Desflurane Inhalation Research Articles

The effect of intravenous labetalol administration on hemodynamic responses during desflurane inhalation.

BackgroundInspired concentrations of desflurane ≥ 1 minimum alveolar anesthetic concentration (MAC) have been related to sympathetic stimulation such as hypertension and tachycardia. The current study examined whether labetalol, an α1 and β-adrenergic antagonist would blunt these hemodynamic responses.MethodsFifty-four ASA physical status I patients, aged 20-60 years, were enrolled in this study. The patients were randomly divided into 2 groups. The breathing circuit was primed with an end-tidal desflurane concentration of 1.2 MAC in 6 L/min O2. Normal saline 5 ml or labetalol 0.3 mg/kg was injected into groups S and L respectively. After 5 minutes, anesthesia was induced with intravenous etomidate 0.2 mg/kg and vecuronium 0.1 mg/kg. Each patient inhaled desflurane through a tight fitting facemask. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and end-tidal concentration of desflurane (et-des) were measured at 5 minutes after saline or labetalol injection (baseline) and every 1 minute for 5 minutes after desflurane inhalation and for 2 minutes after intubation.ResultsIn the saline injection group (group S), desflurane inhalation increased heart rate and blood pressure, while labetalol 0.3 mg/kg attenuated the heart rate and blood pressure increase in group L. After tracheal intubation, heart rate and blood pressure were significantly lower in group L than in group S.ConclusionsThese results demonstrate that administration of intravenous labetalol is effective in attenuating tracheal intubation and desflurane-induced hemodynamic responses.

The median effective effect-site concentration of remifentanil for minimizing the cardiovascular changes to endotracheal intubation during desflurane anesthesia in pediatric patients

BackgroundDesflurane has the most rapid onset and offset of action among the volatile anesthetic agents used for general anesthesia, but it can cause airway reactivity, tachycardia, and hypertension during induction, especially in pediatric patients. This study was designed to determine a median effective effect-site concentration (EC50) of remifentanil to prevent the cardiovascular changes due to tracheal intubation during the 1 minimum alveolar concentration (MAC) desflurane inhalation, which was required to prevent movement in response to a noxious stimulus in 50% of subjects, in pediatric patients.MethodsTwenty-four pediatric patients between the ages 5-15 years were enrolled in this study. We injected thiopental intravenously, at the same time remifentanil was infused by Target Controlled Infusion (TCI) device. When the target effect-site concentration (Ce) of remifentanil reached a preset level, desflurane was administrated through the facial mask. Then, we assessed the signs of desflurane related airway reactivity and cardiovascular changes for 2 min. The up-and-down criteria was a 20% change in systolic blood pressure (SBP) and a heart rate (HR) between just prior to intubation and 1 min after intubation. The EC50 of remifentanil was calculated from 8 independent pairs using Dixon's up-and-down method.ResultsWe studied 24 pediatric patients in range of 1-5 ng/ml of the Ce of remifentanil. No patient showed airway reactivity during the study. The EC50 of remifentanil to suppress the hemodynamic changes after tracheal intubation during desflurane anesthesia was calculated as 3.4 ± 0.9 ng/ml.ConclusionsIn pediatric anesthesia, the EC50 of remifentanil to minimize the cardiovascular changes due to tracheal intubation during 1 MAC desflurane anesthesia was 3.4 ± 0.9 ng/ml.

Optimal effect-site concentration of remifentanil for preventing development of hypertension during tracheal intubation with inhaled desflurane induction.

