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Introduced in the late 1950s, halothane became the anesthetic of choice for inhalational induction of children for over 40 years. Halothane enjoyed a generally favorable safety record during its time, but its cardiac contractility depressant effect—well tolerated by most age groups—was profoundly heightened in neonates and infants, leading to increased incidences of hypotension and cardiac arrest. The neonatal myocardium is immature and is characterized by poor ventricular compliance, poor contractility due to fewer contractile elements, immature sympathetic innervation with decreased norepinephrine stores, and immature mechanisms for storage and exchange of calcium in the sarcoplasmic reticulum. In vitro studies of myocardial contractility of mammalian fetal and adult myocardium demonstrated that the fetal heart was twice as sensitive to halothane as the adult. Clinical studies demonstrated that most neonates and infants less than 6 months of age experienced hypotension during halothane induction of anesthesia and significantly (p <.01) greater decreases in blood pressure than older children at equipotent concentrations of halothane. Intraoperative cardiac arrest during the halothane era occurred over twice as frequently in neonates aged less than 1 month than in infants aged 1–12 months and nearly 10 times more frequently than children 1–5 years of age. Halothane was associated with 66% of intraoperative drug‐related cardiac arrests in children. The halothane era began to close in the late 1990s with the introduction of sevoflurane, which had a more favorable hemodynamic profile. Shortly thereafter, halothane was completely displaced from pediatric anesthesia practice in North America. [ABSTRACT FROM AUTHOR]

Malignant hyperthermia susceptibility (MHS) is an autosomal dominant pharmacogenetic disorder that manifests as a hypermetabolic state when carriers are exposed to halogenated volatile anesthetics or depolarizing muscle relaxants. In animals, heat stress intolerance is also observed. MHS is linked to over 40 variants in RYR1 that are classified as pathogenic for diagnostic purposes. More recently, a few rare variants linked to the MHS phenotype have been reported in CACNA1S, which encodes the voltage-activated Ca2+ channel CaV1.1 that conformationally couples to RyR1 in skeletal muscle. Here, we describe a knock-in mouse line that expresses one of these putative variants, CaV1.1-R174W. Heterozygous (HET) and homozygous (HOM) CaV1.1-R174W mice survive to adulthood without overt phenotype but fail to trigger with fulminant malignant hyperthermia when exposed to halothane or moderate heat stress. All three genotypes (WT, HET, and HOM) express similar levels of CaV1.1 by quantitative PCR, Western blot, [3H]PN200-110 receptor binding and immobilization-resistant charge movement densities in flexor digitorum brevis fibers. Although HOM fibers have negligible CaV1.1 current amplitudes, HET fibers have similar amplitudes to WT, suggesting a preferential accumulation of the CaV1.1-WT protein at triad junctions in HET animals. Never-the-less both HET and HOM have slightly elevated resting free Ca2+ and Na+ measured with double barreled microelectrode in vastus lateralis that is disproportional to upregulation of transient receptor potential canonical (TRPC) 3 and TRPC6 in skeletal muscle. CaV1.1-R174W and upregulation of TRPC3/6 alone are insufficient to trigger fulminant malignant hyperthermia response to halothane and/or heat stress in HET and HOM mice.

In recent years, hydrofluorocarbon compounds such as chlorofluorocarbons, hydrochlorofluorocarbons, and 2‐bromo‐2‐chloro‐1,1,1‐trifluoroethane (halothane) have been used as fluorine‐containing building blocks to construct functional fluorine‐containing compounds, e. g., polymers, liquid crystals, and medicines. Hydrofluorocarbons promote the formation of reactive fluoroalkyl or fluoroalkenyl species via anionic or radical processes, and these species can act as nucleophiles or electrophiles depending on the reaction conditions. Progress in fluorine chemistry using hydrofluorocarbons in the last 30 years is described in this review and diverse reactions are discussed, including the fluoroalkyl/alkenyl products and proposed mechanisms involved. [ABSTRACT FROM AUTHOR]

As the number of radiotherapy and radiology diagnostic procedures increases from year to year, so does the use of general volatile anaesthesia (VA). Although considered safe, VA exposure can cause different adverse effects and, in combination with ionising radiation (IR), can also cause synergistic effects. However, little is known about DNA damage incurred by this combination at doses applied in a single radiotherapy treatment. To learn more about it, we assessed DNA damage and repair response in the liver tissue of Swiss albino male mice following exposure to isoflurane (I), sevoflurane (S), or halothane (H) alone or in combination with 1 or 2 Gy irradiation using the comet assay. Samples were taken immediately (0 h) and 2, 6, and 24 h after exposure. Compared to control, the highest DNA damage was found in mice receiving halothane alone or in combination with 1 or 2 Gy IR treatments. Sevoflurane and isoflurane displayed protective effects against 1 Gy IR, while with 2 Gy IR the first adverse effects appeared at 24 h post-exposure. Although VA effects depend on liver metabolism, the detection of unrepaired DNA damage 24 h after combined exposure with 2 Gy IR indicates that we need to look further into the combined effects of VA and IR on genome stability and include a longer time frame than 24 h for single exposure as well as repeated exposure as a more realistic scenario in radiotherapy treatment.

