Anesthetics, Local ; chemistry ; pharmacology ; toxicity ; Central Nervous System ; drug effects ; Ethyl Chloride ; chemistry ; pharmacology ; toxicity ; Humans ; Inhalation ; Male ; Medical History Taking ; Neurologic Examination ; Patient Care Management ; methods ; Psychotropic Drugs ; chemistry ; pharmacology ; toxicity ; Substance-Related Disorders ; etiology ; physiopathology ; psychology ; therapy ; Treatment Outcome ; Volatilization ; Young Adult

The safety of occupational exposure to inhaled anesthetics remains a concern among the medical staff in hospitals. Few reports are seen about the impact of inhaled anesthetics on the reproductive system, particularly that of males. Several clinical and basic studies on isoflurane and others suggest that inhaled anesthetics affect the reproductive system of rodents by decreasing the sperm count, inducing sperm morphological abnormality, reducing sperm motility, and changing the levels of reproductive hormones, the underlying mechanisms of which are mainly associated with the alteration of the hypothalamic-pituitary-gonadal axis and DNA damage and apoptosis of reproductive cells. This article reviews the main impacts of inhaled anesthetics on the male reproductive system and the possible mechanisms.
Anesthetics, Inhalation ; pharmacology ; Apoptosis ; DNA Damage ; Genitalia, Male ; drug effects ; Humans ; Isoflurane ; pharmacology ; Male ; Occupational Exposure ; Sperm Count ; Sperm Motility ; drug effects ; Spermatozoa ; drug effects

Anesthetics, Inhalation ; pharmacology ; Child ; Electrocardiography ; Heart Rate ; drug effects ; Humans ; Isoflurane ; analogs & derivatives ; pharmacology ; Methyl Ethers ; pharmacology

OBJECTIVEAnesthetic isoflurane plus surgery has been reported to induce cognitive impairment. The underlying mechanism and targeted intervention remain largely to be determined. Ginsenoside Rb1 was reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rb1 can attenuate isoflurane/surgery-induced cognitive dysfunction via inhibiting neuroinflammation and oxidative stress.

METHODSFive-months-old C57BL/6J female mice were treated with 1.4% isoflurane plus abdominal surgery for two hours. Sixty mg/kg ginsenoside Rb1 were given intraperitoneally from 7 days before surgery. Cognition of the mice were assessed by Barnes Maze. Levels of postsynaptic density-95 and synaptophysin in mice hippocampus were measured by Western blot. Levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in mice hippocampus were measured by ELISA.

RESULTSHere we show for the first time that the ginsenoside Rb1 treatment attenuated the isoflurane/surgery-induced cognitive impairment. Moreover, ginsenoside Rb1 attenuated the isoflurane/surgery-induced synapse dysfunction. Finally, ginsenoside Rb1 mitigated the isoflurane/surgery-induced elevation levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in the mice hippocampus.

CONCLUSIONThese results suggest that ginsenoside Rb1 may attenuate the isoflurane/surgery-induced cognitive impairment by inhibiting neuroinflammation and oxidative stress pending future studies.

Anesthetics, Inhalation ; adverse effects ; Animals ; Cognition ; Cognitive Dysfunction ; etiology ; prevention & control ; Female ; Ginsenosides ; pharmacology ; Hippocampus ; drug effects ; Inflammation ; etiology ; prevention & control ; Isoflurane ; adverse effects ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Postoperative Complications ; etiology ; prevention & control ; Random Allocation ; Surgical Procedures, Operative ; adverse effects ; Synapses ; metabolism

PURPOSE: Mentally disabled patients show different recovery profiles compared to normal patients after general anesthesia. However, the relationship of dose-recovery profiles of mentally disabled patients has never been compared to that of normal patients. MATERIALS AND METHODS: Twenty patients (10 mentally disabled patients and 10 mentally intact patients) scheduled to dental surgery under general anesthesia was recruited. Sevoflurane was administered to maintain anesthesia during dental treatment. At the end of the surgery, sevoflurane was discontinued. End-tidal sevoflurane and recovery of consciousness (ROC) were recorded after sevoflurane discontinuation. The pharmacodynamic relation between the probability of ROC and end-tidal sevoflurane concentration was analyzed using NONMEM software (version VII). RESULTS: End-tidal sevoflurane concentration associated with 50% probability of ROC (C50) and gamma value were lower in the mentally disabled patients (C50=0.37 vol %, gamma=16.5 in mentally intact patients, C50=0.19 vol %, gamma=4.58 in mentally disabled patients). Mentality was a significant covariate of C50 for ROC and gamma value to pharmacodynamic model. CONCLUSION: A sigmoid Emanx model explains the pharmacodynamic relationship between end-tidal sevoflurane concentration and ROC. Mentally disabled patients may recover slower from anesthesia at lower sevoflurane concentration at ROC an compared to normal patients.
*Anesthesia Recovery Period ; Anesthesia, Dental/*methods ; Anesthesia, General/*methods ; Anesthetics, Inhalation/*administration & dosage/pharmacology ; Case-Control Studies ; Child ; Child, Preschool ; Consciousness/drug effects ; Dental Care for Disabled/*methods ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Mentally Disabled Persons ; Methyl Ethers/*administration & dosage/pharmacology