BackgroundThe aim of the present study was to determine the effect-site concentration of remifentanil needed to prevent haemodynamic instability during tracheal intubation with inhaled desflurane induction.MethodsOne hundred American Society of Anesthesiologists I and II female patients were randomized to receive an effect-site concentration of remifentanil of 0, 1, 2, 3, or 4 ng/ml. Induction of anaesthesia was started with intravenous injection of propofol 2 mg/kg. Ninety seconds after the completion of propofol injection, rocuronium (0.8 mg/kg) and remifentanil were administered simultaneously with 3% desflurane inhalation. Tracheal intubation was attempted 150 sec after the commencement of remifentanil administration.ResultsA probit model of remifentanil concentration was predictive of successful intubation without development of hypertension (P for goodness-of-fit = 0.419). The effect-site concentration of remifentanil needed to achieve successful intubation without development of hypertension in 95% of the patients was 3.3 ng/ml (95% confidence interval, 2.6-4.8 ng/ml).ConclusionsThe effect-site concentration of remifentanil of 3.3 ng/ml is effective in blunting the haemodynamic response in 95% of the patients when 2.0 mg/kg of propofol induction was followed by 3% desflurane inhalation.

The target concentration of remifentanil to suppress the hemodynamic response to endotracheal intubation during inhalational induction with desflurane

BackgroundAnesthesia induction with desflurane is troublesome because of the frequent sympathetic hyperactivity during desflurane administration. We thought that a low concentration of desflurane combined with a target-controlled infusion (TCI) of remifentanil would eliminate the desflurane-related complications and provide hemodynamic stability during desflurane induction. An up-and-down study was planned to find the target effect-site concentration of remifentanil to block the hemodynamic response to endotracheal intubation, the highest level of stimulus, during anesthesia induction with administering desflurane at 1 MAC.MethodsRemifentanil TCI was initiated before desflurane administration. When the preset target was achieved, spontaneous inhalation of desflurane 1 MAC was performed until the patients became unconscious. Laryngoscopic tracheal intubation was facilitated with rocuronium injection. The starting concentration of remifentanil and the test space were 5 and 1 ng/ml, respectively. The criteria for up-and-down was a 20% increase of the mean arterial pressure or heart rate after intubation. The median effective concentration (EC50) of remifentanil was calculated from 6 independent pairs. The complications related with remifentanil and desflurane were assessed during the study.ResultsWe studied 20 patients using 2-5 ng/ml of the effect-site concentrations of remifentanil. The EC50 of remifentanil was 3.7 ng/ml. Loss of consciousness was achieved at 125 ± 22 s after desflurane inhalation and this was irrespective of the combined remifentanil concentrations. Any remifentanil-related complication was not observed. Transient cough was seen in one patient who received 2 ng/ml of remifentanil.ConclusionsWe demonstrated that uncomplicated induction with desflurane was possible by the use of target-controlled remifentanil. The EC50 of remifentanil to block the hemodynamic response to tracheal intubation was 3.7 ng/ml during inhalational induction with 1 MAC desflurane.

A Randomized Comparison of Target-Controlled Infusion of Remifentanil and Propofol with Desflurane and Fentanyl for Laryngeal Surgery

Aims: To compare the clinical profile of target-controlled infusion (TCI) of remifentanil (REM) + propofol (PRO) with fentanyl (FEN) bolus infusion with desflurane (DES) inhalation in direct laryngoscopic surgery. Methods: Sixty patients who were scheduled to undergo laryngoscopic surgery were randomly assigned to two groups (n = 30, respectively). One group of patients received a TCI of REM + PRO anesthetic treatment, while the patients in the other group received a bolus infusion of FEN and DES inhalation treatment. The hemodynamics, recovery profiles and unexpected events that occurred in both groups were recorded. Results: The hemodynamics of the patients in the TCI group was more stable during tracheal intubation, direct laryngoscope insertion and extubation. The mean arterial pressure was also significantly lower in the TCI group compared with the FEN/DES group. The TCI group also showed faster recovery profiles (e.g. a shorter time needed for response to verbal commands, autonomous breathing, tracheal extubation and orientation recovery). The FEN/DES group had lower Stewart recovery scores during the first 15 min determined at the postanesthesia care unit. However, there were no significant differences regarding the occurrence of unexpected events and postoperative complications between the two groups. Conclusions: TCI of REM + PRO anesthesia appears to be a reasonable alternative to FEN bolus infusion combined with DES inhalation during direct laryngoscopic surgery.