Introduction: Malignant Hyperthermia (MH) is a pharmacogenetic, hereditary and autosomal dominant syndrome triggered by halogenates/succinylcholine. The In Vitro Contracture Test (IVCT) is the gold standard diagnostic test for MH, and it evaluates abnormal skeletal muscle reactions of susceptible individuals (earlier/greater contracture) when exposed to caffeine/halothane. MH susceptibility episodes and IVCT seem to be related to individual features. Objective: To assess variables that correlate with IVCT in Brazilian patients referred for MH investigation due to a history of personal/family MH. Methods: We examined IVCTs of 80 patients investigated for MH between 2004‒2019. We recorded clinical data (age, sex, presence of muscle weakness or myopathy with muscle biopsy showing cores, genetic evaluation, IVCT result) and IVCT features (initial and final maximum contraction, caffeine/halothane concentration triggering contracture of 0.2g, contracture at caffeine concentration of 2 and 32 mmoL and at 2% halothane, and contraction after 100 Hz stimulation). Results: Mean age of the sample was 35±13.3 years, and most of the subjects were female (n=43 or 54%) and MH susceptible (60%). Of the 20 subjects undergoing genetic investigation, 65% showed variants in RYR1/CACNA1S genes. We found no difference between the positive and negative IVCT groups regarding age, sex, number of probands, presence of muscle weakness or myopathy with muscle biopsy showing cores. Regression analysis revealed that the best predictors of positive IVCT were male sex (+12%), absence of muscle weakness (+20%), and personal MH background (+17%). Conclusions: Positive IVCT results have been correlated to male probands, in accordance with early publications. Furthermore, normal muscle strength has been confirmed as a significant predictor of positive IVCT while investigating suspected MH cases.

Fast gamma oscillations, generated within the retina, and transmitted to the cortex via the lateral geniculate nucleus (LGN), are thought to carry information about stimulus size and continuity. This hypothesis relies mainly on studies conducted under anesthesia and the extent to which it holds under more naturalistic conditions remains unclear. Using multielectrode recordings of spiking activity in the retina and the LGN of both male and female cats, we show that visually driven gamma oscillations are absent for awake states and are highly dependent on halothane (or isoflurane). Under ketamine, responses were nonoscillatory, as in the awake condition. Response entrainment to the monitor refresh was commonly observed up to 120 Hz and was superseded by the gamma oscillatory responses induced by halothane. Given that retinal gamma oscillations are contingent on halothane anesthesia and absent in the awake cat, such oscillations should be considered artifactual, thus playing no functional role in vision. [ABSTRACT FROM AUTHOR]

Ryanodine receptor (RYR) mutations confer stress-triggered malignant hyperthermia (MH) susceptibility. Dietary caffeine (CAF) is the most commonly consumed psychoactive compound by humans. CAF-triggered Ca2+ release and its influences on skeletal muscle contractility are widely used as experimental tools to study RYR function/dysfunction and diagnose MH susceptibility. We hypothesize that dietary CAF achieving blood levels measured in human plasma exacerbates the penetrance of RYR1 MH susceptibility mutations triggered by gaseous anesthetic, affecting both central and peripheral adverse responses. Heterozygous R163C-RYR1 (HET) MH susceptible mice are used to investigate the influences of dietary CAF on both peripheral and central responses before and after induction of halothane (HAL) maintenance anesthesia under experimental conditions that maintain normal core body temperature. HET mice receiving CAF (plasma CAF 893 ng/ml) have significantly shorter times to respiratory arrest compared with wild type, without altering blood chemistry or displaying hyperthermia or muscle rigor. Intraperitoneal bolus dantrolene before HAL prolongs time to respiratory arrest. A pilot electrographic study using subcutaneous electrodes reveals that dietary CAF does not alter baseline electroencephalogram (EEG) total power, but significantly shortens delay to isoelectric EEG, which precedes respiratory and cardiac arrest. CAF ± HAL are studied on RYR1 single-channel currents and HET myotubes to define molecular mechanisms of gene-by-environment synergism. Strong pharmacological synergism between CAF and HAL is demonstrated in both single-channel and myotube preparations. Central and peripheral nervous systems mediate adverse responses to HAL in a HET model of MH susceptibility exposed to dietary CAF, a modifiable lifestyle factor that may mitigate risks of acute and chronic diseases associated with RYR1 mutations. SIGNIFICANCE STATEMENT: Dietary caffeine at a human-relevant dose synergizes adverse peripheral and central responses to anesthesia in malignant hyperthermia susceptible mice. Synergism of these drugs can be attributed to their actions at ryanodine receptors.

Background: Inhalational anaesthetics are used for the induction and maintenance of general anaesthesia in children. More agents are evolving in an effort to discover the agent of choice in this age group, considering the safety margin, availability, affordability, and accessibility of the anaesthetics. Aim: The aim of our study was to compare the qualities of halothane and sevoflurane in paediatric patients. Materials and Methods: This was a prospective randomised study of 100 children within the age group of 5–12 years, scheduled for elective surgery in Ahmadu Bello University Teaching Hospital, Zaria, from January to October 2022, and satisfied the study inclusion criteria. The following variables (heart rate, blood pressure, arrhythmias, and complications) were recorded and analysed using IBM SPSS version 25 (Chicago) USA. P ≤ 0.05 was considered statistically significant. Results: The incidence of tolerability at induction of anaesthesia, hypoxaemia (SpO2

