High Concentrations Of Isoflurane Research Articles

Comparison of 2 anesthetic protocols and surgical timing during cesarean section on neonatal vitality and umbilical cord blood parameters

BackgroundThe objective of this study was to evaluate the relationship between the mode of anesthesia, the time form the induction to the extraction of a puppy and the immediate postnatal vitality and umbilical cord blood gases parameters in cesarean section derived-puppies. Two different anesthetic protocols were used: inhalation using isoflurane (ISO) and combined—inhalation and epidural (EPI) with propofol being the induction agent.ResultsSignificant differences were found in ISO group in pH values, pCO2 levels and Apgar scores between puppies at different extraction times (< 30 vs. ≥ 30 min). In ISO group puppies extracted later were more acidic (7.16 vs. 7.22), had higher levels of pCO2 (69 vs. 57 mmHg) and lower Apgar scores at birth (1.2 vs. 2.5). On the contrary, in EPI group no differences were observed between the delivery time, umbilical blood gas parameters and puppies’ vitality. Furthermore, the dams from the EPI group required lower concentrations of isoflurane (MAC 1.11 ± 0.19 vs.1.37 ± 0.16, p < 0.001).ConclusionsMultiple pregnancies frequent in dogs lead to significant differences in extraction times between the first and the last puppy during cesarean section. Obtained results showed that the mode of anesthesia and the surgical time would influence the neonatal outcome during cesarean section in dogs. The higher concentration of isoflurane with the longer time of exposure had a negative effect on the initial newborn vitality as well as the umbilical cord blood gas parameters. Therefore, when performing CS in giant dog breeds or expecting many puppies in the litter, it is worth considering epidural component that allow for lower concentrations of inhalant agents, which may contribute to a better clinical condition of newborns.

Anaesthetic management of 10 horses undergoing cervical intervertebral body fusion ‘wobbler surgery’

AbstractSurgical techniques for cervical intervertebral body fusion ‘wobbler surgery’ are frequently reported in the literature, but the anaesthetic management is rarely described. Considering the invasive and complex nature of the surgical procedure, prolonged anaesthetic duration and potential for pre‐existing and post‐operative neurological deficits, the anaesthetic and analgesic approach poses specific challenges. This article aims to discuss the anaesthetic management, intra‐operative complications and recovery experience in 10 horses undergoing surgical treatment of cervical spinal cord compression. The four types of intra‐operative complication encountered generally responded well to first‐line treatment. All horses recovered successfully, and recovery quality, in most cases, was good despite the presence of several factors known to adversely affect recovery quality. However, the need for additional intra‐operative ketamine and relatively high isoflurane concentrations to obtain an adequate anaesthetic depth despite provision of partial intravenous anaesthesia and multi‐modal analgesia indicates that further analgesic techniques may be warranted.

Beclin1-mediated ferroptosis activation is associated with isoflurane-induced toxicity in SH-SY5Y neuroblastoma cells.

The widely used inhalation anesthetic, isoflurane, potentially induces neuronal injury in clinical practice. Previous studies showed multiple forms of cell death that resulted from isoflurane-induced cytotoxicity, but the precise underlying mechanism remains poorly understood. Ferroptosis has recently been identified as a non-apoptotic form of regulated cell death. Here, we found that ferroptosis inhibitors, ferrostatin-1 and deferoxamine mesylate (DFOM), showed great efficiency in maintaining cell viability in SH-SY5Y neuroblastoma cells exposed to a high concentration of isoflurane for 24h. We also observed that cellular chelatable iron and lipid peroxidation were increased in a concentration-dependent manner in response to isoflurane. In addition, isoflurane upregulated Beclin1 phosphorylation, followed by the formation of a Beclin1-solute carrier family 7 member 11 (SLC7A11) complex, which affected the activity of cystine/glutamate antipoter and further regulated ferroptotic cell death. Accordingly, Beclin1 overexpression aggravated isoflurane-induced cell damage by upregulating ferroptosis. This phenomenon was significantly attenuated by silencing of Beclin1 in SH-SY5Y cells. These findings indicate that Beclin1 may regulate ferroptosis in a manner involving inhibition of glutamate exchange activity of system xc(-), which is implicated in isoflurane-induced toxicity. In particular, when isoflurane is administrated at high concentrations and for an extended duration, ferroptosis is more likely to play a crucial role in isoflurane-induced toxicity.

