitro to volatile organic compounds emitted by oilseed rape. Electrospray ionization-mass spectrometry was used to detect any resultant protein modifications. RESULTS: Dimethyl disulphide, thiocyanic acid methyl ester and 2-methyl-propanenitrile were able to modify human proteins. In addition, two isothiocyanates which can be emitted by damaged oilseed rape also have this ability. The major products emitted by undamaged oilseed rape, terpenes, a sesquiterpene and a terpene alcohol did not have this property, but the possible role of their oxidized products is discussed. CONCLUSION: Some of the volatile organic compounds emitted by oilseed rape have the potential to be allergens/irritants. Standardized modified proteins produced by this method should prove useful for biomonitoring human exposure in molecular epidemiological studies as well as in diagnostic tests. This method should find further application in investigations into the possible health effects of other environmental pollutants.

Air Pollutants↗

Effect of substrate on the production of antifungal volatiles from Bacillus subtilis.

An antibiotic-producing strain of Bacillus subtilis has been shown to produce potent antifungal volatiles (AFV). These volatiles are active against a range of fungal species and are produced on a range of growth media and in loam-based compost. In vitro antifungal volatile activity on nutrient agar is enhanced with the addition of D-glucose, complex carbohydrates and peptones. The addition of L-glucose led to significantly less AFV activity than comparable levels of D-glucose. Growth studies in liquid culture revealed that B. subtilis failed to grow in response to L-glucose. Further growth studies on solid media showed no clear correlation between enhanced bacterial growth and increases in in vitro AFV activity in response to supply of substrates. Low level AFV activity was also detected from oilseed rape roots inoculated with B. subtilis. Gas chromatography mass spectrometry headspace analysis of B. subtilis cultures grown on various substrates revealed common similarities between substrates promoting AFV activity, although it was not possible to isolate individual antifungal compounds.

Antifungal Agents↗

Volatile compounds of Soumbala, a fermented African locust bean (Parkia biglobosa) food condiment.

AIMS: To determine the profile of volatile compounds responsible for the aroma of Soumbala produced spontaneously and with pure and mixed cultures of Bacillus subtilis and Bacillus pumilus. METHODS AND RESULTS: Traditional and controlled fermentation trials of African locust bean with pure and mixed starter cultures of B. subtilis (B7, B9 and B15) and B. pumilus (B10) were performed. Aroma volatiles were analysed using Likens-Nikerson method coupled with gas chromatography and mass spectrophotometry. Sensory analysis of Soumbala as well as rice dishes prepared with each type of Soumbala were carried out by 10 panellists. In total 116 compounds were identified. They included pyrazines, aldehydes, ketones, esters, alcohols, acids, alkanes, alkenes, amines, pyridines, benzenes, phenols, sulphurs, furans and other compounds. Using principal component analysis for comparison, the aroma profiles of the Soumbala samples could be separated into three groups. The sensory evaluation showed variable acceptability. However, it was noticed that Soumbala samples produced with starter cultures were scored higher than traditionally prepared Soumbala. CONCLUSIONS: Aroma volatiles and organoleptic properties of Soumbala vary according to the Bacillus isolates involved in the fermentation. SIGNIFICANCE AND IMPACT OF THE STUDY: This study contributes to the selection of Bacillus starter cultures for controlled production of Soumbala.

Bacillus↗

The capacity of subgingival microbiotas to produce volatile sulfur compounds in human serum.

Hydrogen sulfide is formed by the subgingival microbiotas of periodontal pockets. The capacity of these microbiotas to form various volatile sulfur compounds in human serum was studied. Bacterial samples from nine deep periodontal pockets were incubated for 7 days in human serum and the amounts of volatile sulfur compounds and the degradation of serum proteins were determined. Hydrogen sulfide was the predominant volatile sulfur compound, but also methyl mercaptan was formed in significant amounts. Only traces of dimethyl sulfide and dimethyl disulfide were detected. There was an extensive degradation of the serum proteins. In most of the reaction mixtures hydrogen sulfide reached highly toxic levels.

Bacteria↗

Protective effects of volatile agents against acetylcholine-induced bronchoconstriction in isolated perfused rat lungs.

BACKGROUND: Bronchoactive properties of volatile agents against lung constriction are well established. The purpose of this study was to investigate the ability of halothane (Hal), isoflurane (Iso), sevoflurane (Sev) and desflurane (Des) to alter the lung mechanics in the absence of an airway tone and during acetylcholine (Ach)-induced bronchoconstriction. METHODS: Low-frequency pulmonary impedance data (ZL) were collected from isolated, normo-perfused rat lungs under baseline conditions and following the injection of Ach (0.1 mg/kg) into the pulmonary artery. Measurements were performed without the administration of any anaesthetic agent in the first phase of the experiments and during inhalation without any volatile agent (control group, n = 6) or during inhalation of Hal (n = 6), Iso (n = 9), Sev (n = 6) or Des (n = 8) at 1 minimum alveolar concentration (MAC). The airway resistance (Raw) and parenchymal damping and elastance were estimated from the Z(L) data by model fitting. RESULTS: Under baseline conditions, the basic value of Raw was significantly decreased by Des (- 31.2 +/- 3.8%) and Sev (- 18.0 +/- 4.5%) administration, whereas Hal and Iso did not have a statistically significant effect on Raw (- 3.3 +/- 5.1% and - 8.6 +/- 2.4%, respectively). Moreover, all four inhalation anaesthetics prevented the increase in Raw following Ach administration, the findings ranging between - 14.3 +/- 11.4% for Hal and - 37.5 +/- 10.9% for Sev. CONCLUSIONS: Our results on a denervated isolated perfused lung model demonstrate the potential of Des and Sev to decrease the basal airway tone, whereas Iso and Hal are ineffective in this regard. All of these volatile agents markedly protect against Ach-induced bronchoconstriction.

Acetylcholine↗