Silylated-acetylated cyclodextrin (CD) derivatives have recently been investigated, via nuclear magnetic resonance (NMR) spectroscopy, as chiral sensors for substrates that are endowed and devoid of fluorine atoms, and the importance of Si-F interaction in the discrimination phenomena has been assessed. Here, the contributions of both superficial interactions and inclusion processes were further evaluated by extending the records to other chiral fluorinated substrates of interest for pharmaceutical applications. Non-equivalences were measured for both the 1H and 19F resonances in equimolar mixtures with the CDs; the promising results also supported the use of chiral sensors in sub-stoichiometric amounts. Finally, the occurrence of inclusion processes was evaluated by analyzing the intermolecular dipolar interactions by means of ROESY (Rotating-frame Overhauser Enhancement Spectroscopy) experiments. The study confirmed that the γCD derivative is the best chiral solvating agent for the fluorinated substrates investigated, likely due to the higher number of silyl moieties that can be involved in Si-F interactions. The contribution of inclusion processes to the enantiodiscrimination was also confirmed by comparison with the α- and β-analogues. Overall, the CD derivatives proved to be able to discriminate fluorinated substrates even when used in sub-stoichiometric amounts. [ABSTRACT FROM AUTHOR]

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Background: Halothane and Isoflurane are two frequent inhalation agents used as maintenance anesthesia during surgery. After experiencing anesthesia, many patients experience decreased hemodynamic status as pressure blood, respiration, and pulse. Because that study this expected could determine proper anesthesia for use. Purpose : evaluates differences in hemodynamic status post-anesthesia consequence use of halothane and isoflurane. Method research: Study this is a study with quasi pre-post design experiment with a control group design. The sample study is all patients undergoing Installation Surgery at Sele Be Solu Hospital, Sorong City, which uses the general anesthesia technique with inhalation of halothane or isoflurane for as many as 21 people. Instrument study use sheet observation to measure pressure, blood, respiration, and pulse During surgery. Research Results: The Wilcoxon test obtained a score of 0.157 on the pressure blood respondent after getting anesthesia halothane and respondents after getting anesthesia isoflurane, i.e., 0.007. significance of 1.000 and 0.317 on pulse respondents who got anesthesia halothane and isoflurane. Significance of 1.000 and 0.083 on respiration respondents who got anesthesia halothane and isoflurane. Mann Whitney test shows changes in blood pressure, pulse, and respiration in anesthetized respondents who used halothane and isoflurane score significance of 0.784, 0.576, and 0.307. Conclusion: There is a difference in blood pressure at first and end anesthesia use of isoflurane. No, there is a difference in frequency pulse, initial pulse, and respiration anesthesia, and end anesthesia use isoflurane.No there is a difference in pressure blood, pulse, and respiration at the beginning and end anesthesia use halothane. There is no difference in blood pressure, pulse, and respiration after general anesthesia uses isoflurane and halothane.

This article discusses the continued use of halothane as an anesthetic, particularly in Africa, despite its removal from most high-income countries due to safety concerns. The author, a practitioner in Cameroon, acknowledges the dangers associated with halothane but highlights its affordability compared to other options. The article explores the complications and adaptations made to ensure safe use of halothane, including the management of myocardial depression and liver toxicity. The author also discusses the longer induction and emergence times of halothane and its advantages in certain surgical procedures. The article concludes by emphasizing the need for better healthcare financing and prioritization to switch to safer alternatives. [Extracted from the article]

The mitochondrial electron transport chain (mETC) contains molecular targets of volatile general anesthetics (VGAs), which places carriers of mutations at risk for anesthetic complications. The ND-2360114 and mt:ND2del1 lines of fruit flies (Drosophila melanogaster) that carry mutations in core subunits of Complex I of the mETC replicate numerous characteristics of Leigh syndrome (LS) caused by orthologous mutations in mammals and serve as models of LS. ND-2360114 flies are behaviorally hypersensitive to volatile anesthetic ethers and develop an age- and oxygen-dependent anesthetic-induced neurotoxicity (AiN) phenotype after exposure to isoflurane but not to the related anesthetic sevoflurane. The goal of this paper was to investigate whether the alkane volatile anesthetic halothane and other mutations in Complex I and in Complexes II–V of the mETC cause AiN. We found that (i) ND-2360114 and mt:ND2del1 were susceptible to toxicity from halothane; (ii) in wild-type flies, halothane was toxic under anoxic conditions; (iii) alleles of accessory subunits of Complex I predisposed to AiN; and (iv) mutations in Complexes II–V did not result in an AiN phenotype. We conclude that AiN is neither limited to ether anesthetics nor exclusive to mutations in core subunits of Complex I. [ABSTRACT FROM AUTHOR]

General anesthetic drugs have been associated with various unwanted effects including an interference with mitochondrial function. We had previously observed increases of lactate formation in the mouse brain during anesthesia with volatile anesthetic agents. In the present work, we used mitochondria that were freshly isolated from mouse brain to test mitochondrial respiration and ATP synthesis in the presence of six common anesthetic drugs. The volatile anesthetics isoflurane, halothane, and (to a lesser extent) sevoflurane caused an inhibition of complex I of the electron transport chain in a dose-dependent manner. Significant effects were seen at concentrations that are reached under clinical conditions (< 0.5 mM). Pentobarbital and propofol also inhibited complex I but at concentrations that were two-fold higher than clinical EC50 values. Only propofol caused an inhibition of complex II. Complex IV respiration was not affected by either agent. Ketamine did not affect mitochondrial respiration. Similarly, all anesthetic agents except ketamine suppressed ATP production at high concentrations. Only halothane increased cytochrome c release indicating damage of the mitochondrial membrane. In summary, volatile general anesthetic agents as well as pentobarbital and propofol dose-dependently inhibit mitochondrial respiration. This action may contribute to depressive actions of the drugs in the brain. [ABSTRACT FROM AUTHOR]

