Inhalation anesthesia is preferable for recording rat cardiac function using an electrocardiogram.

The effects of inhalation anesthesia (2% isoflurane, sevoflurane, or enflurane) and intraperitoneal anesthesia with pentobarbital (65 mg/kg) were compared in rats using an electrocardiogram (ECG) and determination of blood oxygen saturation (SPO2) levels. Following inhalation anesthesia, heart rate (HR) and SPO2 were acceptable while pentobarbital anesthesia decreased HR and SPO2 significantly. This indicates that inhalation anesthesia is more preferable than pentobarbital anesthesia when evaluating cardiovascular factors. Additionally, pentobarbital significantly increased HR variability (HRV), suggesting a regulatory effect of pentobarbital on the autonomic nervous system, and resulted in a decreased response of the baro-reflex system. Propranolol or atropine had limited effects on ECG recording following pentobarbital anesthesia. Taken together, these data suggest that inhalation anesthesia is suitable for conducting hemodynamic analyses in the rat.

[Effect of volatile inhalational anesthetics on cerebral blood volume and oxygen status in children].

The investigation evaluated the effect of various volatile anesthetics on cerebral blood volume and oxygen status in sick children at the stage of anesthesia induction. Ninety-two children were distributed into 3 groups: Groups 1 (n = 36) and 2 (n = 24) underwent stepwise induction with halothane and enflurane, respectively. Group 3 (n = 32) had vital capacity rapid inhalation induction with sevoflurane. Cerebral oximetry (NIRS method) was used to measure the content of hydroxyhemoglobin, deoxyhemoglobin, the total level of hemoglobin and to assess regional cerebral tissue saturation (rSO2). Halothane was ascertained to increase cerebral blood volume by 20.5% whereas enflurane and sevoflurane increased it only by 8.8 and 9.0%, respectively. In all cases, the value of rSO2 remained comparatively high, by exceeding the baseline level by 3-5%.

Serotonin, estrus, and social context influence c-Fos immunoreactivity in the inferior colliculus.

A fundamental task of sensory systems is to extract relevant social information from a range of environmental stimuli in the face of changing behavioral contexts and reproductive states. Neuromodulatory pathways that interact with such contextual variables are 1 mechanism for achieving this. In the mouse inferior colliculus (IC), a midbrain auditory region, the neuromodulator serotonin increases in females interacting with courting males, but events downstream of serotonin release have not been investigated. Here, we manipulated serotonin levels in female mice with the serotonin releaser fenfluramine or the serotonin depleter para-chlorophenylalaninemethyl ester (pCPA). Females were then exposed to an empty cage, a male partner, or a playback of courtship vocalizations, and the numbers of neurons in the IC with positive immunoreactivity for the immediate early gene product c-Fos were measured. The effects of drug treatments depended on social context and estrous state. Fenfluramine had greater effects in the nonsocial than in the partner social treatments. Females in proestrus or estrus and given fenfluramine had higher densities of c-Fos immunoreactive neurons, while females in diestrus had fewer immunoreactive neurons. The drug pCPA had the expected opposite effect of fenfluramine, causing a decreased response in pro/estrus females and an increased response in diestrus females. These findings show that the effects of serotonin on c-Fos activity in the IC of females is dependent on both external context and reproductive state, and suggest that these effects occur downstream of serotonin release. (PsycINFO Database Record

[Effects of volatile anesthetics on cortical somatosensory evoked potential and Bispectral index].