Inhalative sedation with small tidal volumes under venovenous ECMO.

Inhalative sedation is an emerging method for long-term sedation in intensive care therapy. There is evidence that it is easy to control and may be beneficial compared to intravenous sedation. Yet little is known about the use in patients with compromised lung function. In this retrospective analysis, we searched files of patients receiving inhalative sedation under venovenous extracorporeal membrane oxygenator (vv-ECMO) support due to lung failure. After ethical approval, we performed a retrospective analysis of patients receiving vv-ECMO support and inhalative sedation in the surgical ICU in 2015. Isoflurane was administered via the AnaConDa®-system. Sedation was tested using Richmond Agitation and Sedation scale (RASS). 7 patients were identified. Median age was 50years (26/70years). All were male. Median ECMO runtime was 129h (37/1008h) and the survival rate was 57.9%. Dose of isoflurane was 1.7ml/h (0.8 / 4.0ml/h) resulting in expiratory concentrations of 0.8 Vol% (0.3/1.8 Vol%), inspiratory of 0.6 Vol% (0.1/1.4 Vol%). Higher concentrations of isoflurane were associated with increased depth of sedation (expiratory p = 0.016; inspiratory p = 0.027; averaged p = 0.015). With tidal volume below 350ml, association was still present for expiratory and averaged concentrations of isoflurane (expiratory p = 0.031; inspiratory p = 0.082; average p = 0.039). This is the first study that shows that inhalative concentrations of isoflurane are associated with depth of sedation in patients with lung failure. We were able to show that even with major impacts in lung mechanics and function targeted sedation with volatile anaesthetics is feasible and dose-response relationship appears to exist.

Assessing the influence of isoflurane anesthesia on cardiac metabolism using hyperpolarized [1-13 C]pyruvate.

Isoflurane is a frequently used anesthetic in small-animal dissolution dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) studies. Although the literature suggests interactions with mitochondrial metabolism, the influence of the compound on cardiac metabolism has not been assessed systematically to date. In the present study, the impact of low versus high isoflurane concentration was examined in a crossover experiment in healthy rats. The results revealed that cardiac metabolism is modulated by isoflurane concentration, showing increased [1-13 C]lactate and reduced [13 C]bicarbonate production during high isoflurane relative to low isoflurane dose [average differences: +16% [1-13 C]lactate/total myocardial carbon, -22% [13 C]bicarbonate/total myocardial carbon; +51% [1-13 C]lactate/[13 C]bicarbonate]. These findings emphasize that reproducible anesthesia is important when studying cardiac metabolism. As the depth of anesthesia is difficult to control in an experimental animal setting, careful study design is required to exclude confounding factors.

The relationship between intestinal and oral mucosa microcirculation in anaesthetized horses

ObjectiveTo compare alteration in intestinal blood flow in anaesthetized horses with changes in oral mucosa blood flow. Study designProspective, randomized clinical study. AnimalsEight warmblood horses. MethodsAfter induction with guaifenesin and ketamine, anaesthesia was maintained with isoflurane at 1.5 vol% in oxygen. The tissue blood flow was measured using laser Doppler flowmetry at the jejunum, colon, rectal mucosa, oesophageal mucosa and the oral mucosa. After three baseline measurements, blood flow was first increased by dobutamine infusion and thereafter decreased by increasing isoflurane concentration and all measurements repeated twice. anova was used for comparing the measured parameters to baseline and correlation between the different measurement localizations was examined using Pearson correlation (p < 0.05). ResultsMicroperfusion at all measurement sites increased significantly during dobutamine infusion and decreased significantly during high isoflurane concentration. There was a significant correlation between flow at the oral mucosa and flow at the jejunum (r2 = 0.77, p = 0.002), colon (r2 = 0.76, p < 0.001), rectal mucosa (r2 = 0.88, p < 0.001) and oesophageal mucosa (r2 = 0.83, p <0.001). Conclusions and clinical relevanceOral mucosa blood flow can be used in isoflurane anaesthetized horses to reflect changes of intestinal microcirculation.

Differential Suppression of Spontaneous and Noxious-evoked Somatosensory Cortical Activity by Isoflurane in the Neonatal Rat.