Patient immobilisation with volatile anaesthetics (VA) during radiotherapy is sometimes unavoidable. Although it is known that both VAs and ionising radiation can have nephrotoxic effects, there are no studies of their combined effects on DNA damage. The aim of this in vivo study was to address this gap by investigating whether 48 groups of healthy Swiss albino mice (totalling 240) would differ in kidney cell DNA damage response (alkaline comet assay) to isoflurane, sevoflurane, or halothane anaesthesia and exposure to 1 Gy or 2 Gy of ionising radiation. We took kidney cortex samples after 0, 2, 6, and 24 h of exposure and measured comet parameters: tail length and tail intensity. To quantify the efficiency of the cells to repair and re-join DNA strand breaks, we also calculated cellular DNA repair index. Exposure to either VA alone increased DNA damage, which was similar between sevoflurane and isoflurane, and the highest with halothane. In combined exposure (VA and irradiation with 1 Gy) DNA damage remained at similar levels for all time points or was even lower than damage caused by radiation alone. Halothane again demonstrated the highest damage. In combined exposure with irradiation of 2 Gy sevoflurane significantly elevated tail intensity over the first three time points, which decreased and was even lower on hour 24 than in samples exposed to the corresponding radiation dose alone. This study confirmed that volatile anaesthetics are capable of damaging DNA, while combined VA and 1 Gy or 2 Gy treatment did not have a synergistic damaging effect on DNA. Further studies on the mechanisms of action are needed to determine the extent of damage in kidney cells after longer periods of observation and how efficiently the cells can recover from exposure to single and multiple doses of volatile anaesthetics and radiotherapy.

Cell–cell communication via gap junction channels is known to be inhibited by the anesthetics heptanol, halothane and isoflurane; however, despite numerous studies, the mechanism of gap junction channel gating by anesthetics is still poorly understood. In the early nineties, we reported that gating by anesthetics is strongly potentiated by caffeine and theophylline and inhibited by 4-Aminopyridine. Neither Ca2+ channel blockers nor 3-isobutyl-1-methylxanthine (IBMX), forskolin, CPT-cAMP, 8Br-cGMP, adenosine, phorbol ester or H7 had significant effects on gating by anesthetics. In our publication, we concluded that neither cytosolic Ca2+i nor pHi were involved, and suggested a direct effect of anesthetics on gap junction channel proteins. However, while a direct effect cannot be excluded, based on the potentiating effect of caffeine and theophylline added to anesthetics and data published over the past three decades, we are now reconsidering our earlier interpretation and propose an alternative hypothesis that uncoupling by heptanol, halothane and isoflurane may actually result from a rise in cytosolic Ca2+ concentration ([Ca2+]i) and consequential activation of calmodulin linked to gap junction proteins. [ABSTRACT FROM AUTHOR]

Anaesthetic agents and doses used can significantly impact cerebrocortical responsiveness as assessed by electroencephalography (EEG). The objective of this study was to evaluate the effect of three different halothane concentrations on the EEG of Rock Doves using measures of frequency distribution and burst suppression. Eight healthy Rock Doves (Columba livia) were anaesthetized with halothane in oxygen, their tracheas intubated and their lungs mechanically ventilated. Five minutes of EEG were recorded at three multiples of minimum anaesthetic concentration (MAC), 1× MAC (1.6%), 1.5× MAC (2.4%) and 2× MAC (3.2%), presented in ascending then descending order. Fast Fourier transformation of the raw EEG record gave the median frequency (F50), spectral edge frequency (F95) and the total power (Ptot). Burst suppression, expressed as inactive compared to active EEG (%), was calculated on a representative two-minute section of the raw EEG. Data were analysed using repeated-measures one-way ANOVA with Tukey post hoc correction for comparison of 1×, 1.5× and 2× MAC. Three of eight birds demonstrated negligible (F50, p = 0.04; F95p = 0.02; Ptotp < 0.0001) occurred between 1× and 2× MAC. Halothane anaesthesia at MAC multiples of 1×, 1.5× and 2× in the Rock Dove can be considered suitable where cortical responsiveness is desired.

A well-equipped anesthesia workstation is a boon for better anesthesia practice. Advancement in technical aspects such as respiratory gas analysis made perioperative care better and safer. Any kind of equipment troubleshoot can contribute to morbidity and mortality; however, the magnitude of these is not established.

We assessed concentration-dependent effects of halothane or isoflurane inhalation on the electrocardiographic and hemodynamic variables using a cross-over design in intact beagle dogs (n = 4). Elevation of inhaled halothane from 1.0% to 2.0% or isoflurane from 1.5% to 2.5% decreased the mean blood pressure and prolonged the QRS width without significantly altering the heart rate, PR interval or QT interval. However, the observed changes disappeared after regressions of both anesthetic conditions to their initial settings. These results indicate that hypotension-induced, reflex-mediated increase of sympathetic tone may have counterbalanced the direct negative chronotropic, dromotropic and repolarization slowing effects of the anesthetics.