Cardiac arrest induced by submucosal injection of epinephrine in a patient with variant angina

This case report describes a 35-year old male who experienced ventricular tachycardia induced by intramucosal injection of epinephrine (1:100,000). Under general anaesthesia with desflurane inhalation, 1.5% lidocaine containing 1:100,000 epinephrine was injected into the nasal mucosa for septoplasty. ST segment elevation and QRS widening occurred after 10 minutes and progressed to pulseless ventricular tachycardia. A sinus rhythm was restored after cardiopulmonary resuscitation with electrical cardioversion. The cardiac enzymes were significantly elevated after the event. Exercise-stress testing and coronary angiography were normal. However, an injection of acetylcholine into the coronary artery provoked vasospasm in the left anterior descending and circumflex arteries. This case illustrates an unusual response to low dose epinephrine with cardiac arrest induced in a patient with undiagnosed variant angina.

Blockade of anaesthetic-induced preconditioning in the hyperglycaemic myocardium: The regulation of different mitogen-activated protein kinases

Preconditioning by volatile anaesthetics is blocked by hyperglycaemia. The regulation of mitogen-activated protein kinases during this effect has yet not been investigated. For infarct size measurements, anaesthetized rats were subjected to 25 min coronary artery occlusion followed by 120 min reperfusion. Control animals were not further treated. One group was preconditioned by two 5-min periods of desflurane inhalation (desflurane preconditioning, Des-preconditioning, 1MAC), each followed by 10-min washout. Four groups received glucose 50% in order to achieve blood glucose concentrations between 22.2 and 33.3 mM/l. Glucose infusion started 40 min before ischaemia (early hyperglycaemia, EH) and stopped with the onset of artery occlusion with (EH+Des-preconditioning) or without (EH) preconditioning. The other two groups received glucose during ischaemia (late hyperglycaemia, LH), again with (LH+Des-preconditioning) or without (LH) preconditioning. Additional hearts were excised for Western blot of mitogen-activated protein kinases. Infarct size was reduced from 51.7 ± 9.0% in controls to 28.8 ± 11.8% after Des-preconditioning ( P< 0.01 vs Con). Hyperglycaemia alone did not affect infarct size (EH, 51.5 ± 9.0%, LH, 44.3 ± 16.9%), but EH as well as LH blocked Des-preconditioning (49.1 ± 12.3%, P< 0.01, 48.1 ± 17.6%, P< 0.05 vs Des-preconditioning). All three mitogen-activated protein kinases showed a similar time course pattern of phosphorylation in the Des-preconditioning, EH and EH+Des-preconditioning group. Despite the lack of cardioprotection, mitogen-activated protein kinases are activated in hyperglycaemic myocardium. Therefore, it can be assumed that the hyperglycaemic induced blockade of Des-preconditioning is situated downstream or in parallel of these mitogen-activated protein kinases or involves different signal transduction pathways.

The effect of continuous remifentanil infusion on airway reactivity during desflurane inhalation

The effect of continuous remifentanil infusion on airway reactivity during desflurane inhalation

Desflurane but Not Sevoflurane Impairs Airway and Respiratory Tissue Mechanics in Children with Susceptible Airways

Although sevoflurane and desflurane exert bronchoactive effects, their impact on the airway and respiratory tissue mechanics have not been systematically compared in children, especially in those with airway susceptibility (AS). The aim of this study was to assess airway and respiratory tissue mechanics in children with and without AS during sevoflurane and desflurane anesthesia. Respiratory system impedance was measured in healthy control children (group C, n = 20) and in those with AS (group AS, n = 20). Respiratory system impedance was determined during propofol anesthesia and during inhalation of sevoflurane and desflurane 1 minimum alveolar concentration in random order. Airway resistance, tissue damping, and elastance were determined from the respiratory system impedance spectra by model fitting. Children in group AS exhibited significantly higher respiratory impedance parameters compared with those in group C. Sevoflurane slightly decreased airway resistance (-7.0 +/- 1.5% vs. -4.8 +/- 2.4% in groups C and AS, respectively) in both groups. In contrast, desflurane caused elevations in airway resistance and tissue mechanical parameters, with markedly enhanced airway narrowing in children with AS (18.2 +/- 2.8% vs. 53.9 +/- 5%; P < 0.001 for airway resistance in groups C and AS, respectively). Neither the order of drug administration nor the time after the establishment of their steady state concentrations affected these findings. These results emphasized the deleterious effects of desflurane on the airways, particularly in children with susceptible airways in contrast with the consistent beneficial effects of sevoflurane, questioning the use of desflurane in children with AS.

