Low Concentrations Of Isoflurane Research Articles

An anesthetic protocol for preserving functional network structure in the marmoset monkey brain

Abstract Initiatives towards acquiring large-scale neuroimaging data in non-human primates promise improving translational neuroscience and cross-species comparisons. Crucial among these efforts is the need to expand sample sizes while reducing the impact of anesthesia on the functional properties of brain networks. Yet, the effects of anesthesia on non-human primate brain networks remain unclear. Here, we demonstrate using functional magnetic resonance imaging (fMRI) at 9.4 tesla that isoflurane anesthesia induces a variety of brain states in the marmoset brain with dramatically altered functional connectivity profiles. As an alternative, we recommend using a continuous infusion of the sedative medetomidine, supplemented with a low concentration of isoflurane. Using this protocol in eight marmosets, we observed robust visual activation during flickering light stimulation and identified resting-state networks similar to the awake state. In contrast, isoflurane alone led to a suppressed visual activation and the absence of awake-like network patterns. Comparing states using a graph-theoretical approach, we confirmed that the structure of functional networks is preserved under our proposed anesthesia protocol but is lost using isoflurane alone at concentration levels greater than 1%. We believe that the widespread adoption of this protocol will be a step towards advancing translational neuroscience initiatives in non-human primate neuroimaging. To promote the collaborative use of neuroimaging resources, we openly share our datasets (https://zenodo.org/records/11118775).

Dose-response relationship between the variables of unilateral optogenetic stimulation and transcallosal evoked responses in rat motor cortex.

Efficient interhemispheric integration of neural activity between left and right primary motor cortex (M1) is critical for inter-limb motor control. We employed optogenetic stimulation to establish a framework for probing transcallosal M1–M1 interactions in rats. We performed optogenetic stimulation of excitatory neurons in right M1 of male Sprague-Dawley rats. We recorded the transcallosal evoked potential in contralateral left M1 via chronically implanted electrodes. Recordings were performed under anesthesia combination of dexmedetomidine and a low concentration of isoflurane. We systematically varied the stimulation intensity and duration to characterize the relationship between stimulation parameters in right M1 and the characteristics of the evoked intracortical potentials in left M1. Optogenetic stimulation of right M1 consistently evoked a transcallosal response in left M1 with a consistent negative peak (N1) that sometimes was preceded by a smaller positive peak (P1). Higher stimulation intensity or longer stimulation duration gradually increased N1 amplitude and reduced N1 variability across trials. A combination of stimulation intensities of 5–10 mW with stimulus durations of 1–10 ms were generally sufficient to elicit a robust transcallosal response in most animal, with our optic fiber setup. Optogenetically stimulated excitatory neurons in M1 can reliably evoke a transcallosal response in anesthetized rats. Characterizing the relationship between “stimulation dose” and “response magnitude” (i.e., the gain function) of transcallosal M1-to-M1 excitatory connections can be used to optimize the variables of optogenetic stimulation and ensure stimulation efficacy.

Spatiotemporal patterns of population response in the visual cortex under isoflurane: from wakefulness to loss of consciousness.

Anesthetic drugs are widely used in medicine and research to mediate loss of consciousness (LOC). Isoflurane is a commonly used anesthetic drug; however, its effects on cortical sensory processing, in particular around LOC, are not well understood. Using voltage-sensitive dye imaging, we measured visually evoked neuronal population response from the visual cortex in awake and anesthetized mice at 3 increasing concentrations of isoflurane, thus controlling the level of anesthesia from wakefulness to deep anesthesia. At low concentration of isoflurane, the effects on neuronal measures were minor relative to the awake condition. These effects augmented with increasing isoflurane concentration, while around LOC point, they showed abrupt and nonlinear changes. At the network level, we found that isoflurane decreased the stimulus-evoked intra-areal spatial spread of local neural activation, previously reported to be mediated by horizontal connections, and also reduced intra-areal synchronization of neuronal population. The synchronization between different visual areas decreased with higher isoflurane levels. Isoflurane reduced the population response amplitude and prolonged their latencies while higher visual areas showed increased vulnerability to isoflurane concentration. Our results uncover the changes in neural activity and synchronization at isoflurane concentrations leading to LOC and suggest reverse hierarchical shutdown of cortical areas.