The effect of neonatal anesthesia and pain on the developing brain is of considerable clinical importance, but few studies have evaluated noxious surgical input to the infant brain under anesthesia. Herein, the authors tested the effect of increasing isoflurane concentration on spontaneous and evoked nociceptive activity in the somatosensory cortex of rats at different postnatal ages. Intracortical extracellular field potentials evoked by hind paw C-fiber electrical stimulation were recorded in the rat somatosensory cortex at postnatal day (P) 7, P14, P21, and P30 during isoflurane anesthesia (n = 7 per group). The amplitudes of evoked potentials and the energies of evoked oscillations (1 to 100 Hz over 3 s) were measured after equilibration at 1.5% isoflurane and during step increases in inspired isoflurane. Responses during and after plantar hind paw incision were compared at P7 and P30 (n = 6 per group). At P7, cortical activity was silent at 1.5% isoflurane but noxious-evoked potentials decreased only gradually in amplitude and energy with step increases in isoflurane. The resistance of noxious-evoked potentials to isoflurane at P7 was significantly enhanced after surgical hind paw incision (69 ± 16% vs. 6 ± 1% in nonincised animals at maximum inspired isoflurane). This resistance was age dependent; at P14 to P30, noxious-evoked responses decreased sharply with increasing isoflurane (step 3 [4%] P7: 50 ± 9%, P30: 4 ± 1% of baseline). Hind paw incision at P30 sensitized noxious-evoked potentials, but this was suppressed by higher isoflurane concentrations. Despite suppression of spontaneous activity, cortical-evoked potentials are more resistant to isoflurane in young rats and are further sensitized by surgical injury.

Repeated isoflurane exposure and neuroapoptosis in the midgestation fetal sheep brain

Advances in surgery and technology have resulted in increased in-utero procedures. However, the effect of anesthesia on the fetal brain is not fully known. The inhalational anesthetic agent, isoflurane, other gamma amino butyric acid agonists (benzodiazepines, barbiturates, propofol, other inhalation anesthetics), and N-methyl D aspartate antagonists, eg, ketamine, have been shown to induce neuroapoptosis. The ovine model has been used extensively to study maternal-fetal physiologic interactions and to investigate different surgical interventions on the fetus. The purpose of this study was to determine effects of different doses and duration of isoflurane on neuroapoptosis in midgestation fetal sheep. We hypothesized that repeated anesthetic exposure and high concentrations of isoflurane would result in increased neuroapoptosis. Time-dated, pregnant sheep at 70 days gestation (term 145 days) received either isoflurane 2% × 1 hour, 4% × 3 hours, or 2% × 1 hour every other day for 3 exposures (repeated exposure group). Euthanasia occurred following anesthetic exposure and fetal brains were processed. Neuroapoptosis was detected by immunohistochemistry using anticaspase-3 antibodies. Fetuses unexposed to anesthesia served as controls. Another midgestation group with repeated 2% isoflurane exposure was examined at day 130 (long-term group) and neuronal cell density compared to age-matched controls. Representative sections of the brain were analyzed using Aperio Digital imaging (Leica Microsystems Inc, Buffalo Grove, IL). Data, reported by number of neurons per cubic millimeter of brain tissue are presented as means and SEM. Data were analyzed using the Mann-Whitney U and Kruskal-Wallis tests as appropriate. A total of 34 fetuses were studied. There was no significant difference in neuroapoptosis observed in fetuses exposed to 2% isoflurane for 1 hour or 4% isoflurane for 3 hours. Increased neuroapoptosis was observed in the frontal cortex following repeated 2% isoflurane exposure compared to controls (1.57 ± 0.22 × 10(6)/mm(3) vs 1.01 ± 0.44 × 10(6)/mm(3), P = .02). Fetuses at 70 days gestation with repeated exposure demonstrated decreased frontal cortex neurons at day 130 when compared to age-matched controls (2.42 ± 0.3 × 10(5)/mm(3) vs 7.32 ± 0.4 × 10(5)/mm(3), P = .02). No significant difference in neuroapoptosis was observed between the repeated exposure group and controls in the hippocampus, cerebellum, or basal ganglia. Repeated isoflurane exposure in midgestation sheep resulted in increased frontal cortex neuroapoptosis. This persisted into late gestation as decreased neuronal cell density. While animal studies should be extrapolated to human beings with caution, our findings suggest that the number of anesthetic/sedative exposures should be considered when contemplating the risks and benefits of fetal intervention as certain fetal therapies may need to be repeated.

In Vitro Induction of Endothelial Apoptosis of the Post-Hypoxic Blood-Brain Barrier by Isoflurane but Not by Sevoflurane and Midazolam.

