Deep Isoflurane Anesthesia Research Articles

Deep isoflurane anesthesia is associated with alterations in ion homeostasis and specific Na+/K+-ATPase impairment in the rat brain.

Maintenance of ion homeostasis is essential for normal brain function. Inhalational anesthetics are known to act on various receptors but their effects on ion homeostatic systems, such as the Na+/K+-ATPase, remain largely unexplored. Based on reports demonstrating global network activity and wakefulness modulation by interstitial ions, we hypothesized that deep isoflurane anesthesia affects ion homeostasis and the key mechanism for clearing extracellular K+, the Na+/K+-ATPase. Using ion-selective microelectrodes, we assessed isoflurane-induced extracellular ion dynamics in cortical slices of male and female Wistar rats in the absence of synaptic activity, the presence of two-pore-domain K+ channel antagonists, during seizures, and spreading depolarizations. We measured specific isoflurane effects on Na+/K+-ATPase function using a coupled enzyme assay and studied the relevance of our findings in vivo and in silico. Isoflurane concentrations clinically relevant for burst suppression anesthesia increased baseline [K+]o (mean±SD: 3.0 ± 0.0 versus 3.9 ± 0.5mM, p<0.001, n=39) and lowered [Na+]o (153.4 ± 0.8 versus 145.2 ± 6.0mM, p<0.001, n=28). Similar changes in [K+]o, [Na+]o, and a substantial drop in [Ca2+]o (1.5 ± 0.0 versus 1.2 ± 0.1mM, p=0.001, n=16) during inhibition of synaptic activity and two-pore-domain K+ suggested a different underlying mechanism. Following seizure-like events and spreading depolarization, isoflurane greatly slowed [K+]o clearance (63.4 ± 18.2 versus 196.2 ± 82.4s, p<0.001, n=14). Na+/K+-ATPase activity was markedly reduced after isoflurane exposure (>25%), affecting specifically the α2/3 activity fraction. In vivo, isoflurane-induced burst suppression resulted in impaired [K+]o clearance and interstitial K+ accumulation. A computational biophysical model reproduced the observed effects on [K+]o and displayed intensified bursting when Na+/K+-ATPase activity was reduced by 35%. Finally, Na+/K+-ATPase inhibition with ouabain induced burst-like activity during light anesthesia in vivo. Our results demonstrate cortical ion homeostasis perturbation and specific Na+/K+-ATPase impairment during deep isoflurane anesthesia. Slowed K+ clearance and extracellular accumulation might modulate cortical excitability during burst suppression generation while prolonged Na+/K+-ATPase impairment could contribute to neuronal dysfunction after deep anesthesia.

Neuroanatomical Basis for the Orexinergic Modulation of Anesthesia Arousal and Pain Control.

Hypothalamic orexin (hypocretin) neurons play crucial roles in arousal control. Their involvement in anesthesia and analgesia remains to be better understood. In order to enhance our view on the neuroanatomy, we systematically mapped the projections of orexin neurons with confocal microscope and light sheet microscope. We specifically expressed optogenetic opsins tagged with fluorescence markers in orexin neurons through adeno-associated viral infection in the mouse brain. The imaging results revealed fine details and novel features of the orexin projections throughout the brain, particularly related to the nuclei regulating arousal and pain. We then optogenetically activated orexin neurons in the lateral hypothalamus to study the effects on anesthesia-related behaviors. cFos staining showed that optogenetic stimulation can activate orexin neurons in the ChR2-mCherry group, but not the control mCherry group (62.86 ± 3.923% vs. 7.9 ± 2.072%; P < 0.0001). In behavior assays, optogenetic stimulation in the ChR2-mCherry group consistently elicited robust arousal from light isoflurane anesthesia (9.429 ± 3.804 s vs. 238.2 ± 17.42 s; P < 0.0001), shortened the emergence time after deep isoflurane anesthesia (109.5 ± 13.59 s vs. 213.8 ± 21.77 s; P = 0.0023), and increased the paw withdrawal latency in a hotplate test (11.45 ± 1.185 s vs. 8.767 ± 0.7775; P = 0.0317). The structural details of orexin fibers established the neuroanatomic basis for studying the role of orexin in anesthesia and analgesia.