This Month in Anesthesiology

This Month in Anesthesiology

Hypotension Aggravated by Dopamine in a Dog Under Isoflurane Anesthesia

Background: Hypotension (MAP < 60 mmHg) is the most common complication in anesthetic practice and has been identified in 38% of canine patients undergoing general anesthesia for variety of procedures. Normalization of arterial pressure can usually be achieved by decreases in inhalant anesthetic concentrations, fluid administration, and use of inotropes/vasopressors in healthy animals (ASA I) or animals with mild systemic disease (ASA anesthetic risk II). The present report shows an ASA II dog with severe hypotensive crisis [mean arterial pressure (MAP) < 50 mmHg] during general anesthesia, in which the procedure was aborted because hypotension was aggravated by dopamine.Case: A 7-year-old male Bull Terrier was anesthetized for magnetic resonance imaging (MRI) of a tumor in the face. After intramuscular acepromazine (0.01 mg/kg) and meperidine (3 mg/kg), anesthesia was induced with intravenous (IV) ketamine (1 mg/kg) and propofol (2.3 mg/kg) and maintained with isoflurane in oxygen. Ten min after induction of anesthesia MAP was 45 mmHg, while end-tidal isoflurane (ETISO) concentration was 0.5%. End-tidal isoflurane was decreased to 0.3% and an IV bolus of Lactated Ringer’s was initiated (15 mL/kg over 10 min), followed by two ephedrine boluses (0.1mg/kg, IV) administered 5 min apart. MAP remained low (< 50 mmHg) and dopamine constant rate infusion (CRI) was initiated (7.5 μg/kg/min). Ten minutes after dopamine CRI was commenced, MAP was further decreased to 25-22 mmHg. Dopamine CRI was increased to 10 μg/kg/min, but MAP remained < 25 mmHg. Infusion drugs and isoflurane anesthesia were stopped. After the animal was extubated MAP returned 60-70 mmHg.Discussion: Among the drugs used, isoflurane is known for decreasing blood pressure in a dose-related manner because of its vasodilating properties. Hypotension is rarely associated with low end-tidal isoflurane concentrations (0.3-0.5%) in animals that do not present previous evidence of circulatory dysfunction. Acepromazine may have contributed to the hypotensive actions of isoflurane in the case reported here because of its vasodilating effects. Acepromazine has prolonged plasma half-life (7 h) and might also have contributed to the lack efficacy of ephedrine to treat hypotension. Aggravation of hypotension (MAP decreased from 45-50 mmHg to approximately 25 mmHg) by dopamine was unexpected. Aggravation of hypotension during administration of vasopressor doses of dopamine could be related to the activation of the cardiopulmonarychemoreflex (CCR), previously known with the eponym Bezold-Jarisch reflex or due to a prevalence of dopamine´s vasodilatory effects (dopaminergic receptor stimulation) and failure of this drug in promiting increased CO and SVR at the dose ranges used (7.5 to 10 μg/kg/min).. The CCR involves activation of mechano and baroreceptors in the heart, by inotropes such as dopamine and dobutamine. This activation originates vagal afferent impulses to the nucleus tractus solitarii of the spinal cord, which in turn originates parasympathetic afferent impulses to the heart. The consequence is an increase in parasympathetic outflow and decreased sympathetic activity, ultimately producing bradycardia, hypotension, or both.Keywords: acepromazine, Bezold-Jarish reflex, cardiopulmonary chemoreflex, canine, inotropes.

Absence of Neuropathology With Prolonged Isoflurane Sedation in Healthy Adult Rats.

The use of isoflurane sedation for prolonged periods in the critical care environment is increasing. However, isoflurane-mediated neurotoxicity has been widely reported. The goal of the present study was to determine whether long-term exposure to low-dose isoflurane in mechanically ventilated rodents is associated with evidence of neurodegeneration or neuroinflammation. Adult female Sprague-Dawley rats were used in this study. Experimental animals (n=11) were induced with 1.5% isoflurane, intubated, and given a neuromuscular blockade with α-cobratoxin. EEG electrodes were surgically implanted, subcutaneous precordial EKG Ag wire electrodes, and bladder, femoral artery, and femoral vein cannulas permanently placed. After these procedures, the isoflurane concentration was reduced to 0.5% and, in conjunction with the neuromuscular blockade, continued for 7 days. Arterial blood gases and chemistry were measured at 3 time points and core body temperature servoregulated and maintenance IV fluids were given during the 7 days. Experimental animals and untreated controls (n=9) were euthanized on day 7. Immunohistochemical and cytochemical assays did not detect evidence of microgliosis, astrocytosis, neuronal apoptosis or necrosis, amyloidosis, or phosphorylated-tau accumulation. Blood glucose levels were significantly reduced on days 3/4 and 6/7 and partial pressure of oxygen was significantly reduced, but still within the normal range, on day 6/7. All other blood measurements were unchanged. No neuropathologic changes consistent with neurotoxicity were detected in the brain after 1 week of continuous exposure to 0.5% isoflurane in healthy rats. These data suggest that even long exposures to low concentrations of isoflurane have no overt consequences on neuropathology.