OBJECTIVE: To improve the anesthetic environment in monitoring short-latency somatosensory evoked potentials (SSEP) during operation, we compared the effects of different anesthetics on SSEP and Bispectral index (BIS), which aim to select suitable anesthetics and their doses used intraoperatively. METHODS: 60 ASA I-II patients undergoing elective neurosurgery were randomly allocated into three groups: enflurane, isoflurane and desflurane group. The concentration of each volatile anesthetic was increased step by step from 0 to end-tidal 0.3, 0.5, 0.75, 1.0 and 1.5 MAC. The changes of cortical SSEP component N20 were recorded as well as Bispectral index (BIS) monitoring. The effects of three volatile anesthetics in various concentrations on short-latency SSEP and BIS were investigated. RESULTS: All three volatile anesthetics significantly decreased N20 amplitude and prolonged N20 latency. The N20 waveform disappeared in some patients when the end-tidal concentration of enflurane reached 1.0 MAC, it occurred when that of isoflurane or desflurane was at 1.5 MAC. BIS monitoring showed BIS values were all under 60 when at 1.0 MAC in three group. For some patients in enflurane group and desflurane group, BIS values were above 60 (45-64, 44-61, respectively) when at 0.75 MAC, while those in isoflurane group were still less than 60 (39-58). And the amplitude or latency of cortical SSEP correlated poorly with BIS. CONCLUSION: The effects of three volatile anesthetics on SSEP and BIS are significant in dose-dependent manner. Anesthetic regimen of 0.75 MAC isoflurane for intraoperative cortical SSEP monitoring may be optimal. It seemed that the correlation between BIS and short-latency SSEP was poor, although both are associated with the effects of anesthetics on cerebral cortex.

Retinal tissue oxygen tension in normoxic cats under enflurane anesthesia.

PURPOSE: General anesthesia reduces systemic blood pressure and, thus, ocular perfusion pressure (at constant intraocular pressure). Whether this reduction in ocular perfusion pressure produces retinal hypoxia is unknown. To answer this question, the authors measured inner retinal oxygen tension in cats under general enflurane anesthesia at three clinically relevant levels of anesthesia under normoxic conditions. METHODS: Polarographic oxygen microelectrodes were used to measure inner retinal oxygen tension in cats under enflurane anesthesia at 21% inspired oxygen tension. Measurements were made in the preretinal vitreous body within 100 to 200 microns of the internal limiting membrane of the retina. Three levels of enflurane anesthesia were used: 1.2%, 2.4%, and 3.6%, corresponding to 0.5, 1.0, and 1.5 minimal alveolar concentration. Intraocular pressure of the cats was maintained at a constant normal level throughout the experiments. RESULTS: Under normoxic conditions, inner retinal oxygen tension remained unchanged or increased slightly as ocular perfusion pressure decreased with deeper levels of enflurane anesthesia. CONCLUSION: Commonly used surgical levels of enflurane general anesthesia do not cause hypoxia of the inner retina in cats breathing 21% inspired oxygen. This may be the result of preservation of retinal vascular autoregulation under enflurane anesthesia, retinal vasodilatation secondary to a direct smooth muscle relaxing effect of enflurane, or decreased retinal oxygen use under enflurane anesthesia.

Transient neuromuscular impairment resulting from prolonged inhalation of halothane and enflurane.

Inhalation anesthesia first with halothane followed by enflurane relieved a patient with status asthmaticus who was refractory to conventional therapy including mechanical ventilation. After 13 days of anesthesia while on mechanical ventilation and employing nondepolarizing muscle relaxants, significant neuromuscular impairment, manifested by tetraplegia and sensory disturbance, developed. Anesthesia was discontinued on day 14, and the patient was weaned from mechanical ventilation on day 16. Over the next two months, the neuromuscular impairment markedly improved. Halothane was associated with cardiac arrhythmias and hepatitis necessitating replacement by enflurane. Enflurane appeared to be as effective a treatment for refractory asthma as halothane. The most probable cause of the neuromuscular impairment in our patient was the long-term use of inhalation anesthetics or nondepolarizing muscle relaxants.

Postpartum uterine pressures under halothane or enflurance anesthesia.

Postpartum uterine pressures were measured in healthy women with an intrauterine microballoon before, during, and after administration of different concentrations of halothane or enflurane. Arterial blood samples for anesthetic levels were obtained at intervals. Frequency and intensity of contractions diminished markedly when blood levels exceeded the equivalent of 1/2 MAC (minimum alveolar anesthetic concentration which produces immobility in one-half of subjects exposed to a noxious stimulus) of nonpregnant adults, but normal patterns returned promptly on lightening of anesthesia. Response to 10 mU of oxytocin was suppressed at blood levels corresponding to between 3/4 and 1 MAC of the agents. Halothane and enflurane exert equipotent dose-related reversible effects on the activity of the full-term pregnant human uterus.