BackgroundThe effects of anesthetics on the injured brain continue to be the subject of controversial discussion. Since isoflurane has recently been shown to induce apoptosis of cerebral endothelial cells, this study compared different anesthetic compounds regarding their potential to induce cerebro-vascular apoptosis.MethodsThe in vitro model of the blood-brain barrier used in this study consisted of astrocyte-conditioned human umbilical vein endothelial cells (AC-HUVEC) has been used. After 24 h of deep hypoxia and reoxygenation or control treatment, AC-HUVEC were exposed to 0, 0.5, 1.0, or 2.0 times the minimum alveolar concentration of isoflurane or sevoflurane, or 0, 75, 150, or 300 nM of midazolam for 2 h. After 24 h, AC-HUVEC were harvested, and the degree of apoptosis was assessed by means of Western blots for the Bax and Bcl-2 ratio and, for controls and the highest concentration groups, terminal deoxynucleotidyl-mediated dUTP-biotin nick end labeling (TUNEL).ResultsWithout hypoxic pretreatment, 2.0 MAC of isoflurane slightly increased TUNEL intensity compared to control and sevoflurane, but without any significant changes in the Bax and Bcl-2 ratio. After hypoxic pretreatment, exposure to isoflurane led to a multifold increase in the Bax and Bcl-2 ratio in a dose dependent manner, which was also significantly higher than the ratio observed in the 2 MAC sevoflurane group. TUNEL intensity in the post-hypoxic 2 MAC isoflurane group was increased by a factor of 11 vs. control and by 40 vs. sevoflurane. Sevoflurane and midazolam did not significantly alter these markers of apoptosis, when compared to the control group.ConclusionsIsoflurane administered after hypoxia elevates markers of apoptosis in endothelial cells transdifferentiated to the cerebro-vascular endothelium. Endothelial apoptosis may be a previously underestimated mechanism of anesthetic neurotoxicity. Administration of high concentrations of isoflurane in experimental settings may have negative effects on the blood-brain barrier.

Effects of isoflurane anesthesia on F‐waves in the sciatic nerve of the adult rat

Nerve conduction studies provide insights into the functional consequences of axonal and myelin pathology in peripheral neuropathies. We investigated whether isoflurane inhalation anesthesia alters F-wave latencies and F-persistence in the sciatic nerve of adult rats. Ten rats were investigated at 3 different isoflurane concentrations followed by ketamine-xylazine injection anesthesia. To assess F-wave latencies, a stimulation paradigm was chosen to minimize H-reflex masking of F-waves. F-wave persistence rates were reduced with 3.5% isoflurane concentration at 4 and 10 Hz supramaximal stimulation and marginally reduced with 2.5% isoflurane when compared with ketamine-xylazine. F-wave amplitudes decreased progressively with rising stimulus frequency in all types of anesthesia and most at 3.5% isoflurane concentration. The type of anesthesia and the stimulus repetition rate have an impact on some F-wave parameters. Higher isoflurane concentrations and repetition rates are not recommended in experimental studies using rat neuropathy models where F-waves are of interest.

Effect of high dose isoflurane on cerebral blood flow in macaque monkeys

The effect of high dose isoflurane on cerebral blood flow (CBF) was investigated in adult macaque monkeys receiving 1% to 2% isoflurane with the pseudo continuous arterial-spin-labeling (pCASL) MRI technique. High concentration (2%) of isoflurane resulted in significant increase in the mean CBF of the global, cortical, subcortical regions and the regional CBF in all subcortical structures and most cortical structures (such as motor cortex, anterior cingulate cortex, but not media prefrontal cortex). In addition, the changes of regional CBF in the affected regions correlated linearly with increasing isoflurane concentrations. The study demonstrates region-specific CBF abnormal increase in adult macaque monkeys under high dose (2%) isoflurane and suggests that the brain functionality in the corresponding structures may be affected and need to be taken consideration in either human or non-human primate neuroimaging studies.

Combined spinal and general anesthesia is better than general anesthesia alone for laparoscopic hysterectomy.