Isoflurane Preconditioning Promotes the Survival and Migration of Bone Marrow Stromal Cells

Background: Preconditioning with the volatile anesthetic isoflurane exerts protective effects in animal models of ischemia. The cytoprotective effects of isoflurane are dependent on the expression of hypoxia inducible factor-1 (HIF-1), a dimeric transcription factor that mediates cellular responses to hypoxia. Methods: We investigated the effect of isoflurane preconditioning on bone marrow stromal cell (BMSC) survival and function. Results: Short exposures to low isoflurane concentrations promoted in vitro survival and migration of BMSCs, whereas long exposures and high doses had the opposite effect. At specific doses and times, isoflurane upregulated the expression of HIF-1α and the stromal-derived factor-1 receptor CXCR4, and induced the activation of Akt, similar to hypoxia, and the effect of isoflurane was abrogated by silencing of HIF-1α or inhibition of PI3K/Akt signaling. In vivo experiments showed that isoflurane preconditioning increased the engraftment of BMSCs into the ischemic brain and improved functional recovery in a mouse model of stroke. Conclusion: Isoflurane preconditioning at specific doses and times improves the survival and function of BMSCs through the upregulation of CXCR4 via a mechanism involving HIF-1α expression and the PI3K/Akt pathway, suggesting that anesthetic preconditioning could be developed as a strategy to improve the efficiency of cell therapy.

Isoflurane anesthetic hypersensitivity and progressive respiratory depression in a mouse model with isolated mitochondrial complex I deficiency

Children with mitochondrial disorders are frequently anesthetized for a wide range of operations. These disorders may interfere with the response to surgery and anesthesia. We examined anesthetic sensitivity to and respiratory effects of isoflurane in the Ndufs4 knockout (KO) mouse model. These mice exhibit an isolated mitochondrial complex I (CI) deficiency of the respiratory chain, and they also display clinical signs and symptoms resembling those of patients with mitochondrial CI disease. We investigated seven Ndufs4(-/-) knockout (KO), five Ndufs4(+/-) heterozygous (HZ) and five Ndufs4(+/+) wild type (WT) mice between 22 and 25 days and again between 31 and 34 days post-natal. Animals were placed inside an airtight box, breathing spontaneously while isoflurane was administered in increasing concentrations. Minimum alveolar concentration (MAC) was determined with the bracketing study design, using the response to electrical stimulation to the hind paw. MAC for isoflurane was significantly lower in KO mice than in HZ and WT mice: 0.81% ± 0.01 vs 1.55 ± 0.05% and 1.55 ± 0.13%, respectively, at 22-25 days, and 0.65 ± 0.05%, 1.65 ± 0.08% and 1.68 ± 0.08% at 31-34 days. The KO mice showed severe respiratory depression at lower isoflurane concentrations than the WT and HZ mice. We observed an increased isoflurane anesthetic sensitivity and severe respiratory depression in the KO mice. The respiratory depression during anesthesia was strongly progressive with age. Since the pathophysiological consequences from complex I deficiency are mainly reflected in the central nervous system and our mouse model involves progressive encephalopathy, further investigation of isoflurane effects on brain mitochondrial function is warranted.

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.

Dual Effects of Isoflurane on Neuronal Proliferation/Differentiation

Dual Effects of Isoflurane on Neuronal Proliferation/Differentiation

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.

Effect of Low Concentration Isoflurane with Thiopental Sodium for Craniotomies of Intracranial Space Occupying Lesion