Respiratory reflex responses to stimulation of tracheal mucosa in enflurane-anesthetized humans.

We investigated respiratory reflex responses to tracheal mucosa stimulation induced by injection of distilled water in 13 female patients under three different depths of enflurane anesthesia (0.7, 1.0, and 1.3 minimum alveolar concentration). Detailed analysis of the types of reflex responses revealed that there are at least six different responses: 1) the apneic reflex, 2) the expiration reflex, 3) spasmodic, panting breathing, 4) the cough reflex, 5) slowing of breathing, and 6) rapid, shallow breathing. Among these reflex responses, the cough reflex was the most sensitive and the apneic reflex followed by slowing of breathing was the most resistant to deepening anesthesia, whereas the sensitivity of other types of reflex responses was in between. Our results indicate that the types of respiratory reflex responses to tracheal mucosa stimulation are associated with depths of anesthesia and that the differences in sensitivity to anesthesia may be a valuable sign in clinical assessment of depth of anesthesia.

Factors that determine the hemodynamic response to inhalation anesthetics.

The hemodynamic response to inhalation anesthesia is influenced by three factors: 1) the specific drug, 2) the dose, and 3) individual characteristics of the subject. To investigate the importance of these factors on the cardiovascular response, we administered five doses [0, 0.5, 1.0, 1.5, and 2.0 minimum alveolar concentration (MAC)] of enflurane, halothane, and isoflurane to each of six dogs. Twelve hemodynamic variables were measured. For all variables, a change in the dose of each drug produced a consistent effect in each dog. Increases in dose resulted in significant decreases in seven variables [left ventricular ejection fraction, cardiac index (CI), stroke volume index (SVI), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), left ventricular stroke work index (LVSWI), and heart rate (HR)] and a significant increase in one variable [central venous pressure (CVP)]. In contrast, the response of individual dogs to different drugs was not consistent. For seven variables [MAP, MPAP, LVSWI, CVP, pulmonary capillary wedge pressure (PCWP), end-diastolic volume index (EDVI), and end-systolic volume index (ESVI)], a significant difference in the responses of a dog to two drugs was greater than zero, whereas a significant difference in the response of at least one other dog to the same two drugs was less than zero (discordant dog-drug interactions). Thus, in contrast to the consistency of the cardiovascular response to changes in dose, the hemodynamic response to different drugs was inconsistent among dogs. We also studied the effect of fluid challenge on hemodynamic response at 1.5 or 2.0 MAC of the three drugs given to each dog.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of choice of anesthetic with vagotomy testing.

Incomplete vagotomy is the most important cause of recurrent ulcer disease. Despite this, intraoperative vagotomy testing has not gained widespread acceptance. We used a technique with Congo red, a nontoxic azine dye that turns black (pH, 3.0) intraoperatively. The vagolytic effects of various general anesthetics has been shown. We found that halothane, used as a general anesthetic, combined with pentagastrin administration as a vagally synergistic stimulant, produced the most reliable, safe, and reproducible result when using Congo red intraoperatively.

Recovery of LV contractility in man is enhanced by preischemic administration of enflurane.

BACKGROUND: Volatile anesthetics enhance postischemic functional recovery in animal models; this effect has not been investigated in man. METHODS: Twenty-two patients undergoing coronary surgery were randomized to enflurane administration (0.5% to 2%) for 5 minutes to reduce systolic blood pressure by 20% to 25% immediately before cardioplegic arrest. Left ventricular contractility was assessed by pressure-area relations using echocardiographic automated border detection during inflow occlusion before and after cardiopulmonary bypass. Linear regression analysis in 16 patients with paired data sets assessed changes in contractility. RESULTS: The relation was highly linear (r = 0.95+/-0.02). A change of slope versus the change in x intercept was detected in controls (mean difference, 16.1 mm Hg/cm2, 95% confidence limits, 5.9 to 26.3; 2.2 cm2, 95% confidence limits, -1.1 to 5.5; p = 0.007), which was different from those of treated patients (mean difference, 0.7 mm Hg/cm2, 95% confidence limits, -2.2 to 3.7; -0.06 cm2, 95% confidence limits, -1.6 to 1.5; p > 0.2). Analysis of covariance in the overall group confirmed a significant effect of treatment (p = 0.002). CONCLUSIONS: Enflurane enhances postischemic functional recovery, possibly through pharmacologic preconditioning of myocardium.

