Lipid Emulsion And Isoflurane: The Quality Assessment of Anesthesia Parameters In Pigeons

An objective was to evaluate the efficacy of intravenous (IV) emulsified isoflurane formulation for maintenance of general anesthesia and to compare with IV lipid emulsion infusion with inhalation isoflurane in pigeons. The animals was total of 21 healthy, mature pigeons (Columba livia domestica), weighing 318 ± 13 g. Pigeons were anesthetized by emulsified isoflurane (treatment IΙΙ), inhalation isoflurane with IV lipid emulsion (treatment ΙΙ ), and inhalation isoflurane (treatment Ι) alone. Over 50 minutes, wing tone, toe pinch (pedal), and feather pluck reflex were tested every 10 minutes. Data was recorded at 10, 20 and 30 minutes for temperature (T), peripheral hemoglobin oxygen saturation (SpO2) heart rate (HR), and respiratory rate (fR). A scoring system was used to assess parameters related to anesthesia duration and depth. There were no significant differences in hemodynamic variables between the treatment Ι and treatments ΙΙ and IΙΙ, in treatments associated with fat emulsion have shown faster induction, longer anesthesia, more immobilization, and longer recovery time. Furthermore, in anesthesia depth percentages evaluation it was observed that emulsified isoflurane entered the anesthesia deep stage earlier and was removed immediately after discontinuation of administration.Administration of 8% v/v emulsified isoflurane IV was effective in anesthesia rapid induction, stability in depth of anesthesia, rapid withdrawal from anesthesia depth by discontinuation of the infusion, delayed recovery, cardiorespiratory and (T) stability.

Isoflurane in (Super-) Refractory Status Epilepticus: A Multicenter Evaluation

Background We aimed to determine the association between seizure termination and side effects of isoflurane for the treatment of refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) in neurointensive care units (neuro-ICUs). Methods This was a multicenter retrospective study of patients with RSE/SRSE treated with isoflurane for status epilepticus termination admitted to the neuro-ICUs of nine German university centers during 2011–2018. Results We identified 45 patients who received isoflurane for the treatment of RSE/SRSE. During isoflurane treatment, electroencephalograms showed no epileptiform discharges in 33 of 41 (80%) patients, and burst suppression pattern was achieved in 29 of 41 patients (71%). RSE/SRSE was finally terminated after treatment with isoflurane in 23 of 45 patients (51%) for the entire group and in 13 of 45 patients (29%) without additional therapy. Lengths of stay in the hospital and in the neuro-ICU were significantly extended in cases of ongoing status epilepticus under isoflurane treatment (p = 0.01 for length of stay in the hospital, p = 0.049 for length in the neuro-ICU). During isoflurane treatment, side effects were reported in 40 of 45 patients (89%) and mainly included hypotension (n = 40, 89%) and/or infection (n = 20, 44%). Whether side effects occurred did not affect the outcome at discharge. Of 22 patients with follow-up magnetic resonance imaging, 2 patients (9%) showed progressive magnetic resonance imaging alterations that were considered to be potentially associated with RSE/SRSE itself or with isoflurane therapy. Conclusions Isoflurane was associated with a good effect in stopping RSE/SRSE. Nevertheless, establishing remission remained difficult. Side effects were common but without effect on the outcome at discharge.

Isoflurane and Carbon Dioxide Elicit Similar Behavioral Responses in Rats

Euthanasia in rodents is an ongoing topic of debate due to concerns regarding the aversive nature of gases with anesthetic properties such as carbon dioxide (CO2) and isoflurane. The aim of this study was to expand upon previously published work evaluating the aversiveness of CO2 by introducing an isoflurane treatment group in parallel. Aversion was tested using a forced exposure setup and an aversion-avoidance setup. In the first part of the study, 12 naïve female Sprague–Dawley rats were exposed during four consecutive days, once to each of four treatments: isoflurane, fox urine, oxygen, and CO2. In the second part of the study, 24 naïve female Sprague–Dawley rats and 12 rats from the first experiment were exposed to CO2, isoflurane, or both gases. In the forced exposure study, there were no significant differences between CO2 and isoflurane treatments except in line crosses. Overall, rats were more active in the isoflurane and CO2 treatments compared to the control groups, suggesting that isoflurane and CO2 are similarly aversive. In the aversion-avoidance study, rats previously exposed to isoflurane left the dark chamber significantly earlier compared to naïve rats during exposure to isoflurane. We also show that learned aversion to isoflurane is sustained for at least 15 days after initial exposure. Given this result, we suggest that CO2 is superior to isoflurane when euthanizing rodents with prior exposure to isoflurane. Overall, these results confirm previous studies which suggest that care should be taken when considering the serial use of isoflurane as an anesthetic.