The Effect of Continuous Remifentanil Infusion on the Airway Reactivity during Desflurane Inhalation

Background: Because desflurane can cause airway reactivity, the use of opioids are aimed at its reduction. This study was designed to evaluate the effect of continuous remifentanil infusion on the airway reactivity during desflurane inhalation. Methods: 108 adult ASA physical status class I patients were enrolled in this study. The patients were divided into four groups.The breathing circuit was primed with 8 vol% desflurane in 3 L/min each of N2O and O2. Anesthesia was induced with 0.2 mg/kg of intravenous etomidate. After 2 minutes, either 20 ml/hr saline, or 0.15, 0.25 or 0.35μg/kg/min remifentanil, groups S, R1, R2 and R3, respectively, was infused. Each patient inhaled the gas mixture through a tight fitting facemask. During this period, the coughing, secretions, breathing hold, laryngospasms, excitatory movements and hemodynamics were measured. Results: The coughing, spasms, secretions and excitatory movements were significantly lower in the remifentanil than the saline infusion group (P ＜ 0.05). However, the breathing hold was significantly higher in group R3 (P ＜ 0.001). The mean arterial pressure and heart rate were more stable in groups R1 and R2. Conclusions: These results demonstrate that groups R1 and R2 had significantly reduced airway reactivity, with stabilize hemodynamics, during desflurane inhalation.

Desflurane-induced Preconditioning against Myocardial Infarction Is Mediated by Nitric Oxide

Volatile anesthetics induce myocardial preconditioning through a signal transduction pathway that is remarkably similar to that observed during ischemic preconditioning. Nitric oxide-dependent signaling plays an important role in anesthetic and ischemic preconditioning. Therefore, the authors tested the hypothesis that desflurane-induced preconditioning is mediated by nitric oxide. Barbiturate-anesthetized rabbits were instrumented for measurement of hemodynamics. All rabbits were subjected to 30-min coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size was assessed with triphenyltetrazolium chloride staining. Myocardial nitric oxide synthase activity was assessed with a [H]L-arginine-conversion assay. Rabbits were randomized to five separate experimental groups. They received 0.0 or 1.0 minimum alveolar concentration desflurane for 30 min, which was discontinued 30 min before ischemia in the absence or presence of the nitric oxide synthase inhibitor N-nitro-L-arginine (L-NA). L-NA was given either 20 min before or 10 min after desflurane administration, respectively. Data are mean +/- SEM. Infarct size was 56 +/- 8% in control experiments. Desflurane significantly (P < 0.05) reduced infarct size to 35 +/- 4%. Preconditioning by desflurane was totally blocked by administration of L-NA either during or after desflurane inhalation (58 +/- 4 and 59 +/- 9%, respectively). L-NA alone had no effect on infarct size (56 +/- 7%). Nitric oxide synthase activity was significantly (P < 0.05) increased by desflurane. The results demonstrate that desflurane-induced preconditioning markedly reduced myocardial infarct size. This beneficial effect was blocked by the nitric oxide synthase inhibitor L-NA either during or after desflurane-administration. These data suggest that early desflurane-induced preconditioning is mediated by nitric oxide.