Context:Spinal anesthesia (SA) was combined with general anesthesia (GA) for achieving hemodynamic stability in laparoscopic hysterectomy.Aims:The aim of our study was to evaluate the impact of SA combined with GA in maintaining hemodynamic stability in laparoscopic hysterectomy. The secondary outcomes studied were requirement of inhaled anesthetics, vasodilators, and recovery profile.Settings and Design:We conducted a prospective, randomized study in ASAI/II patients posted for laparoscopic hysterectomy, who were willing to participate in the study.Materials and Methods:Patients were randomly assigned to receive SA with GA (group SGA) or plain GA (group GA). Group SGA received 10 mg bupivacaine (heavy) for SA. GA was administered using conventional balanced technique. Maintenance was carried out with nitrous oxide, oxygen, and isoflurane. Comparison of hemodynamic parameters was carried out during creation of pneumoperitoneum and thereafter. Total isoflurane requirement, need of vasodilators, recovery profile, and regression of SA were studied.Statistical analysis used:Descriptive statistics in the form of mean, standard deviation, frequency, and percentages were calculated for interval and categorical variables, respectively. One-way analysis of variance (ANOVA) was applied for noting significant difference between the two groups, with chi-square tests for categorical variables and post-hoc Bonferroni test for interval variables. Comparison of heart rate (HR), mean arterial pressure (MAP), SPO2, and etCO2 was done with Student's t-test or Mann–Whitney test, wherever applicable.Results:Patients in group SGA maintained stable and acceptable MAP values throughout pneumoperitoneum. The difference as compared to group GA was statistically significant (P < 0.01). Group GA showed additional requirement of metoprolol (53.33%) and higher concentration of isoflurane (P < 0.001) to combat the increased MAP. Recovery was early and quick in group SGA as against group GA (P = 0.000). There were no adverse/residual effects of SA.Conclusion:The hemodynamic repercussions during pneumoperitoneum can be effectively attenuated by combining SA and GA, without any adverse effects.

Echocardiographic assessment of β-adrenoceptor stimulation-induced heart failure with reduced heart rate in mice

1. Chronic injection with the β-adrenoceptor (β-AR) agonist isoproterenol (ISO) has been commonly used as an animal model of β-AR-induced cardiac remodelling and heart failure. This ISO-treated model usually exhibits significantly decreased conscious heart rate (HR). However, the HR in treatment groups is usually adjusted to the same levels by anaesthesia to assess cardiac geometry and function. In the present study, we report a method of echocardiographic assessment that represents the true cardiac geometry and function under conditions of ISO withdrawal. 2. Briefly, C57BL/6 mice were treated with 5 mg/kg per day ISO for 12 weeks. Cardiac geometry and function were assessed by high-resolution echocardiography in vehicle (saline) - and ISO-treated mice that were either conscious or anaesthetized using different concentrations of isoflurane. 3. The cardiac β-AR response was decreased in ISO-treated mice, as evidenced by markedly decreased conscious HR. Vehicle- and ISO-treated mice did not differ in terms of cardiac geometry or function when HR was adjusted to the same level (400 b.p.m.) in both treatment groups, but cardiac geometry and function did differ when a low (1%) rather than high (1.5% or 2%) isoflurane concentration was used to adjust HR. Furthermore, 3 day ISO withdrawal eliminated the difference in conscious HR between the two groups. In addition, the groups differed in cardiac geometry and function regardless of the isoflurane concentration used. 4. In conclusion, using isoflurane to decrease the HR of treated groups to the same level may mask left ventricular dysfunction in ISO-treated mice. Withdrawal of ISO eliminated the difference in basal HR between the ISO-treated and control groups on echocardiography, allowing a more accurate assessment of cardiac pathological and functional changes.

Cardiopulmonary effects of three concentrations of isoflurane with or without mechanical ventilation and supramaximal noxious stimulation in New Zealand white rabbits