Effects of riluzole on spinal seizure-like activity in the brainstem-spinal cord preparation of newborn rat

Riluzole blocks persistent Na+ current, inhibits generation of neuronal bursts and decreases glutamate-induced excitotoxicity. In previous studies of respiratory activity, riluzole suppressed inspiratory-related burst generation activity in rat slice or en bloc preparations. We examined riluzole’s effects on inspiratory burst generation and drug-induced seizure-like activity in newborn rat en bloc preparations. Medulla-spinal cord preparations from postnatal day 0–3 Wistar rats were isolated under deep isoflurane anesthesia and were superfused with artificial cerebrospinal fluid equilibrated with 95% O2 and 5% CO2, pH 7.4, at 25–26°C. Inspiratory activity was monitored from the fourth cervical ventral root. Seizure-like activity was induced by application of 20μM DL-threo-β-benzyloxyasparatate (TBOA, a glutamate uptake blocker preferentially acting on astrocytes) or coadministration of GABAA antagonist bicuculline (10μM) and glycine antagonist strychnine (10μM). Pretreatment and co-application with 10μM riluzole abolished the seizure-like burst activity induced by TBOA or bicuculline/strychnine. N-methyl-d-aspartic acid receptor antagonist MK801 (10μM) also depressed this activity. Riluzole may attenuate excessive glutamate action involved in pathological hyperexcitability of motor neurons with no major effect on generation of respiratory activity. Riluzole at the optimal dose could be a potential treatment to protect drug-induced epileptic brain tissue from excitotoxic damage without inducing respiratory suppression.

Brief isoflurane anesthesia regulates striatal AKT-GSK3β signaling and ameliorates motor deficits in a rat model of early-stage Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder primarily affecting the nigrostriatal dopaminergic system. The link between heightened activity of glycogen synthase kinase 3β (GSK3β) and neurodegene‐rative processes has encouraged investigation into the potential disease‐modifying effects of novel GSK3β inhibitors in experimental models of PD. Therefore, the intriguing ability of several anesthetics to readily inhibit GSK3β within the cortex and hippocampus led us to investigate the effects of brief isoflurane anesthesia on striatal GSK3β signaling in naïve rats and in a rat model of early‐stage PD. Deep but brief (20‐min) isoflurane anesthesia exposure increased the phosphorylation of GSK3β at the inhibitory Ser9 residue, and induced phosphorylation of AKTThr308 (protein kinase B; negative regulator of GSK3β) in the striatum of naïve rats and rats with unilateral striatal 6‐hydroxydopamine (6‐OHDA) lesion. The 6‐OHDA protocol produced gradual functional deficiency within the nigrostriatal pathway, reflected as a preference for using the limb ipsilateral to the lesioned striatum at 2 weeks post 6‐OHDA. Interestingly, such motor impairment was not observed in animals exposed to four consecutive isoflurane treatments (20‐min anesthesia every 48 h; treatments started 7 days after 6‐OHDA delivery). However, isoflurane had no effect on striatal or nigral tyrosine hydroxylase (a marker of dopaminergic neurons) protein levels. This brief report provides promising results regarding the therapeutic potential and neurobiological mechanisms of anesthetics in experimental models of PD and guides development of novel disease‐modifying therapies.

ECoG spectrum changes at different xenon-isoflurane anaesthesia depths.

The purpose of this study is to assess the frontal and parietal ECoG spectrum (gamma range) changes during isoflurane and combined xenon-isoflurane anaesthesia in rats. Experiments were carried out on four adult male Sprague-Dawley rats (250-300 g). The anaesthesia was induced with isoflurane and maintained with isoflurane and a xenon-isoflurane mixture. The rats were maintained at two different anaesthetic depths: light (isoflurane anaesthesia) and deep (isoflurane and xenon-isoflurane anaesthesia). The frontal and the parietal cortical activity was assessed by computing the median frequency, spectral edge frequency and functional connectivity between these two areas during light and deep anaesthesia. We noticed a decrease in cortical connectivity under deep isoflurane anaesthesia and an increase in connectivity under deep xenon-isoflurane anaesthesia. Moreover, during xenon-isoflurane anaesthesia, a trend of regularity of electro-cortical activity was present compared with isoflurane anaesthesia. Xenon-isoflurane deep anaesthesia demonstrated a series of specific ECoG features regarding frontoparietal functional connectivity (gamma range connectivity increase) and regularity of the electrocortical activity compared with isoflurane anaesthesia.