Desflurane differentially affects the release of proinflammatory cytokines in plasma and bronchoalveolar fluid of endotoxemic rats

Previous studies have indicated that volatile anaesthetics can attenuate the inflammatory response to lipopolysaccharide (LPS) and other proinflammatory stimuli in vitro and in vivo. Thus far, no studies are available on the influences of desflurane on the cytokine-release. We therefore aimed to investigate the effects of desflurane on the systemic and pulmonary release of proinflammatory cytokines in endotoxemic rats. Eighteen anaesthetized and ventilated Sprague-Dawley rats were randomly assigned to the following groups: LPS-only: Six animals received LPS (5 mg/kg, i.v.) with no further intervention. LPS-Desflurane: Six animals received continuous inhalation of 1MAC Desflurane before and during endotoxemia with LPS (5 mg/kg, i.v.). Sham: Six animals served as control without inhalation of desflurane and endotoxemia. After 4 h, levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in plasma and bronchoalveolar fluid were analyzed. Nitrite production as a readout for nitric oxide (NO) release from alveolar macrophages was measured by Griess assay. IkappaB-alpha degradation and iNOS-protein in macrophage homogenates were determined by Western Blotting. Inhalation of desflurane during endotoxemia showed a significant decrease in release of the proinflammatory cytokines TNF-alpha (-61%, P< or =0.05) and IL-1beta (-47%, P< or =0.05) in plasma as compared to LPS-only group, whereas the release of IL-6 was not significantly affected by desflurane. Within the lung, the NO-release was notably increased in supernatants of cultured alveolar macrophages from desflurane-group compared to both LPS-only and Sham group. IkappaB-alpha degradation in alveolar macrophages was impaired in the Desflurane-group as compared to the LPS-only group. Our data implicate that inhalation of 1MAC Desflurane during experimental endotoxemia differentially affects the inflammatory response in rats.

Comparison of the Effects on Increase of Heart Rate and Blood Pressure between Tracheal Intubation and Desflurane Inhalation during Propofol Anesthesia

Background: This study was undertaken to compare the hemodynamic effects between desflurane inhalation and endotracheal intubation, and to evaluate the intensity of airway irritation by desflurane inhalation of high concentration. Methods: Twenty adult patients with ASA 1 were enrolled in this study. Radial artery was catheterized and heart rate (HR) and mean arterial pressure (MAP) were measured throughout the study. Anesthesia was induced by propofol and effect site concentration of propofol was maintained at 4/ml using target controlled infusor (TCI). Peak HR and MAP following tracheal intubation were recorded and inhalation of 12 vol% desflurane was started after HR and MAP had been returned to pre-intubation value. The HR, MAP, inspiratory (Fi) and end-tidal fraction (Et) were observed after desflurane inhalation for 10 minutes. Results: The HR and MAP were significantly increased after tracheal intubation and desflurane inhalation, and the peak hemodynamic change after desflurane inhalation was significantly delayed as compared to tracheal intubation. The maximal HR change from baseline after tracheal intubation or desflurane inhalation was not different, but maximal MAP change was significantly lower during desflurane inhalation compared with tracheal intubation. The maximal change of HR and MAP when end-tidal fraction of desflurane had been reached 6 vol% was lower than that of tracheal intubation or desflurane inhalation. Conclusions: Despite of propofol administration required for general anesthesia, the HR and MAP were significantly increased during desflurane inhalation of high concentration. In particular, the extent of HR increase during desflurane inhalation was similar to that by tracheal intubation.

Massive Inhalation of Desflurane due to Vaporizer Dysfunction

Massive Inhalation of Desflurane due to Vaporizer Dysfunction

Comparison of the effects of desflurane and sevoflurane on the QTc interval and QT dispersion

Objective — The effects of desflurane and sevoflurane on QT interval and QT dispersion have been investigated in a prospective, double-blind, randomized study of patients undergoing noncardiac surgery.Interventions — Sixty American Society of Anaesthesiologists physical status I-II adult patients were randomly assigned to two groups.Anaesthesia was induced with inhalation of desflurane (desflurane group) or sevoflurane (sevoflurane group) in increasing concentrations to 3 minimal alveolar concentration level. The maintenance of anaesthesia was provided with 2 minimal alveolar concentration agents in both groups until the end of the study. Electrocardiogram, heart rate and blood pressure were recorded as follows: before premedication, before induction, 1 and 3 min after the induction of anaesthesia, after the administration of vecuronium and after the tracheal intubation. The induction times and the complications were recorded.Measurements and results — The QTc interval was significantly more prolonged with desflurane than with sevoflurane at the first and third minute after the induction, and at the third minute after the administration of vecuronium.There were no significant differences in the QT dispersion between the two groups. Heart rate and blood pressure were found to be significantly higher in the desflurane group.Conclusion — The QTc interval was more prolonged with desflurane than sevoflurane, and QT dispersion was normal with both agents.