To determine the cardiopulmonary effects of 3 doses of isoflurane, with and without controlled mechanical ventilation and noxious stimulation, in healthy adult New Zealand white rabbits. 6 adult female rabbits. Each rabbit was administered isoflurane in oxygen at each of 3 anesthetic doses (1.0, 1.5, or 2.0 times the published minimum alveolar concentration of 2.07%). At each anesthetic dose, blood gas and cardiopulmonary measurements were obtained before and during application of a supramaximal noxious stimulus. Effects of spontaneous and mechanical ventilation were assessed during separate anesthetic episodes. Mean ± SEM isoflurane concentrations used were 2.11 ± 0.04%, 3.14 ± 0.07%, and 4.15 ± 0.06%. During spontaneous ventilation, the rabbits' Paco2 and mixed venous Pco2 significantly increased with concomitant reductions in both arterial and mixed venous pH as isoflurane concentration increased. Cardiac output and vascular resistance did not change significantly. Noxious stimulation minimally affected measured cardiopulmonary variables. During mechanical ventilation, significant reductions in arterial blood pressures and cardiac output occurred with increasing isoflurane dose. Systemic vascular resistance index at the highest anesthetic dose was significantly lower than the value at the lowest anesthetic dose. During noxious stimulation, systolic arterial blood pressure and cardiac output significantly increased at the 2 lower isoflurane concentrations, but not at the highest concentration. In rabbits, isoflurane-induced dose-dependent cardiopulmonary depression was attributable to vasodilation and negative inotropy. At an isoflurane concentration of 4.15% with mechanical ventilation, cardiovascular depression was severe; use of unnecessarily high isoflurane concentrations in this species should be avoided.

Effects of different doses of propofol or isoflurane on cochlear blood flow in guinea pigs

Objective To evaluate the effects of different doses of propofol or isoflurane on the cochlear blood flow (CBF) in guinea pigs.Methods Fifty-four adult male guinea pigs,aged 3 months,weighing 400-500 g,were randomly divided into 6 groups (n =9 each).In P1,P2 and P3 groups,propofol was infused for 115 min at 10,20 and 40 mg· kg-1 · h-1,respectively,after a loading dose of 5 mg/kg was injected over 5 min.In S1,S2 and S3 groups,isoflurane was inhaled for 120 min with end-tidal concentrations of 1％,2％ and 3 ％,respectively.Mean arterial pressure and CBF were recorded before administration (baseline,T1) and during the period of drug administration.Distortion product otoacoustic emission (DPOAE) was measured at T1,at the end of administration (T2) and 1 h after administration (T3).Five animals in each group were sacrificed and organs of Corti were harvested for observation of morphology of out hair cells by scanning electron microscopy.Results Propofol decreased MAP and increased CBF and DPOAE amplitude in a dose-dependent manner.Isoflurane decreased MAP and CBF in a dose-dependent manner.1％ isoflurane increased DPOAE amplitude,however,2％ and 3％ isoflurane decreased it and caused damage to out hair cells.Conclusion Propofol induces an increase in CBF in guinea pigs,while high concentration of isoflurane induces a decrease in CBF.Isoflurane inhibits CBF autoregulation,which makes CBF more sensitive to perfusion pressure,thus causing damage to hearing function.This is the reason why high concentration of isoflurane induces a decrease in CBF. Key words: Propofol ; Isoflurane ; Cochlea ; Regional blood flow ; Auditory perception

Dual Effects of Isoflurane on Neuronal Proliferation/Differentiation

Dual Effects of Isoflurane on Neuronal Proliferation/Differentiation

Dose-dependent effect of isoflurane on regional cerebral blood flow in anesthetized macaque monkeys

The dose-dependent effect of isoflurane on regional CBF of cortical and subcortical structures in anesthetized macaque monkeys was investigated with the Continuous ASL MRI technique. High concentration of isoflurane resulted in global CBF increase and blood pressure decrease. Evident CBF change was observed in the subcortical structures. Specifically, CBF in thalamus and cerebellum was increased about 39% and 55% when isoflurane concentration was changed from 0.75% to 1.5%, respectively. Also, those regional CBF changes correlated linearly with isoflurane inspiratory concentrations, indicating impaired CBF autoregulation in these structures. In contrast, no obvious CBF changes were observed in anterior cingulated cortex, motor cortex, medial prefrontal cortex, and caudate. The results demonstrate that, under the 0.75–1.5% isoflurane maintenance doses, the CBF auto-regulation is well preserved in the cerebral cortical regions and caudate, but impaired in thalamus and cerebellum, indicating disturbed CBF-metabolism coupling and functional response in specific subcortical regions of anesthetized macaque monkeys.