Silylated-acetylated cyclodextrin (CD) derivatives have recently been investigated, via nuclear magnetic resonance (NMR) spectroscopy, as chiral sensors for substrates that are endowed and devoid of fluorine atoms, and the importance of Si-F interaction in the discrimination phenomena has been assessed. Here, the contributions of both superficial interactions and inclusion processes were further evaluated by extending the records to other chiral fluorinated substrates of interest for pharmaceutical applications. Non-equivalences were measured for both the 1H and 19F resonances in equimolar mixtures with the CDs; the promising results also supported the use of chiral sensors in sub-stoichiometric amounts. Finally, the occurrence of inclusion processes was evaluated by analyzing the intermolecular dipolar interactions by means of ROESY (Rotating-frame Overhauser Enhancement Spectroscopy) experiments. The study confirmed that the γCD derivative is the best chiral solvating agent for the fluorinated substrates investigated, likely due to the higher number of silyl moieties that can be involved in Si-F interactions. The contribution of inclusion processes to the enantiodiscrimination was also confirmed by comparison with the α- and β-analogues. Overall, the CD derivatives proved to be able to discriminate fluorinated substrates even when used in sub-stoichiometric amounts.

Experiments on pulmonary pharmacology are often performed in laboratory animals. Investigators collect organs, samples, or record modifications in the respiratory system during anaesthesia, which might significantly influence the data attained. Indeed, it is recommended to cautiously select the anaesthetic adapted for lung studies. This experiment aimed to evaluate three selected anaesthetics usually used in laboratory animal experiments, namely, (Zoliterumpon (Z+R) mixture, halothane (HAL), and urethane (URE)) in rats. Rats were divided into four groups, control group, kept without treatment; Zolitel and Rumpon (Z+R) at a dose of 5 and 30 mg/kg body weight intraperitoneally, respectively; HAL group (5% with oxygen supply), and URE (1.5 mg/kg body weight) by inhalation. Blood samples were collected to determine the pH of the blood, bicarbonate (HCO3 -), carbon dioxide partial pressure (pCO2), oxygen partial pressure (pO2), alveolar oxygen (A), saturated oxygen (O2 Sat), magnesium (Mg2+), calcium (Ca2+), sodium (Na+), potassium (K+), and chloride (Cl-) ions, haematocrit (Hct), and haemoglobin (Hb). The result indicates that the Z+R mixture causes slight to no differences in the measured data. At the same time, HAL and URE greatly reduced the blood pH and significantly disrupted the values of HCO3-, pCO2, pO2, A, and O2 Sat. Together, HAL and URE induced metabolic acidosis and respiratory depression. Hence, the Z+R mix is suitable for the three anaesthetics pulmonary pharmacology experiments. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Industrial Hygiene & Toxicology / Arhiv za Higijenu Rada I Toksikologiju is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We compared dl-sotalol-induced electrocardiographic responses in intact dogs using a repeated-measures design among 1% halothane anesthesia, 1.5% isoflurane anesthesia with nitrous oxide (N2O), and conscious state to clarify influences of the anesthetics (n = 4). Basal PR interval was longer in halothane than either in isoflurane with N2O or in conscious state, reflecting sympathetic nerve suppression for the atrioventricular node by halothane. Both anesthetics exhibited longer basal QRS width than conscious state, suggesting their ventricular INa inhibition. Also, both anesthetics showed longer basal QT interval, QTcF and Tpeak-Tend than conscious state, indicating their ventricular IKr inhibition. Meanwhile, dl-sotalol prolonged PR interval similarly in isoflurane with N2O and in conscious state, which was less great in halothane, suggesting further sympathetic nerve suppression for the atrioventricular node might be limited in halothane. dl-Sotalol prolonged QT interval and QTcF >3 times greater in either of the anesthetics than in conscious state; moreover, dl-sotalol prolonged Tpeak-Tend similarly in both anesthetics, but hardly altered it in conscious state; indicating isoflurane with N2O as well as halothane may have reduced the repolarization reserve to increase the sensitivity of ventricle toward IKr suppression. Thus, isoflurane with nitrous oxide could be useful for in vivo IKr assay like halothane.

An efficient and convenient method for the synthesis of structurally unique and highly functionalized aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers has been developed. This approach exhibits a broad reaction scope, a simple operation and without the need of any expensive transition-metal catalyst, highly toxic or corrosive reagents. Notably, we demonstrate the potential utility of halothane for the synthesis of aryl gem-difluoroalkyl ethers containing the bromochloromethyl group.