PURPOSE: This study aims to investigate the most appropriate effect-site concentration of remifentanil to minimize cardiovascular changes during inhalation of high concentration desflurane. MATERIALS AND METHODS: Sixty-nine American Society of Anesthesiologists physical status class I patients aged 20-65 years were randomly allocated into one of three groups. Anesthesia was induced with etomidate and rocuronium. Remifentanil was infused at effect-site concentrations of 2, 4 and 6 ng/mL in groups R2, R4 and R6, respectively. After target concentrations of remifentanil were reached, desflurane was inhaled to maintain the end-tidal concentration of 1.7 minimum alveolar concentrations for 5 minutes (over-pressure paradigm). The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and end-tidal concentration of desflurane were measured for 5 minutes. RESULTS: The end-tidal concentration of desflurane increased similarly in all groups. The SBP, DBP, MAP and HR within group R4 were not significantly different as compared with baseline values. However, measured parameters within group R2 increased significantly 1-3 minutes after desflurane inhalation. The MAP within group R6 decreased significantly at 1, 2, 4, and 5 minutes (p<0.05). There were significant differences in SBP, DBP, MAP and HR among the three groups 1-3 minutes after inhalation (p<0.05). The incidence of side effects such as hyper- or hypo-tension, and tachy- or brady-cardia in group R4 was 4.8% compared with 21.8% in group R2 and 15.0% in group R6. CONCLUSION: The most appropriate effect-site concentration of remifentanil for blunting hemodynamic responses by inhalation of high concentration desflurane is 4 ng/mL.
Adult ; Aged ; Androstanols/adverse effects/pharmacology ; Anesthetics/adverse effects/pharmacology ; Anesthetics, Inhalation/adverse effects/*pharmacology ; Blood Pressure/drug effects ; Etomidate/adverse effects/pharmacology ; Female ; Heart/*drug effects ; Heart Rate/drug effects ; Humans ; Isoflurane/adverse effects/*analogs & derivatives/pharmacology ; Male ; Middle Aged ; Piperidines/adverse effects/*therapeutic use ; Protective Agents/adverse effects/*therapeutic use

PURPOSE: Despite the fact that desflurane prolongs the QTC interval in humans, little is known about the mechanisms that underlie these actions. We investigated the effects of desflurane on action potential (AP) duration and underlying electrophysiological mechanisms in rat ventricular myocytes. MATERIALS AND METHODS: Rat ventricular myocytes were enzymatically isolated and studied at room temperature. AP was measured using a current clamp technique. The effects of 6% (0.78 mM) and 12% (1.23 mM) desflurane on transient outward K+ current (I(to)), sustained outward current (I(sus)), inward rectifier K+ current (I(KI)), and L-type Ca2+ current were determined using a whole cell voltage clamp. RESULTS: Desflurane prolonged AP duration, while the amplitude and resting membrane potential remained unchanged. Desflurane at 0.78 mM and 1.23 mM significantly reduced the peak I(to) by 20+/-8% and 32+/-7%, respectively, at +60 mV. Desflurane (1.23 mM) shifted the steady-state inactivation curve in a hyperpolarizing direction and accelerated inactivation of the current. While desflurane (1.23 mM) had no effects on I(sus) and I(KI), it reduced the L-type Ca2+ current by 40+/-6% (p<0.05). CONCLUSION: Clinically relevant concentrations of desflurane appear to prolong AP duration by suppressing Ito in rat ventricular myocytes.
Action Potentials/*drug effects ; Anesthetics, Inhalation/*pharmacology ; Animals ; Calcium Channels, L-Type/physiology ; Heart Conduction System/drug effects/physiology ; Heart Ventricles/drug effects ; Isoflurane/*analogs & derivatives/pharmacology ; Myocardial Contraction/*drug effects/physiology ; Myocytes, Cardiac/*drug effects/physiology ; Patch-Clamp Techniques ; Potassium Channels/physiology ; Rats ; Rats, Sprague-Dawley

BACKGROUNDVolatile anesthetics (VAs) may affect varied and complex physiology processes by manipulating Ca(2+)-calmodulin (CaM). However, the detailed mechanism about the action of VAs on CaM has not been elucidated. This study was undertaken to examine the effects of VAs on the conformational change, hydrophobic site, and downstream signaling pathway of CaM, to explore the possible mechanism of anesthetic action of VAs.