Effects of inhalation and intravenous anesthetic agents on pressor response to NG-nitro-L-arginine.

The effects of anaesthetic agents on pressor effect of NG-nitro-L-arginine (L-NNA), a potent inhibitor of nitric oxide (NO) synthesis, were examined in rats. I.v. bolus of L-NNA (1-32 mg/kg) in conscious rats dose dependently increased mean arterial pressure (MAP) to a maximum value of 53 +/- 2 mmHg at 16 mg/kg with ED50 value of 4.7 +/- 0.9 mg/kg. The effects of a single i.v. bolus dose (32 mg/kg) of L-NNA were examined in conscious rats and rats anaesthetised with pentobarbital, chloralose, ketamine, althesin (mixture of alphaxalone and alphadolone), urethane, enflurane or halothane. In conscious rats, peak MAP (51 +/- 3 mmHg) was reached 10 min after i.v. injection and the effect lasted more than two hours. The magnitudes of peak MAP differed under the influence of anaesthetic agents with the following rank order: althesin greater than conscious = pentobarbital = chloralose = ketamine = urethane greater than enflurane much greater than halothane (in which there was negligible change in MAP). The onsets were delayed in rats anaesthetised with pentobarbital, althesin, chloralose and enflurane but not altered with ketamine and urethane compared to that in conscious rats. Therefore, L-NNA caused intense and prolonged pressor response in conscious rats and rats anaesthetised with the i.v. anaesthetic agents pentobarbital, chloralose, ketamine, althesin and urethane. MAP effect of L-NNA was markedly attenuated by the inhalation anaesthetics halothane and enflurane.

Nalbuphine: a supplement to isoflurane and enflurane anaesthesia.

A retrospective study was carried out to review the intra-operative use of nalbuphine at the average dose of 1.5 mg/kg as a supplement to isoflurane and enflurane in balanced anaesthesia in 108 surgical patients. Intra-operative cardiovascular stability and the quality of emergence were examined. The amount of halogenated anaesthetic used was compared to the theoretical amount that would have been needed in the absence of nalbuphine. In 90% to 95% of patients, blood pressures remained within 20% of baseline for the duration of anaesthesia. At emergence, 80% of patients had no pain. Nalbuphine appeared to reduce halogenated anaesthetic requirements by approximately 50%. These promising results for the intraoperative use of nalbuphine need to be confirmed by controlled prospective studies.

Study of biodistribution of enflurane in rats with in vivo 19F MRI.

In vivo 19F magnetic resonance imaging (MRI) of anesthetized rats enabled us to visualize the biodistribution of fluorinated anesthetics and to document the changes in MR signals in the body during the induction and the elimination phase of anesthesia. The authors examined in vivo 19F MRI in rats anesthetized with concentrations of 1.75-2.0% enflurane and demonstrated its in vivo distribution with concomitant 1H and 13C MRI to verify the anatomical correlation. Distinct 19F MR signals were acquired predominantly from the systemic adipose tissue and the liver. Additionally, the temporal changes in the tissue during and after anesthesia were characterized with in vivo 19F MRI in 6.4 min of the acquisition time. The 19F MR signals increased with time after anesthesia; however, the signals from the adipose tissue were apparently stronger than those from the liver. Following the discontinuation of inhalation, the MR signals in the liver decreased far more rapidly than those from the adipose tissue. When the animal woke up and began to move, the MR signals were still visible in the adipose tissue. These results confirmed the fact that enflurane dissolves preferentially in the adipose tissue and remains when the anesthetic effect disappears. Additionally, 19F MR signals of the liver during the elimination phase might reflect the concentration of enflurane in the blood.

Cardiovascular and renal effects of enflurane and halothane in the dog.