BackgroundThe effects of anesthesia on the equine electroencephalogram (EEG) after administration of various drugs for sedation, induction, and maintenance are known, but not that the effect of inhaled anesthetics alone for EEG recording.ObjectiveTo determine the effects of isoflurane and halothane, administered as single agents at multiple levels, on the EEG and quantitative EEG (qEEG) of normal horses.AnimalsSix healthy horses.MethodsProspective study. Digital EEG with video and quantitative EEG (qEEG) were recorded after the administration of one of the 2 anesthetics, isoflurane or halothane, at 3 alveolar doses (1.2, 1.4 and 1.6 MAC). Segments of EEG during controlled ventilation (CV), spontaneous ventilation (SV), and with peroneal nerve stimulation (ST) at each MAC multiple for each anesthetic were selected, analyzed, and compared. Multiple non-EEG measurements were also recorded.ResultsSpecific raw EEG findings were indicative of changes in the depth of anesthesia. However, there was considerable variability in EEG between horses at identical MAC multiples/conditions and within individual horses over segments of a given epoch. Statistical significance for qEEG variables differed between anesthetics with bispectral index (BIS) CV MAC and 95% spectral edge frequency (SEF95) SV MAC differences in isoflurane only and median frequency (MED) differences in SV MAC with halothane only.Conclusions and clinical importanceUnprocessed EEG features (background and transients) appear to be beneficial for monitoring the depth of a particular anesthetic, but offer little advantage over the use of changes in mean arterial pressure for this purpose.

BackgroundPrevious study of the diagnostic validity of electroencephalography (EEG) to detect abnormalities in equine cerebral cortical function relied on the administration of various drugs for sedation, induction, and maintenance of general anesthesia but used identical criteria to interpret recordings.ObjectivesTo determine the effects of 2 inhalation anesthetics on the EEG of healthy horses.AnimalsSix healthy horses.MethodsProspective study. After the sole administration of one of either isoflurane or halothane at 1.2, 1.4, and 1.6 times the minimum alveolar concentration, EEG was recorded during controlled ventilation, spontaneous ventilation, and nerve stimulation.ResultsBurst suppression was observed with isoflurane, along with EEG events that resembled epileptiform discharges. Halothane results were variable between horses, with epileptiform-like discharges and bursts of theta, alpha, and beta recorded intermittently. One horse died and 2 were euthanized as the result of anesthesia-related complications.Conclusions and clinical importanceThe results of this study indicate that the effects of halothane and isoflurane on EEG activity in the normal horse can be quite variable, even when used in the absence of other drugs. It is recommended that equine EEG be performed without the use of these inhalation anesthetics and that general anesthesia be induced and maintained by other contemporary means.

A new species of bent-toed geckos of the genus Cyrtodactylus is described from western Arunachal Pradesh. The new species is a member of the Indo-Burma clade and is embedded within the "peguensis" group, a relationship deduced contingent on a partial fragment of mitochondrial NADH subunit 2 gene. Cyrtodactylus kamengensis sp. nov. is morphologically similar to C. himalayicus from which it differs in bearing a distinct ventrolateral fold and 6-8 basal lamellae on digit IV of pes. Genetically, the new species is sister to the Indian lineage of the "peguensis" group containing C. bhupathyi and C. gubernatoris. The Indian lineage of the "peguensis" group diverged from its Burmese relatives during the mid-Oligocene likely followed by the beginning of the Himalayan uplift, highlighting the role of the Himalayas in the diversification of biota. [ABSTRACT FROM AUTHOR]

This article examines how chemists, pharmacologists and anaesthetists developed the anaesthetic drug halothane and assessed the clinical use of the drug in the UK in the 1950s. I argue that halothane became seen as a superior drug not because of properties inherent in the new molecule CF3-CHClBr, but because anaesthetists used it to build a professional identity during a period of significant change in British medicine. The recently established National Health Service called for increasing the number of anaesthetists and other specialist hospital consultants. In this context, the specialist knowledge, novel technologies and new practices necessary for the safe usage of halothane enabled anaesthetists to forge a profession. The history of this process shows how professionalisation, pharmaceutical change and healthcare reform have interacted to shape knowledge transfer between laboratory and hospital with consequences for experimental ethics and patient safety. [ABSTRACT FROM AUTHOR]

Patient immobilization by general volatile anesthesia (VA) may be necessary during medical radiology treatment, and its use has increased in recent years. Although ionizing radiation (IR) is a well-known genotoxic and cytotoxic agent, and VA exposure has caused a range of side effects among patients and occupationally exposed personnel, there are no studies to date comparing DNA damage effects from combined VA and single fractional IR dose exposure. We investigate whether there is a difference in white blood cells DNA damage response (by the alkaline comet assay) in vivo in 185 healthy Swiss albino mice divided into 37 groups, anesthetized with isoflurane/sevoflurane/halothane and exposed to 1 or 2 Gy of IR. Blood samples were taken after 0, 2, 6 and 24 h after exposure, and comet parameters were measured: tail length, tail intensity and tail moment. The cellular DNA repair index was calculated to quantify the efficiency of cells in repairing and re-joining DNA strand breaks following different treatments. In combined exposures, halothane caused higher DNA damage levels that were dose-dependent; sevoflurane damage increase did not differ significantly from the initial 1 Gy dose, and isoflurane even demonstrated a protective effect, particularly in the 2 Gy dose combined exposure. Nevertheless, none of the exposures reached control levels even after 24 h. Halothane appears to increase the level of radiation-induced DNA damage, while sevoflurane and isoflurane exhibited a protective effect. DNA damage may have been even greater in target organs such as liver, kidney or even the brain, and this is proposed for future study. [ABSTRACT FROM AUTHOR]