The primary objective of anaesthesia is to facilitate surgery at minimal risk to the patient and to ensure safe optimal recovery following the procedure. The minimal risk to the neurosurgical patient can be achieved with meticulous attention to the detail of intraoperative systemic and brain homeostasis. Safe early recovery from craniotomy necessitates an anaesthetic technique pharmacology adequate to permit early awakening. The present study was designed to observe the effect of different anaesthetic technique that permits early recovery and hemodynamic stability. A total number of thirty patients both male and female age range 18 to 60 yrs having ASA grade-I & II and were randomly selected. They were equally divided into two groups. Group A received TPS infusion and group B received isoflurane inhalation with low dose of TPS infusion. Other drugs remained same for both group. Group A Received induction dose of TPS 4 - 5 mg/kg, maintained by TPS (4 - 5 mg/kg/h infusion), fentanyl (3 mgm/kg bolus, 1 - 2 mgm/ kg/h infusion), oxygen/N2O mixture FiO2 being 0.3. Group B- Received induction dose of TPS 4 - 5 mg/kg and maintained by isoflurane 0.5%, oxygen/ N2O mixture FiO2 being 0.3, fentanyl (3 mgm/kg bolus, 1 - 2 mgm/kg/h infusion), and low dose TPS (1 - 2 mg/kg/h) infusion. In all patients induction was done with TPS 4 - 5 mg/kg and vecuronium (0.1 mg/kg) was used for tracheal intubation, muscle relaxation was maintained by vecuronium 0.01 mg/kg intermittently. Both groups received midazolam (0.1 mg/kg), lignocaine 1.5 mg/kg 2 minutes before induction. Both groups received frusemide 1 mg/ kg just after induction and mannitol 1 gm/kg when scalp incision was given. Anaesthetic procedure was performed with monitoring of hemodynamic variable pulse, blood pressure, SPO2, ETCO2, temperature, urine output. Hemodynamic variable pulse, blood pressure were measure before induction, at intubation, every 15 min. interval and before extubation. Data were analyzed by paired and unpaired student's t-test as appropriate using SPSS software. Hemodynamic response to intubation does not differ significantly between the two groups. But it was observed that at intubation in both groups the pulse and mean arterial blood pressure was raised in compare to baseline, which gradually came down as anaesthetic depth increased and then remained stable all through the procedure. Recovery was evaluated using Aldrete score. Total score significantly differ between two groups up to 30 min after extubation. Group A showed delay recovery up to 30 min in compare to group B. But after 30 min there was no significant difference in scoring between two groups. Total cost of main anaesthetic agent used significantly lower in group A. This study showed that the total infusion of TPS technique was as equally effective as using low concentration of isoflurane with conjunction of low dose TPS regarding perioperative hemodynamic stability. But the cost was minimal in thiopental sodium infusion group with the expense of a little bit delayed recovery. Journal of BSA, Vol. 21, No. 1, January 2008 21-28

Adequate hypnosis at very low isoflurane concentration during craniotomy monitored by electroencephalography

We report a patient with Parkinson's disease undergoing craniotomy for a brain tumor, who had clinically adequate hypnosis at a very low concentration of isoflurane. While the raw EEG showed low-voltage slow electrical activity, the EEG analyzer of the monitor displayed high burst suppression ratios. The role of intracranial pathology and drug therapy as possible causes of the low anesthetic requirement for adequate hypnosis are discussed. This report also draws attention to the possibility of erroneous analysis of burst suppression by EEG modules.

Subunit-specific effects of isoflurane on neuronal Ih in HCN1 knockout mice.

The ionic mechanisms that contribute to general anesthetic actions have not been elucidated, although increasing evidence has pointed to roles for subthreshold ion channels, such as the HCN channels underlying the neuronal hyperpolarization-activated cationic current (Ih). Here, we used conventional HCN1 knockout mice to test directly the contributions of specific HCN subunits to effects of isoflurane, an inhalational anesthetic, on membrane and integrative properties of motor and cortical pyramidal neurons in vitro. Compared with wild-type mice, residual Ih from knockout animals was smaller in amplitude and presented with HCN2-like properties. Inhibition of Ih by isoflurane previously attributed to HCN1 subunit-containing channels (i.e., a hyperpolarizing shift in half-activation voltage [V1/2]) was absent in neurons from HCN1 knockout animals; the remaining inhibition of current amplitude could be attributed to effects on residual HCN2 channels. We also found that isoflurane increased temporal summation of excitatory postsynaptic potentials (EPSPs) in cortical neurons from wild-type mice; this effect was predicted by simulation of anesthetic-induced dendritic Ih inhibition, which also revealed more prominent summation accompanying shifts in V1/2 (an HCN1-like effect) than decreased current amplitude (an HCN2-like effect). Accordingly, anesthetic-induced EPSP summation was not observed in cortical cells from HCN1 knockout mice. In wild-type mice, the enhanced synaptic summation observed with low concentrations of isoflurane contributed to a net increase in cortical neuron excitability. In summary, HCN channel subunits account for distinct anesthetic effects on neuronal membrane properties and synaptic integration; inhibition of HCN1 in cortical neurons may contribute to the synaptically mediated slow-wave cortical synchronization that accompanies anesthetic-induced hypnosis.