Laryngeal mask airway can be inserted with inhaled desflurane induction

In this prospective, randomized, controlled trial, we investigated the reliability of laryngeal mask airway (LMA) insertion with inhaled desflurane. Eighty patients undergoing elective surgery were randomized into two groups to receive either 2.5 mg x kg(-1) propofol (n = 40) or tidal breath desflurane (n = 40) induction followed by LMA insertion. All patients received fentanyl 1 microg x kg(-1) 2 min before induction. Inhalation of desflurane was started at 3% and increased by 3% every 3-5 breaths up to settings of 12%. Insertion of the LMA was faster in the propofol group (131.8 s versus 228.6 s, P < 0.01). The number of patients in whom the jaw opening was described as good (95% versus 72.5%, P = 0.27, for the desflurane and propofol groups, respectively) and the ease of LMA insertion described as good (87.5% versus 72.5%, P = 0.6) were comparable. The LMA was inserted in a single attempt in the majority of patients in both groups (80% versus 77.5%, P = 0.90). There were more complications at insertion in the propofol group than in the desflurane group (2.5% versus 19.5%, P < 0.01), especially for apnea (7.5% versus 70%, P < 0.01) and excitatory movements (2.5% versus 25%, P < 0.01). There were significant decreases in the mean arterial pressure in the propofol group compared to baseline data over the first 5 min of induction. Mean arterial pressure, heart rate, and S(p)(O2) remained stable during the same period in the desflurane group. We demonstrated that inhaled desflurane when used with caution in a controlled manner provided acceptable conditions for LMA insertion.

Effects of desflurane and mode of ventilation on cardiovascular and respiratory functions and clinicopathologic variables in horses

To quantitate the effects of desflurane and mode of ventilation on cardiovascular and respiratory functions and identify changes in selected clinicopathologic variables and serum fluoride values associated with desflurane anesthesia in horses. 6 healthy adult horses. Horses were anesthetized on 2 occasions: first, to determine the minimum alveolar concentration (MAC) of desflurane in O2 and second, to characterize cardiopulmonary and clinicopathologic responses to 1X, 1.5X, and 1.75X desflurane MAC during both controlled and spontaneous ventilation. Mean +/- SEM MAC of desflurane in horses was 8.06 +/- 0.41 %; inhalation of desflurane did not appear to cause airway irritation. During spontaneous ventilation, mean PaCO2 was 69 mm Hg. Arterial blood pressure, stroke volume, and cardiac output decreased as the dose of desflurane increased. Conditions of intermittent positive pressure ventilation and eucapnia resulted in further cardiovascular depression. Horses recovered quickly from anesthesia with little transient or no clinicopathologic evidence of adverse effects. Serum fluoride concentration before and after administration of desflurane was below the limit of detection of 0.05 ppm (2.63microM/L). Results indicate that desflurane, like other inhalation anesthetics, causes profound hypoventilation in horses. The magnitude of cardiovascular depression is related to dose and mode of ventilation; cardiovascular depression is less severe at doses of 1X to 1.5X MAC, compared with known effects of other inhalation anesthetics under similar conditions. Desflurane is not metabolized to an important degree and does not appear to prominently influence renal function or hepatic cellular integrity or function.