Malignant hyperthermia (MH) is potentially fatal pharmacogenetic disorder of skeletal muscle caused by intracellular Ca(2+) dysregulation. NCX is a bidirectional transporter that effluxes (forward mode) or influxes (reverse mode) Ca(2+) depending on cellular activity. Resting intracellular calcium ([Ca(2+)]r) and sodium ([Na(+)]r) concentrations are elevated in MH susceptible (MHS) swine and murine muscles compared with their normal (MHN) counterparts, although the contribution of NCX is unclear. Lowering [Na(+)]e elevates [Ca(2+)]r in both MHN and MHS swine muscle fibers and it is prevented by removal of extracellular Ca(2+) or reduced by t-tubule disruption, in both genotypes. KB-R7943, a nonselective NCX3 blocker, reduced [Ca(2+)]r in both swine and murine MHN and MHS muscle fibers at rest and decreased the magnitude of the elevation of [Ca(2+)]r observed in MHS fibers after exposure to halothane. YM-244769, a high affinity reverse mode NCX3 blocker, reduces [Ca(2+)]r in MHS muscle fibers and decreases the amplitude of [Ca(2+)]r rise triggered by halothane, but had no effect on [Ca(2+)]r in MHN muscle. In addition, YM-244769 reduced the peak and area under the curve of the Ca(2+) transient elicited by high [K(+)]e and increased its rate of decay in MHS muscle fibers. siRNA knockdown of NCX3 in MHS myotubes reduced [Ca(2+)]r and the Ca(2+) transient area induced by high [K(+)]e. These results demonstrate a functional NCX3 in skeletal muscle whose activity is enhanced in MHS. Moreover reverse mode NCX3 contributes to the Ca(2+) transients associated with K(+)-induced depolarization and the halothane-triggered MH episode in MHS muscle fibers.

Cell–cell communication via gap junction channels is known to be inhibited by the anesthetics heptanol, halothane and isoflurane; however, despite numerous studies, the mechanism of gap junction channel gating by anesthetics is still poorly understood. In the early nineties, we reported that gating by anesthetics is strongly potentiated by caffeine and theophylline and inhibited by 4-Aminopyridine. Neither Ca2+ channel blockers nor 3-isobutyl-1-methylxanthine (IBMX), forskolin, CPT-cAMP, 8Br-cGMP, adenosine, phorbol ester or H7 had significant effects on gating by anesthetics. In our publication, we concluded that neither cytosolic Ca2+i nor pHi were involved, and suggested a direct effect of anesthetics on gap junction channel proteins. However, while a direct effect cannot be excluded, based on the potentiating effect of caffeine and theophylline added to anesthetics and data published over the past three decades, we are now reconsidering our earlier interpretation and propose an alternative hypothesis that uncoupling by heptanol, halothane and isoflurane may actually result from a rise in cytosolic Ca2+ concentration ([Ca2+]i) and consequential activation of calmodulin linked to gap junction proteins.

The IR absorption spectra of solutions of mixtures of halothane (C2HBrClF3) and trimethylamine ((CD3)3N) in liquefied krypton were obtained and analyzed. Bands assigned to weak hydrogen-bonded complexes have been identified. In a series of temperature experiments on the change in the integral intensities of the bands of monomers and complexes, the enthalpy of formation of complexes was estimated. An extremely strong increase in the intensity of the second-order bands attributed to the first overtone of bending CH vibrations of halothane was found. The effect is determined by strong anharmonic interactions of a resonant nature (Fermi resonance and Darling–Dennison resonance). The results of ab initio calculations reproduce the experimentally observed effects. [ABSTRACT FROM AUTHOR]

Experiments have shown that general anaesthetics lose their efficacy at pressures of around 20 MPa, but their efficacy is recovered at pressures of around 40 MPa. Molecular dynamics simulations of the general anaesthetic halothane in DMPC or POPC bilayers show that halothane aggregates inside the membrane at 20 MPa, but not at atmospheric pressure, nor at 40 MPa. The parallelism in effects suggests that aggregation could conceivably be the mechanism for pressure reversal. Further molecular dynamics simulations of another general anaesthetic, isoflurane, in POPC show that isoflurane does not aggregate at 20 MPa. This and other quantitative considerations show that general anaesthetic aggregation inside the membrane could not be the mechanism for pressure reversal. [ABSTRACT FROM AUTHOR]

Background: Malignant hyperthermia (MH) susceptibility is an inherited condition, diagnosed either by the presence of a pathogenic genetic variant or by in vitro caffeine-halothane contracture testing. Through a multi-dimensional approach, we describe the implications of discordance between genetic and in vitro test results in a patient with a family history of possible MH.Methods: The patient, whose brother had a possible MH reaction, underwent the caffeine-halothane contracture test (CHCT) according to the North American MH Group protocol. Screening of the complete RYR1 and CACNA1S transcripts was done using Sanger sequencing. Additional functional analyses included skinned myofibre calcium-induced calcium release sensitivity, calcium signalling assays in cultured myotubes, and in silico evaluation of the effect of any genetic variants on their chemical environment.Results: The patient's CHCT result was negative but she carried an RYR1 variant c.1209C>G, p.Ile403Met, that is listed as pathogenic by the European Malignant Hyperthermia Group. Functional tests indicated a gain-of-function effect with a weak impact, and the variant was predicted to affect the folding stability of the 3D structure of the RyR1 protein. Based on American College of Medical Genetics and Genomics/Association of Molecular Pathology guidelines, this variant would be characterised as a variant of uncertain significance.Conclusions: Available data do not confirm or exclude an increased risk of MH for this patient. Further research is needed to correlate RyR1 functional assays, including the current gold standard testing for MH susceptibility, with clinical phenotypes. The pathogenicity of genetic variants associated with MH susceptibility should be re-evaluated. [ABSTRACT FROM AUTHOR]