Physostigmine and Methylphenidate Induce Distinct Arousal States During Isoflurane General Anesthesia in Rats.

Although emergence from general anesthesia is clinically treated as a passive process driven by the pharmacokinetics of drug clearance, agents that hasten recovery from general anesthesia may be useful for treating delayed emergence, emergence delirium, and postoperative cognitive dysfunction. Activation of central monoaminergic neurotransmission with methylphenidate has been shown to induce reanimation (active emergence) from general anesthesia. Cholinergic neurons in the brainstem and basal forebrain are also known to promote arousal. The objective of this study was to test the hypothesis that physostigmine, a centrally acting cholinesterase inhibitor, induces reanimation from isoflurane anesthesia in adult rats. The dose-dependent effects of physostigmine on time to emergence from a standardized isoflurane general anesthetic were tested. It was then determined whether physostigmine restores righting during continuous isoflurane anesthesia. In a separate group of rats with implanted extradural electrodes, physostigmine was administered during continuous inhalation of 1.0% isoflurane, and the electroencephalogram changes were recorded. Finally, 2.0% isoflurane was used to induce burst suppression, and the effects of physostigmine and methylphenidate on burst suppression probability (BSP) were tested. Physostigmine delayed time to emergence from isoflurane anesthesia at doses ≥0.2 mg/kg (n = 9). During continuous isoflurane anesthesia (0.9% ± 0.1%), physostigmine did not restore righting (n = 9). Blocking the peripheral side effects of physostigmine with the coadministration of glycopyrrolate (a muscarinic antagonist that does not cross the blood-brain barrier) produced similar results (n = 9 each). However, during inhalation of 1.0% isoflurane, physostigmine shifted peak electroencephalogram power from δ (<4 Hz) to θ (4-8 Hz) in 6 of 6 rats. During continuous 2.0% isoflurane anesthesia, physostigmine induced large, statistically significant decreases in BSP in 6 of 6 rats, whereas methylphenidate did not. Unlike methylphenidate, physostigmine does not accelerate time to emergence from isoflurane anesthesia and does not restore righting during continuous isoflurane anesthesia. However, physostigmine consistently decreases BSP during deep isoflurane anesthesia, whereas methylphenidate does not. These findings suggest that activation of cholinergic neurotransmission during isoflurane anesthesia produces arousal states that are distinct from those induced by monoaminergic activation.

Interhemispheric resting-state functional connectivity of the claustrum in the awake and anesthetized states.

The claustrum is a brain region whose function remains unknown, though many investigators suggest it plays a role in conscious attention. Resting-state functional magnetic resonance imaging (RS-fMRI) has revealed how anesthesia alters many functional connections in the brain, but the functional role of the claustrum with respect to the awake versus anesthetized states remains unknown. Therefore, we employed a combination of seed-based RS-fMRI and neuroanatomical tracing to reveal how the anatomical connections of the claustrum are related to its functional connectivity during quiet wakefulness and the isoflurane-induced anesthetic state. In awake rats, RS-fMRI indicates that the claustrum has interhemispheric functional connections with the mediodorsal thalamus (MD) and medial prefrontal cortex (mPFC), as well as other known connections with cortical areas that correspond to the connections revealed by neuroanatomical tracing. During deep isoflurane anesthesia, the functional connections of the claustrum with mPFC and MD were significantly attenuated, while those with the rest of cortex were not significantly altered. These changes in claustral functional connectivity were also observed when seeds were placed in mPFC or MD during RS-fMRI comparisons of the awake and deeply anesthetized states. Collectively, these data indicate that the claustrum has functional connections with mPFC and MD-thalamus that are significantly lessened by anesthesia.

General Anesthetic Conditions Induce Network Synchrony and Disrupt Sensory Processing in the Cortex.