Balanced anesthesia and ventilation strategies for an alpaca (Lama pacos) with an increased anesthetic-risk

We report the use of a balanced anesthetic technique in a three-year-old, female Huacaya alpaca with an increased anesthetic risk that underwent an extensive dental surgery. Anesthesia was provided with an infusion of midazolam, fentanyl, S-ketamine and low concentrations of isoflurane in oxygen. The mandibular alveolar nerve was desensitized with a lidocaine-bupivacaine combination. The alpaca showed signs of hypoxemia fifteen minutes after anesthesia induction and arterial blood gases confirmed severe venous admixture. Application of positive end expiratory pressure (PEEP) of 6-9 cm H2O improved the arterial oxygenation. Other cardiopulmonary variables remained within the normal range. At the end of surgery, sarmazenil was administered to antagonize the effects of midazolam and emergence from anesthesia was smooth and uneventful. Flunixine meglumine and a transdermal delivery system for fentanyl were administered for post-operative analgesia. This method of balanced anesthesia allowed for an adequate anesthetic plane and a safe recovery, however, special ventilation strategies (PEEP) had to be applied.

Isoflurane Is a Potent Modulator of Extrasynaptic GABAAReceptors in the Thalamus

Volatile anesthetics are used clinically to produce analgesia, amnesia, unconsciousness, blunted autonomic responsiveness, and immobility. Previous work has shown that the volatile anesthetic isoflurane, at concentrations that produce unconsciousness (250-500 microM), enhances fast synaptic inhibition in the brain mediated by GABA(A) receptors (GABA(A)-Rs). In addition, isoflurane causes sedation at concentrations lower than those required to produce unconsciousness or analgesia. In this study, we found that isoflurane, at low concentrations (25-85 microM) associated with its sedative actions, elicits a sustained current associated with a conductance increase in thalamocortical neurons in the mouse ventrobasal (VB) nucleus. These isoflurane-evoked currents reversed polarity close to the Cl(-) equilibrium potential and were totally blocked by the GABA(A)-R antagonist gabazine. Isoflurane (25-250 microM) produced no sustained current in VB neurons from GABA(A)-R alpha(4)-subunit knockout (Gabra4(-/-)) mice, although 250 microM isoflurane enhanced synaptic inhibition in VB neurons from both wild-type and Gabra4(-/-) mice. These data indicate an obligatory requirement for alpha(4)-subunit expression in the generation of the isoflurane-activated current. In addition, isoflurane directly activated alpha(4)beta(2)delta GABA(A)-Rs expressed in human embryonic kidney 293 cells, and it was more potent at alpha(4)beta(2)delta than at alpha(1)beta(2)gamma(2) receptors (the presumptive extrasynaptic and synaptic GABA(A)-R subtypes in VB neurons). We conclude that the extrasynaptic GABA(A)-Rs of thalamocortical neurons are sensitive to low concentrations of isoflurane. In view of the crucial role of the thalamus in sensory processing, sleep, and cognition, the modulation of these extrasynaptic GABA(A)-Rs by isoflurane may contribute to the sedation and hypnosis associated with low doses of this anesthetic agent.

Effects of perzinfotel on the minimum alveolar concentration of isoflurane in dogs

To determine the effect of IV administration of perzinfotel on the minimum alveolar concentration (MAC) of isoflurane in dogs. Animals-6 healthy sexually intact male Beagles. Dogs were instrumented with a telemetry device that permitted continuous monitoring of heart rate, arterial blood pressure, and body temperature. Dogs were anesthetized with propofol (4 to 6 mg/kg, IV) and isoflurane for 30 minutes before determination of MAC of isoflurane. Isoflurane MAC values were determined 4 times, separated by a minimum of 7 days, before and after IV administration of perzinfotel (0 [control], 5, 10, and 20 mg/kg). Bispectral index and percentage hemoglobin saturation with oxygen (SpO(2)) were monitored throughout anesthesia. Isoflurane MAC was 1.32 +/- 0.14%. Intravenous administration of perzinfotel at 0, 5, 10, and 20 mg/kg decreased isoflurane MAC by 0%, 24%, 30%, and 47%, respectively. Perzinfotel significantly decreased isoflurane MAC values, compared with baseline and control values. The bispectral index typically increased with higher doses of perzinfotel and lower isoflurane concentrations, but not significantly. Heart rate, body temperature, and SpO(2) did not change, but systolic, mean, and diastolic arterial blood pressures significantly increased with decreases in isoflurane MAC after administration of perzinfotel at 10 and 20 mg/kg, compared with 0 and 5 mg/kg. IV administration of perzinfotel decreased isoflurane MAC values. Improved hemodynamics were associated with decreases in isoflurane concentration.