The standing outward K(+) current (IKso) governs the response of cerebellar granule neurons to natural and medicinal stimuli including volatile anesthetics. We showed that SUMOylation silenced half of IKso at the surface of cerebellar granule neurons because the underlying channels were heterodimeric assemblies of K2P1, a subunit subject to SUMOylation, and the TASK (two-P domain, acid-sensitive K(+)) channel subunits K2P3 or K2P9. The heterodimeric channels comprised the acid-sensitive portion of IKso and mediated its response to halothane. We anticipate that SUMOylation also influences sensation and homeostatic mechanisms in mammals through TASK channels formed with K2P1.

Abstract Objective Halothane and caffeine are known to cause skeletal muscular contractions in vitro and have been proven to induce circumscribed metabolic reactions when injected into rat skeletal muscle. In this study 26 rats were investigated by either continuous application of calcium 160 mM or bolus injection of caffeine 160 mM or halothane 10% vol via a microdialysis probe in the tibialis anterior muscle. Tissue elasticity at the injection site was monitored by ultrasound strain elastography. Aim of this study was to detect (I) changes in local lactate concentrations and (II) whether these can be attributed to a muscular contraction detected by ultrasound elastography. Results Localized metabolic reactions were verified by increasing intramuscular lactate concentrations following continuous application of calcium (0.6 [0.3;0.6] to 3.6 [3.0;4.3] mmol/l after 60 min) and bolus application of caffeine (0.2 [0.2;0.3] to 1.6 [0.9;1.9] mmol/l after 30 min) and halothane (0.3 [0.1;0.3] to 4.7 [4.3;6.3] mmol/l after 30 min). However, ultrasound elastography did not detect any differences in tissue elasticity compared to control animals. The authors identified potential limitations of the study conditions, which might be crucial to avoid for future investigations.

In this review article, inhalational anesthetics agents and their pharmacokinetic, pharmacodynamics and effects on the central nervous, cardiovascular, and respiratory systems are discussed. There is a wide spectrum of inhalational anesthetic agents with different characteristics. As some examples, in this study, recovery times of sevoflurane and halothane are reviewed. Overall, gas drugs have extensive usage in Intensive Care Unit. For example, a combination of oxygen and helium may be utilized in patients with obstructive airway disorders, endotracheal tubes, acute lung damage, diphtheria, respiratory distress syndrome, asthma, bronchiolitis, and chronic obstructive pulmonary disease. Xenon would be effective in reducing memories after traumatic events.

Goal: to develop the design of the experiment for evaluation of cognitive functions and behavior of rats after some aggressive impact imitating anesthesia and surgery in the clinical practice. Methods: Male rats of Wistar stock (n = 40) were used to evaluate long-term behavioral effects of the abdomen surgery and short-term (15-20 min.) and long-term (6 hours) actions of halothane. Simple (2x2) factorial plan was used for the experiment (4 blocks, balanced as per the number of animals from 4 experimental groups, n=2 for each group in the block). For anesthesia induction 4 volumes of % halothane in the air flow (2 l/min) were used, for anesthetic support it was 1.5 volume of % halothane. During surgery the rat was placed on the heated operating table and the mask was used for anesthesia. Laparotomy was performed; empty intestine was identified and irritated for 10 seconds by massage movement of the forefinger and thumb. After that the loop was placed into the abdomen and the wound was sutured layer by layer. Then for three weeks the following behavioral tests were performed in compliance with the protocol: motor activity (Actometer) and exploratory activity in new environment (Open field), social behavior (pair interaction test), novel object recognition, extrapolational deliverance rate, forced swimming, sexual behavior. Ovariectomized female (n = 16) were used as standard opponents for social behavior tests, and hormone-stimulated female rats (n = 26) were used for sexual behavior tests. The results showed that long-term action of halothane vapor caused behavioral changes in rats: it reduces exploratory activity, decreases the novel object recognition index, increases immobility during forced swimming and reduces latent period of extrapolational deliverance. Halothane made no significant impact on motor activity (open field) and sexual behavior of male rats. In general the results of performed tests provide evidence of emotional flattening development in rats. Conclusion: It is feasible to use the experiment design and pool of behavioral tests used in this study for experimental evaluation of inhalation anesthetics effects, their late consequences, and also for searching the ways of management of the developing behavioral disorders.

A well-equipped anesthesia workstation is a boon for better anesthesia practice. Advancement in technical aspects such as respiratory gas analysis made perioperative care better and safer. Any kind of equipment troubleshoot can contribute to morbidity and mortality; however, the magnitude of these are not established. [ABSTRACT FROM AUTHOR]

Inhalational anesthetics are used for induction and maintenance of general anesthesia in the operating room. The volatile anesthetics (halothan, isoflurane, desflurane, and sevoflurane) are liquids and nitrous oxide is gas under normal temperature and pressure. All inhalational anesthetics provide dose-dependent amnesia and immobility, except for nitrous oxide, which also provides analgesia. This review article brings information about effects on organs, clinical use of the currently used anesthetics, their advantages and limitations. [ABSTRACT FROM AUTHOR]