General anesthetics are commonly used in animal models to study how sensory signals are represented in the brain. Here, we used two-photon (2P) calcium activity imaging with cellular resolution to investigate how neuronal activity in layer 2/3 of the mouse barrel cortex is modified under the influence of different concentrations of chemically distinct general anesthetics. Our results show that a high isoflurane dose induces synchrony in local neuronal networks and these cortical activity patterns closely resemble those observed in EEG recordings under deep anesthesia. Moreover, ketamine and urethane also induced similar activity patterns. While investigating the effects of deep isoflurane anesthesia on whisker and auditory evoked responses in the barrel cortex, we found that dedicated spatial regions for sensory signal processing become disrupted. We propose that our isoflurane-2P imaging paradigm can serve as an attractive model system to dissect cellular and molecular mechanisms that induce the anesthetic state, and it might also provide important insight into sleep-like brain states and consciousness.

Oscillatory patterns in hippocampus under light and deep isoflurane anesthesia closely mirror prominent brain states in awake animals.

The hippocampus exhibits a variety of distinct states of activity under different conditions. For instance the rhythmic patterns of activity orchestrated by the theta oscillation during running and REM sleep are markedly different from the large irregular activity (LIA) observed during awake resting and slow wave sleep. We found that under different levels of isoflurane anesthesia activity in the hippocampus of rats displays two distinct states, which have several qualities that mirror the theta and LIA states. These data provide further evidence that the two states are intrinsic modes of the hippocampus; while also characterizing a preparation that could be useful for studying the natural activity states in hippocampus.

Excessive Interleukin 18 Relate the Aggravation of Indomethacin-Induced Intestinal Ulcerogenic Lesions in Adjuvant-Induced Arthritis Rat.

It is well known that rheumatoid arthritis patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) are more susceptible to NSAIDs-induced gastroenteropathy in comparison with other patients. In this study we demonstrate that expression levels of interleukin (IL)-18 are related to aggravation of intestinal ulcerogenic lesions in adjuvant-induced arthritis (AA) rats following oral administration of indomethacin. AA rats were administered oral indomethacin (40 mg/kg) and killed under deep isoflurane anesthesia after 24 h. The small intestinal mucosa was then examined. Oral administration of indomethacin caused hemorrhagic lesions in the small intestinal mucosa of AA rats, and the lesion score of AA rats 24 h after indomethacin treatment was approximately 5.6-fold higher than for normal rats administered indomethacin. IL-18 expression in the small intestinal mucosa of AA rats administered indomethacin was also higher in comparison with normal rats receiving indomethacin. In addition, interferon-γ and nitric oxide levels in the small intestinal mucosa of AA rats were increased following oral administration of indomethacin. It is possible that IL-18 expression in AA rats renders the small intestinal mucosa more sensitive to indomethacin, and that IL-18 may play a role in aggravating intestinal ulcerogenic lesions in AA rats treated with this drug.

Spinal cord transection-induced allodynia in rats--behavioral, physiopathological and pharmacological characterization.

In humans, spinal cord lesions induce not only major motor and neurovegetative deficits but also severe neuropathic pain which is mostly resistant to classical analgesics. Better treatments can be expected from precise characterization of underlying physiopathological mechanisms. This led us to thoroughly investigate (i) mechanical and thermal sensory alterations, (ii) responses to acute treatments with drugs having patent or potential anti-allodynic properties and (iii) the spinal/ganglion expression of transcripts encoding markers of neuronal injury, microglia and astrocyte activation in rats that underwent complete spinal cord transection (SCT). SCT was performed at thoracic T8–T9 level under deep isoflurane anaesthesia, and SCT rats were examined for up to two months post surgery. SCT induced a marked hyper-reflexia at hindpaws and strong mechanical and cold allodynia in a limited (6 cm2) cutaneous territory just rostral to the lesion site. At this level, pressure threshold value to trigger nocifensive reactions to locally applied von Frey filaments was 100-fold lower in SCT- versus sham-operated rats. A marked up-regulation of mRNAs encoding ATF3 (neuronal injury) and glial activation markers (OX-42, GFAP, P2×4, P2×7, TLR4) was observed in spinal cord and/or dorsal root ganglia at T6-T11 levels from day 2 up to day 60 post surgery. Transcripts encoding the proinflammatory cytokines IL-1β, IL-6 and TNF-α were also markedly but differentially up-regulated at T6–T11 levels in SCT rats. Acute treatment with ketamine (50 mg/kg i.p.), morphine (3–10 mg/kg s.c.) and tapentadol (10–20 mg/kg i.p.) significantly increased pressure threshold to trigger nocifensive reaction in the von Frey filaments test, whereas amitriptyline, pregabalin, gabapentin and clonazepam were ineffective. Because all SCT rats developed long lasting, reproducible and stable allodynia, which could be alleviated by drugs effective in humans, thoracic cord transection might be a reliable model for testing innovative therapies aimed at reducing spinal cord lesion-induced central neuropathic pain.