The Anesthetic Cascade

The Anesthetic Cascade

Comparison of Desflurane-induced Circulatory Responses by the Rate of Increase in Inhaled Desflurane Concentration

Background: A rapid increase in desflurane concentration induces tachycardia and hypertension and increases plasma catecholamine concentration. No clinical study is available as to whether the desflurane-induced circulatory responses is blunted by the rate of increase in inhaled desflurane concentration although there were many studies about methods to blunt the circulatory responses. The current study examined to compare desflurane-induced circulatory responses by the rate of increase in inhaled desflurane concentration. Methods: Unpremedicated sixty ASA physical status 1 patients, aged 20-60 years, scheduled for elective surgery under general anesthesia were randomly allocated into one of two groups. The inspired concentration of desflurane via mask was increased to 12.0 vol% abruptly (group 1), or during 120 seconds (group 2). The target was to produce an end-tidal concentration of desflurane (ETdesf) of 10.0 vol% which was maintained until the end of the study by adjusting the vaporizer setting, when necessary. Heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), systemic vascular resistance (SVR), ETdesf, end-tidal concentration of carbon dioxide, and peripheral oxygen saturation were measured at baseline and every 30 seconds for 5 minutes after inhalation of desflurane and for 2 minutes after intubation. Results: HR, blood pressure, and CI were significantly increased in two groups compared with baseline, but significant differences in maximum values were not observed between two groups. There were no significant differences between groups of the ETdesf at the maximal HR and MAP. Incidences of hypertension and tachycardia were lesser in slowly increased inhaled desflurane concentration (group 2) than abruptly increased group (group 1). Conclusions: The present study demonstrates that increasing inhaled desflurane concentration slowly for mask ventilation is partially effective in attenuating desflurane-induced circulatory responses.

Desflurane Preconditioning Induces Time-dependent Activation of Protein Kinase C Epsilon and Extracellular Signal-regulated Kinase 1 and 2 in the Rat Heart In Vivo

Activation of protein kinase C epsilon (PKC-epsilon) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) are important for cardioprotection by preconditioning. The present study investigated the time dependency of PKC-epsilon and ERK1/2 activation during desflurane-induced preconditioning in the rat heart. Anesthetized rats were subjected to regional myocardial ischemia and reperfusion, and infarct size was measured by triphenyltetrazoliumchloride staining (percentage of area at risk). In three groups, desflurane-induced preconditioning was induced by two 5-min periods of desflurane inhalation (1 minimal alveolar concentration), interspersed with two 10-min periods of washout. Three groups did not undergo desflurane-induced preconditioning. The rats received 0.9% saline, the PKC blocker calphostin C, or the ERK1/2 inhibitor PD98059 with or without desflurane preconditioning (each group, n = 7). Additional hearts were excised at four different time points with or without PKC or ERK1/2 blockade: without further treatment, after the first or the second period of desflurane-induced preconditioning, or at the end of the last washout phase (each time point, n = 4). Phosphorylated cytosolic PKC-epsilon and ERK1/2, and membrane translocation of PKC-epsilon were determined by Western blot analysis (average light intensity). Desflurane significantly reduced infarct size from 57.2 +/- 4.7% in controls to 35.2 +/- 16.7% (desflurane-induced preconditioning, mean +/- SD, P < 0.05). Both calphostin C and PD98059 abolished this effect (58.8 +/- 13.2% and 64.2 +/- 15.4% respectively, both P < 0.05 versus desflurane-induced preconditioning). Cytosolic phosphorylated PKC-epsilon reached its maximum after the second desflurane-induced preconditioning and returned to baseline after the last washout period. Both calphostin C and PD98059 inhibited PKC-epsilon activation. ERK1/2 phosphorylation reached its maximum after the first desflurane-induced preconditioning and returned to baseline after the last washout period. Calphostin C had no effect on ERK1/2 phosphorylation. Both, PKC and ERK1/2 mediate desflurane-induced preconditioning. PKC-epsilon and ERK1/2 are both activated in a time dependent manner during desflurane-induced preconditioning, but ERK1/2 activation during desflurane-induced preconditioning is not PKC dependent. Moreover, ERK1/2 blockade abolished PKC-epsilon activation, suggesting ERK-dependent activation of PKC-epsilon during desflurane-induced preconditioning.