A comparison between the effects of increasing concentrations of enflurane and halothane on cardiovascular and renal function in the artificially ventilated dog showed that both agents produced myocardial depression which was directly related to the concentration administered. Depression was more marked, and occurred at a lower minimum alveolar concentration (MAC) value with enflurane. No significant difference was found between the effects of the two agents on renal blood flow, glomerular filtration rate, renal vascular resistance or urine production at anaesthetic concentrations of 1 MAC. However, there was evidence of sudden depression of renal function as concentrations of enflurane were raised above 1 MAC, but with halothane a similar deterioration did not appear until the concentration of the inhalational agent reached 2 MAC.

The influence of anesthetic concentrations of enflurane and ethanol on caffeine metabolism in mice.

Enflurane is a fluorinated volatile anesthetic, mostly eliminated unchanged in exhaled air. About 10% of inhaled enflurane undergoes oxidative metabolism in liver via mixed function oxidase. We examined the influence of ethanol and subchronical exposition (6 hours a day, during five consecutive days) to subanesthetic and anesthetic concentrations of enflurane on liver function in BALB/c mice. Specially designed chamber for inhalatory application of anesthetics was constructed for this study. Animals were divided in six groups of twenty. The ethanol treated group was injected with ethanol intraperitoneally (1 g/kg). Two enflurane treated groups were intraperitoneally injected with 0.9% solution of sodium chloride (10 ml/kg) and one of them exposed to subanesthetic (0.5 Vol%) and the other one to anesthetic (2.75 Vol%) concentrations of enflurane. Following two groups received ethanol (1 g/kg) and each of them inhaled enflurane at previously mentioned doses. The control group was intraperitoneally injected with 0.9 % solution of sodium chloride (10 ml/kg) and did not receive any anesthetic. On the day following the last day of exposure half of the animals from each group were sacrificed for determination of glucose levels, erythrocyte glutathion levels, haematocrit, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), liver protein and glutathion levels, and total cytochrome P-450 (CYP P-450). The other half of animals from each group were injected intraperitoneally with caffeine (20 mg/kg). Caffeine and its metabolites in 8 hour urine were analyzed by high performance liquid chromatography (HPLC) method. Excretion of caffeine and its metabolites was different among the groups. We followed two caffeine metabolic ratios - 1,3-dimethyl uric acid and 3,7-xanthine (1,3-U/3,7-X) and 3,7-dimethyl xanthine + 7-xanthine and 1-xanthine + 1,7-dimethyl uric acid (3,7-X + 7-X/1-X + 1,7-U). The difference in caffeine metabolites ratios suggests that enflurane changes oxidative metabolism in liver via certain subtypes of mixed function oxidase, probably via CYP-4502E1. This effect is more expressed when ethanol and enflurane are applied together. Ethanol is well known inductor of CYP-4502E1 and the registrated enzyme induction could be explained by both influences - of ethanol and enflurane.

Enflurane, halothane, and isoflurane potency in horses.

The minimal alveolar concentration of anesthetic required to prevent gross purposeful movement in response to electrical stimulation of oral mucous membranes was determined in horses for 3 agents. Equipotent concentrations of enflurane were 2.12 volumes %; of halothane, 0.88 volumes %; and of isoflurane, 1.31 volumes +. The alveolar concentration required to produce at least 60 seconds of apnea was also determined for these agents. From these data and the minimal alveolar concentration information, anesthetic indices were determined for each agent. The indices for enflurane, halothane, and isoflurane were 2.26, 2.60, and 2.33, respectively.

Potency of enflurane in dogs: comparison with halothane and isoflurane.

Circulatory and respiratory responses to graded increases in alveolar concentrations of enflurane were investigated in unpremedicated healthy dogs during conditions of spontaneous and controlled ventilation. The minimal alveolar concentration (MAC) of enflurane that prevented movement in response to a standard painful stimulus was determined for each dog and averaged 2.06 vol%. In these studies, enflurane produced cardiopulmonary depression in proportion to the alveolar dose. The average end-tidal enflurane concentration that produced at least 60 s of apnea was 5.29 vol% (ie, MAC 2.57). A comparison of these data with previous studies in dogs indicates that equipotent concentrations of enflurane are at least as depressant to the cardiopulmonary system as halothane and isoflurane.

Fatal recreational inhalation of enflurane.

We report here a case of fatal enflurane poisoning by recreational inhalation, apparently the first published report of such a case.