The impact of acepromazine on the efficacy of crystalloid, dextran or ephedrine treatment in hypotensive dogs under isoflurane anesthesia

ObjectiveTo determine the impact of acepromazine on the cardiovascular responses to three treatments for hypotension in dogs during deep isoflurane anesthesia. Study designProspective blinded randomized cross-over experimental design. AnimalsSix adult (2.5 ± 0.5 year old) healthy mixed breed dogs (24.2 ± 7.6 kg). MethodsAnesthesia was induced with propofol (4–6 mg kg−1, IV) and maintained with isoflurane. Each dog received six treatments separated by at least 5 days. Once instrumented, dogs randomly received acepromazine (0.05 mg kg−1) (Ace) or saline (equal volume) (Sal) IV and end-tidal isoflurane (e′Iso) was adjusted to achieve hypotension, defined as a mean blood pressure between 45 and 50 mmHg. Dogs randomly received dextran (D) (7 mL kg−1) or lactated Ringer's (LR) (20 mL kg−1) over 14 minutes, or ephedrine (Eph) (0.1 mg kg−1 followed by 10 μg kg−1 minute−1) throughout the study. Measurements were taken at baseline, 5, 10, 15, 20, 30, and 40 minutes. Data were analyzed with a Latin Square in two factors (Ace/Sal and treatment) for repeated measures, with further comparisons if appropriate (p < 0.05). Resultse′Iso producing hypotension was significantly less following Ace (2.07 ± 0.23%) than Sal (2.43 ± 0.23%). No improvement in cardiac output (CO) was observed with D or LR. LR initially intensified hypotension with a significant reduction in SVR, while D caused a minor improvement in ABP. Eph produced a significant increase in ABP, CO, hemoglobin, oxygen content and delivery. Pre-treatment with Ace minimized ABP improvements with all treatments. Conclusions and clinical relevanceAcepromazine (0.05 mg kg−1 IV) enhanced the hypotensive effect of isoflurane, although it maintained CO. Administration of LR significantly worsens ABP initially by further vasodilation. D caused minimal improvement in ABP. At the infusion studied, Eph effectively countered the cardiovascular depression produced by deep isoflurane anesthesia, but extremes in ABP associated with initial vasoconstriction prevent our recommendation at this dose.

Neurogliaform cells of amygdala: a source of slow phasic inhibition in the basolateral complex

Synaptic inhibition in the amygdala actively participates in processing emotional information. To improve the understanding of interneurons in amygdala networks it is necessary to characterize the GABAergic cell types, their connectivity and physiological roles. We used a mouse line expressing a green fluorescent protein (GFP) under the neuropeptide Y (NPY) promoter. Paired recordings between presynaptic NPY-GFP-expressing (+) cells and postsynaptic principal neurons (PNs) of the basolateral amygdala (BLA) were performed. The NPY-GFP+ neurons displayed small somata and short dendrites embedded in a cloud of highly arborized axon, suggesting a neurogliaform cell (NGFC) type. We discovered that a NPY-GFP+ cell evoked a GABA(A) receptor-mediated slow inhibitory postsynaptic current (IPSC) in a PN and an autaptic IPSC. The slow kinetics of these IPSCs was likely caused by the low concentration and spillover of extracellular GABA. We also report that NGFCs of the BLA fired action potentials phase-locked to hippocampal theta oscillations in anaesthetized rats. When this firing was re-played in NPY+-NGFCs in vitro, it evoked a transient depression of the IPSCs. Presynaptic GABA(B) receptors and functional depletion of synaptic vesicles determined this short-term plasticity. Synaptic contacts made by recorded NGFCs showed close appositions, and rarely identifiable classical synaptic structures. Thus, we report here a novel interneuron type of the amygdala that generates volume transmission of GABA. The peculiar functional mode of NGFCs makes them unique amongst all GABAergic cell types of the amygdala identified so far.