Einsatz von Atracurium bei der Vitrektomie des Pferdes

In most ocular procedures, a central position of the eye is necessary. This can be achieved using a deep plane of anaesthesia, locoregional blocks or with neuromuscular blocking agents. The aim of this study was to evaluate the influence of atracurium on cardiovascular parameters, and on recovery quality and duration in horses. Thirty-four warmblood horses undergoing in total 50 vitrectomies were divided into two groups. Premedication, induction and maintenance were identical in all patients. After 20 minutes, horses of group A received atracurium (0.1 mg/kg) while in the control group (group K) the depth of anaesthesia was adapted to keep the bulbus in a central position. Dobutamine and fluids were administered to maintain the mean arterial blood pressure (MAP) above 70 mmHg. Cardiac output (CO), heart rate (HR), MAP, respiratory rate, end-expiratory isoflurane concentration (ETIso) and dobutamine requirements were determined. Position and movement of the globe during the surgical procedure were scored. Time and quality of the recovery period was scored. Horses of group K required significantly higher concentrations of isoflurane (group A: 1.08 ± 0.1%; group K: 1.34 ± 0.2%) and had an overall lower MAP (group A: 88.4 ± 10.3 mmHg; group K: 76.6 ± 11.6 mmHg) and CO (group A: 36.9 ± 11.7 l/min; group K: 28.5 ± 7.2 l/min) but needed significantly more dobutamine (group A: 0.37 ± 0.17 μg/kg/min; group K: 0.99 ± 0.46 μg/kg/min) compared to group A. Complete relaxation occurred 9.5 ± 2.5 minutes after atracurium bolus and lasted for 25 ± 7.1 minutes. The score of the bulbus position and movement was significantly lower in group A, resulting in a better quality for the surgical procedure. In group A, the recovery time to standing was significantly shorter (group A: 18.1 ± 5.4 min; group K: 31.5 ± 7.1 min), with no difference in quality. The use of atracurium resulted in a better cardiovascular condition, probably because of the isoflurane-sparing effect. The recovery time was shorter in these horses without negative effects on recovery quality. No signs of residual atracurium effects were detected.

Fetal exposure to high isoflurane concentration induces postnatal memory and learning deficits in rats

We developed a maternal fetal rat model to study the effects of isoflurane-induced neurotoxicity on the fetuses of pregnant rats exposed in utero. Pregnant rats at gestational day 14 were exposed to 1.3 or 3% isoflurane for 1h. At postnatal day 28, spatial learning and memory of the offspring were examined using the Morris Water Maze. The apoptosis was evaluated by caspase-3 immunohistochemistry in the hippocampal CA1 region. Simultaneously, the ultrastructure changes of synapse in the hippocampal CA1 and dentate gyrus region were observed by transmission electron microscopy (TEM). The 3% isoflurane treatment group showed significantly longer escape latency, less time spent in the third quadrant and fewer original platform crossings in the Morris Water Maze test, significantly increased number and optical densities of caspase-3 neurons. This treatment also produced remarkable changes in synaptic ultrastructure compared with the control and the 1.3% isoflurane groups. There were no differences in the Morris Water Maze test, densities of caspase-3 positive cells, or synaptic ultrastructure between the control and 1.3% isoflurane groups. High isoflurane concentration (3%) exposure during pregnancy caused spatial memory and learning impairments and more neurodegeneration in the offspring rats compared with control or lower isoflurane concentrations.

Suppression of Ischemic and Reperfusion Ventricular Arrhythmias by Inhalational Anesthetic-Induced Preconditioning in the Rat Heart

Inhalational anesthetic-induced preconditioning (APC) has been shown to reduce infarct size and attenuate contractile dysfunction caused by myocardial ischemia. Only a few studies have reported the effects of APC on arrhythmias during myocardial ischemia-reperfusion injury, focusing exclusively on reperfusion. Accordingly, the aim of the present study was to examine the influence of APC on ventricular arrhythmias evoked by regional no-flow ischemia. APC was induced in adult male Wistar rats by 12-min exposures to two different concentrations (0.5 and 1.0 MAC) of isoflurane followed by 30-min wash-out periods. Ventricular arrhythmias were assessed in the isolated perfused hearts during a 45-min regional ischemia and a subsequent 15-min reperfusion. Myocardial infarct size was determined after an additional 45 min of reperfusion. The incidence, severity and duration of ventricular arrhythmias during ischemia were markedly reduced by APC. The higher concentration of isoflurane had a larger effect on the incidence of ventricular fibrillation than the lower concentration. The incidence of ventricular tachycardia and reversible ventricular fibrillation during reperfusion was also significantly reduced by APC; the same was true for myocardial infarct size. In conclusion, we have shown that preconditioning with isoflurane confers profound protection against myocardial ischemia- and reperfusion-induced arrhythmias and lethal myocardial injury.