Isoflurane Bidirectionally Modulates the Paired-Pulse Responses in the Rat Hippocampal CA1 Field In Vivo

We studied the effects of isoflurane on hippocampal synaptic transmission and paired-pulse plasticity, under in vivo intact interneuron circuitry. Using rats chronically implanted with electrodes, excitatory postsynaptic potential (EPSP) and population spike amplitude (PSA) were measured in the hippocampal CA1 field by stimulating Schaffer collaterals. The lungs of the rats were mechanically ventilated with 0.25-1.5 minimum alveolar anesthetic concentration (MAC) isoflurane. A control value was obtained in the absence of isoflurane. Isoflurane depressed EPSP responses and enhanced synaptic efficacy. PSA was not depressed except under high concentrations, presumably reflecting a well-balanced combination with the decreased EPSP and enhanced synaptic efficacy. Low concentrations of isoflurane (0.25 and 0.5 MAC) increased paired-pulse facilitation (PPF), whereas a high concentration of isoflurane (1.5 MAC) prolonged the paired-pulse depression. Isoflurane appeared to affect multiple sites of CA1 synapses: 1) the depression of presynaptic glutamatergic transmission as shown by depressed EPSP and increased PPF; 2) the depression of pyramidal neurons as shown by prolonged PPF and depressed PSA under high concentration; and 3) the depression of interneurons as shown by the greater synaptic efficacy. The degree of each of these inhibitory effects seemed to vary at different concentrations, and the overall direction of the synaptic properties may depend on the balances between these inhibitory effects in vivo.

Low Concentration of Isoflurane Promotes the Development of Neurogenic Pulmonary Edema in Spinal Cord Injured Rats

Anesthetics can either promote or inhibit the development of neurogenic pulmonary edema (NPE) after central nervous system (CNS) injury. The influence of isoflurane was examined in male Wistar rats using 1.5%, 2%, 2.5%, 3%, 4%, or 5% isoflurane in air. Epidural balloon compression of the thoracic spinal cord was performed. The development of NPE was examined in vivo and on histologic sections of lung tissue. Animals anesthetized with 1.5% or 3% isoflurane were behaviorally monitored using the BBB and plantar tests for 7 weeks post-injury. The spinal cord was examined using MRI and morphometry of the spared white and gray matter. All animals from the 1.5% and 2% groups developed NPE. Almost 42% of the animals in the 1.5% group died of severe pulmonary hemorrhage and suffocation; x-rays, the pulmonary index, and the histological picture revealed a massive NPE. More than 71% of the animals from the 2.5% and 3% groups did not develop any signs of NPE. Blood pressure after spinal cord compression rose more in the 1.5% group than in the 3% one. In the 1.5% group, the sympathetic ganglionic blockade prevented the neurogenic pulmonary edema development. Animals from the 3% group recovered behaviorally more rapidly than did the animals from the 1.5% group; morphometry and MRI of the lesions showed no differences. Thus, low levels of isoflurane anesthesia promote NPE in rats with a compressed spinal cord and significantly complicates their recovery. The optimal concentration of anesthesia for performing a spinal cord compression lesion is 2.5-3% isoflurane in air.

A new model of severe neurogenic pulmonary edema in spinal cord injured rat

We describe a new model of neurogenic pulmonary edema in spinal cord injured Wistar male rats. The pulmonary edema was elicited by an epidural thoracic balloon compression spinal cord lesion, performed under a low concentration of isoflurane (1.5 or 2%) in air. Anesthesia with 1.5% isoflurane promoted very severe interstitial and intraalveolar neurogenic pulmonary edema with a significantly increased thickness of the alveolar walls and massive pulmonary hemorrhage. In this group, 33% of animals died. Anesthesia with 2% isoflurane promoted severe interstitial and intraalveolar neurogenic pulmonary edema with less thickening of the alveolar walls and pulmonary hemorrhage. For evoking severe neurogenic pulmonary edema in spinal cord injured rats, 2% isoflurane anesthesia would be more suitable. However, if very severe neurogenic pulmonary edema needs to be evoked, spinal cord injury under 1.5% isoflurane anesthesia could be used, but one-third of the animals will be lost.