Method of euthanasia affects amygdala plasticity in horizontal brain slices from mice

An important consideration in any terminal experiment is the method used for euthanizing animals. Although the prime consideration is that the method is humane, some methods can have a dramatic impact on experimental outcomes. The standard inhalant anesthetic for experiments in brain slices is isoflurane, which replaced the flammable ethers used in the pioneer days of surgery. To our knowledge, there are no data available evaluating the effects of the method of euthanasia on plasticity changes in brain slices. Here, we compare the magnitude of long-term potentiation (LTP) and long-term depression (LTD) in the lateral nucleus of the amygdala (LA) after euthanasia following either ether or isoflurane anesthesia, as well as in mice decapitated without anesthesia. We found no differences in input–output curves using different methods of euthanasia. The LTP magnitude did not differ between ether and normal isoflurane anesthesia. After deep isoflurane anesthesia LTP induced by high frequency stimulation of cortical or intranuclear afferents was significantly reduced compared to ether anesthesia. In contrast to ether anesthesia and decapitation without anesthesia, the low frequency stimulation of cortical afferents induced a reliable LA-LTD after deep isoflurane anesthesia. Low frequency stimulation of intranuclear afferents only caused LTD after pretreatment with ether anesthesia. The results demonstrate that the method of euthanasia can influence brain plasticity for hours at least in the interface chamber. Therefore, the method of euthanasia is an important consideration when brain plasticity will be evaluated.

A characteristic time sequence of epileptic activity in EEG during dynamic penicillin-induced focal epilepsy—A preliminary study

Penicillin-induced focal epilepsy is a well-known model in experimental epilepsy. However, the dynamic evolution of waveforms, DC-level changes, spectral content and coherence are rarely reported. Stimulated by earlier fMRI findings, we also seek for the early signs preceding spiking activity from frequency domain of EEG signal. In this study, EEG data is taken from previous EEG/fMRI series (six pigs, 20–24 kg) of an experimental focal epilepsy model, which includes dynamic induction of epileptic activity with penicillin (6000IU) injection into the somatosensory cortex during deep isoflurane anaesthesia. No ictal discharges were recorded with this dose. Spike waveforms, DC-level, time–frequency content and coherence of EEG were analysed. Development of penicillin induced focal epileptic activity was not preceded with specific spectral changes. The beginning of interictal spiking was related to power increase in the frequencies below 6 Hz or 20 Hz, and continued to a widespread spectral increase. DC-level and coherence changes were clear in one animal. Morphological evolution of epileptic activity was a collection of the low-amplitude monophasic, bipolar, triple or double spike-wave forms, with an increase in amplitude, up to large monophasic spiking. In conclusion, in the time sequence of induced epileptic activity, immediate shifts in DC-level EEG are plausible, followed by the spike activity-related widespread increase in spectral content. Morphological evolution does not appear to follow a clear continuum; rather, intermingled and variable spike or multispike waveforms generally lead to stabilised activity of high-amplitude monophasic spikes.

Sublinear summation of afferent inputs to the nucleus accumbens in the awake rat

The mechanisms by which the nucleus accumbens integrates afferent input from limbic and cortical structures have been influential in the development of models of psychiatric disorders such as schizophrenia. Previous studies of the response of nucleus accumbens (Nacb) cells to the stimulation of afferent inputs from hippocampus (HC) and prefrontal cortex (PFC) have demonstrated that PFC throughput can be modulated by preceding HC input. Examination of the post-synaptic potential size has suggested, however, that summation of these inputs is sublinear. All studies to date examining Nacb integration of inputs via stimulation of afferents have been performed in the anaesthetized rat. The present experiments compare the response of Nacb cells to different combinations of PFC and HC stimulation in awake and isoflurane-anaesthetized rats that were chronically implanted with both stimulating and recording electrodes. The results of these experiments suggest that summation of afferent input in the Nacb of the awake rat is predominantly sublinear, with only a minority of neurons demonstrating modulation of PFC inputs by the HC in the awake or the anaesthetized animal. The response profile of many cells changed during anaesthesia when compared to the awake condition, and on average showed suppression to PFC input 50 and 150 ms following HC stimulation while under deep isoflurane anaesthesia. These results suggest that sublinear integration of afferent input from the PFC and HC is the dominant mode of integration of Nacb cells in the awake animal, which has implications for corticostriatal models of psychiatric dysfunction.