METHODSReal-time second-harmonic generation (SHG) was performed to monitor the conformational change of CaM in the presence of VAs, each plus 100 µmol/L Ca(2+). A hydrophobic fluorescence indicator, 8-anilinonaphthalene-1-sulfonate (ANS), was utilized to define whether the VAs would interact with CaM at the hydrophobic site or not. High-performance liquid chromatography (HPLC) was carried out to analyze the activity of CaM-dependent phosphodiesterase (PDE1) in the presence of VAs. The VAs studied were ether, enflurane, isoflurane, and sevoflurane, with their aqueous concentrations 7.6, 9.5, 11.4 mmol/L; 0.42, 0.52, 0.62 mmol/L; 0.25, 0.31, 0.37 mmol/L and 0.47, 0.59, 0.71 mmol/L respectively, each were equivalent to their 0.8, 1.0 and 1.2 concentration for 50% of maximal effect (EC50) for general anesthesia.

RESULTSThe second-harmonic radiation of CaM in the presence of Ca(2+) was largely inhibited by the VAs. The fluorescence intensity of ANS, generated by binding of Ca(2+) to CaM, was reversed by the VAs. HPLC results also showed that AMP, the product of the hydrolysis of cAMP by CaM-dependent PDE1, was reduced by the VAs.

CONCLUSIONSOur findings demonstrate that the above VAs interact with the hydrophobic core of Ca(2+)-CaM and the interaction results in the inhibition of the conformational change and activity of CaM. This in vitro study may provide us insight into the possible mechanism of anesthetic action of VAs in vivo.

Adenosine Monophosphate ; analysis ; Anesthetics, Inhalation ; pharmacology ; Anilino Naphthalenesulfonates ; Calmodulin ; antagonists & inhibitors ; chemistry ; physiology ; Cyclic Nucleotide Phosphodiesterases, Type 1 ; analysis ; Fluorescence ; Humans ; Hydrophobic and Hydrophilic Interactions

OBJECTIVETo investigate whether inhaled sevoflurane is capable of producing delayed cardioprotection effect in rats and its underlying mechanisms.

METHODSMale Sprague-Dawley rats inhaled 1.0 minimum alveolar concentration (MAC) sevoflurane, 1.5 MAC sevoflurane,or O(2) for 1 h. After 24 h and 48 h the left coronary artery of rats was occluded for 30 min,followed by 120 min of reperfusion. Hemodynamics was continuously recorded and myocardial infarct size was determined by Evans blue and triphenyltetrazolium chloride staining. The expression of nitric oxide synthase (NOS) was assessed by immunoblotting.

RESULTS1.0 MAC sevoflurane and 1.5 MAC sevoflurane improved cardiac pump function after reperfusion and reduced myocardial infarct size with the increased iNOS expression (P<0.05). However,the expression of eNOS and p-eNOS was not affected (P>0.05). A selective iNOS inhibitor 1400 W abolished the cardioprotection effect induced by inhalation of 1.0 MAC sevoflurane for 24 h.

CONCLUSIONSevoflurane produces delayed cardioprotection through the up-regulation of iNOS expression.

Anesthetics, Inhalation ; pharmacology ; Animals ; Disease Models, Animal ; Ischemic Preconditioning, Myocardial ; Male ; Methyl Ethers ; pharmacology ; Myocardial Reperfusion Injury ; enzymology ; pathology ; prevention & control ; Myocardium ; enzymology ; pathology ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Sprague-Dawley ; Up-Regulation ; drug effects

The term "burst-suppression" is used to describe the electroencephalogram (EEG) pattern characterized by theta or delta waves, at times intermixed with faster waves, and intervening periods of relative quiescence. Burst-suppression pattern can reflect the seriously suppressed brain activity under deep anesthesia. To investigate the relationship between burst-suppression features and anesthetic concentration, we adopted four straightforward indexes, i. e., burst-suppression ratio (BSR), burst frequency, burst amplitude and suppression amplitude, and used them to analyze the EEG recordings in ten isoflurane-anesthetized rats. It was found that all the four burst-suppression indexes changed along with anesthetic concentration, that BSR and burst amplitude increased with higher concentration of isoflurane while burst frequency and suppression amplitude decreased, and that BSR was the most sensitive and consistent measurement to indicate isoflurane concentration so it constituted a valuable tool for timely evaluation of burst-suppression feature under deep anesthesia. The result also showed that the composition of carrier gas (i. e. pure oxygen vs. mixed oxygen) did not influence the effect of anesthesia significantly; and the four indexes of burst-suppression features could keep relatively stable within 60 min under the isoflurane concentration of 2%. The present study provides quantitative information of burst-suppression features under different anesthetic depth and may help to develop a clinically satisfied system that could quantify the characteristics of EEG and rigorously evaluate the cerebral state of patients.
Anesthesia, Inhalation ; Anesthetics, Inhalation ; pharmacology ; Animals ; Brain ; metabolism ; Electroencephalography ; drug effects ; Isoflurane ; pharmacology ; Male ; Rats ; Rats, Wistar ; Signal Processing, Computer-Assisted