Xenon and Air Bubble Injection during Cardiopulmonary Bypass

Xenon and Air Bubble Injection during Cardiopulmonary Bypass

Response of hypotensive dogs to dopamine hydrochloride and dobutamine hydrochloride during deep isoflurane anesthesia

To evaluate the dose-related cardiovascular and urine output (UrO) effects of dopamine hydrochloride and dobutamine hydrochloride, administered individually and in combination at various ratios, and identify individual doses that achieve target mean arterial blood pressure (MAP; 70 mm Hg) and cardiac index (CI; 150 mL/kg/min) in dogs during deep isoflurane anesthesia. 10 young clinically normal dogs. Following isoflurane equilibration at a baseline MAP of 50 mm Hg on 3 occasions, dogs randomly received IV administration of dopamine (3, 7, 10, 15, and 20 microg/kg/min), dobutamine (1, 2, 4, 6, and 8 microg/kg/min), and dopamine-dobutamine combinations (3.5:1, 3.5:4, 7:2, 14:1, and 14:4 microg/kg/min) in a crossover study. Selected cardiovascular and UrO effects were determined following 20-minute infusions at each dose. Dopamine caused significant dose-dependent responses and achieved target MAP and CI at 7 microg/kg/min; dobutamine at 2 microg/kg/min significantly affected only CI values. At any dose, dopamine significantly affected UrO, whereas dobutamine did not. Target MAP and CI values were achieved with a dopamine-dobutamine combination at 7:2 microg/kg/min; a dopamine-related dose response for MAP and dopamine- and dobutamine-related dose responses for CI were identified. Changes in UrO were associated with dopamine only. In isoflurane-anesthetized dogs, a guideline dose for dopamine of 7 microg/kg/min is suggested; dobutamine alone did not improve MAP. Data regarding cardiovascular and UrO effects indicated that the combination of dopamine and dobutamine did not provide greater benefit than use of dopamine alone in dogs.

Response of hypotensive dogs to dopamine hydrochloride and dobutamine hydrochloride during deep isoflurane anesthesia

Response of hypotensive dogs to dopamine hydrochloride and dobutamine hydrochloride during deep isoflurane anesthesia

Effects of Altered Consciousness on the Protective Glottic Closure Reflex

The sphincteric function of the larynx, essential to lower airway protection, is most efficiently achieved through strong reflex adduction by both vocal folds. We hypothesize that central facilitation is an essential component of a bilateral brain stem-mediated adductor reflex and that its disturbance by altered consciousness or physiologic sleep could result in weakened sphincteric closure. In 10 adult pigs the glottic closure response was evaluated under light and deep isoflurane anesthesia. The internal branch of the left superior laryngeal nerve was stimulated through bipolar platinum-iridium electrodes, and recording electrodes were positioned in the ipsilateral and contralateral thyroarytenoid muscles. The force of evoked glottic closure was measured with a pressure transducer positioned between the vocal folds. Consistent threshold responses (>90%) were obtained ipsilaterally from 0.5 to 2.0 minimal alveolar concentration (MAC) anesthesia. However, the contralateral reflex responses declined to 6.4% in successive trials as anesthetic levels approached 1.5 to 2.0 MAC. Furthermore, glottic closing force closely reflected these electromyographic changes, declining from 383 mm Hg at 0.5 to 1.0 MAC to 114 mm Hg at 1.5 to 2.0 MAC. Alteration of central facilitation by progressively deeper loss of consciousness abolishes a lower brain stem-mediated crossed adductor reflex, predisposing the subject to a weakened glottic closure response.