Isoflurane-induced miR-140-5p aggravates neurotoxicity in diabetic rats by targeting SNX12

Objectives: MicroRNAs (miRNAs) are widely known as critical regulators in isoflurane-induced neurotoxicity during the development of brain. Isoflurane could aggravate cognitive impairment in diabetic rats. The present study was designed to explore the role and mechanism of miR-140-5p on isoflurane-induced neurotoxicity in diabetic rats. Methods: Diabetic rats model was established by injection of streptozotocin (STZ) and identified by Morris water maze test. Expression of miR-140-5p in diabetic rats under isoflurane treatment was evaluated via qRT-PCR (quantitative real-time polymerase chain reaction). Latency to platform and time spent in the target quadrant were calculated to detect the effect of miR-140-5p on neurotoxicity. The potential target for miR-140-5p was validated via dual luciferase activity assay. Results: Morris water maze test indicated that isoflurane treatment exacerbated STZ-induced cognitive impairment, as demonstrated by increase of latency to platform and decrease of time spent in the target quadrant. MiR-140-5p was up-regulated in diabetic rats under isoflurane treatment. Moreover, knockdown of miR-140-5p attenuated neurotoxicity in diabetic rats. Mechanistically, we found that miR-140-5p could directly bind to SNX12 (sorting nexin 12). The neuroprotective effect of miR-140-5p against isoflurane-aggravated neurotoxicity in diabetic rats dependent on up-regulation of SNX12 and inhibition of cell apoptosis. Conclusions: Knockdown of miR-140-5p relieved isoflurane-aggravated neurotoxicity in diabetic rats through targeting SNX12, suggesting a novel target for neuroprotection in diabetes under isoflurane treatment.

Long-Term Isoflurane Therapy for Refractory Bronchospasm Associated with Herpes Simplex Pneumonia in a Heart Transplant Patient

A 47-year-old man with a history of heart transplant was admitted after severe traumatic brain injury and seizures. During mechanical ventilation, the patient developed bronchospasm that severely compromised respiratory function that led to cardiac arrest. After resuscitation, application of isoflurane through the Anaesthetic Conserving Device (AnaConDa) in the ICU successfully treated bronchospasm, provided adequate sedation, and enabled appropriate ventilation and diagnostic bronchoscopy. A subsequent bronchoalveolar lavage revealed a high amount of Herpes simplex DNA. Herpes simplex pneumonia was diagnosed and treated with acyclovir. Isoflurane treatment was applied for twelve days total without side effects on renal and cerebral function. The patient recovered quickly after the termination of sedation. At discharge, he was fully awake without focal neurological deficiency and his long-term outcome was excellent. This case demonstrates that isoflurane is a treatment option in life-threatening cases of bronchospasm and a safe option for long-term sedation.

Delayed Treatment with Isoflurane Attenuates Lipopolysaccharide and Interferon γ–induced Activation and Injury of Mouse Microglial Cells

Background Isoflurane pretreatment can induce protection against lipopolysaccharide and interferon gamma (IFNgamma)-induced injury and activation of mouse microglial cells. This study's goal was to determine whether delayed isoflurane treatment is protective. Methods Mouse microglial cells were exposed to various concentrations of isoflurane for 1 h immediately after the initiation of lipopolysaccharide (10 or 1000 ng/ml) and IFNgamma (10 U/ml) stimulation or to 2% isoflurane for 1 h at various times after initiation of the stimulation. Nitrite production, lactate dehydrogenase release, and cell viability measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay were assessed after stimulation with lipopolysaccharide and IFNgamma for 24 h. Inducible nitric oxide synthase (iNOS) protein expression was quantified by Western blotting. The iNOS expression in mouse brain was also studied. Results Isoflurane applied 0 and 2 h after the initiation of lipopolysaccharide and IFNgamma stimulation improved cell viability. Isoflurane at 2%, but not at 1 or 3%, reduced the lipopolysaccharide and IFNgamma-induced nitrite production and decreased cell viability. Aminoguanidine, an iNOS inhibitor, also attenuated this decreased cell viability. Chelerythrine and bisindolylmalemide IX, protein kinase C inhibitors, abolished isoflurane effects on cell viability and iNOS expression after lipopolysaccharide and IFNgamma application. Isoflurane also decreased lipopolysaccharide-induced iNOS expression in mouse brain. Late isoflurane application to microglial cells reduced lipopolysaccharide and IFNgamma-induced lactate dehydrogenase release that was not inhibited by aminoguanidine. Conclusions These results suggest that delayed isoflurane treatment can reduce lipopolysaccharide and IFNgamma-induced activation and injury of microglial cells. These effects may be mediated by protein kinase C.

Isoflurane preconditioning uncouples mitochondria and protects against hypoxia-reoxygenation

Ischemic cardiac injury can be substantially alleviated by exposing the heart to pharmacological agents such as volatile anesthetics before occurrence of ischemia-reperfusion. A hallmark of this preconditioning phenomenon is its memory, when cardioprotective effects persist even after removal of preconditioning stimulus. Since numerous studies pinpoint mitochondria as crucial players in protective pathways of preconditioning, the aim of this study was to investigate the effects of preconditioning agent isoflurane on the mitochondrial bioenergetic phenotype. Endogenous flavoprotein fluorescence, an indicator of mitochondrial redox state, was elevated to 195 ± 16% of baseline upon isoflurane application in intact cardiomyocytes, indicating more oxidized state of mitochondria. Isoflurane treatment also elicited partial dissipation of mitochondrial transmembrane potential, which remained depolarized even after anesthetic withdrawal (tetramethylrhodamine fluorescence intensity declined to 83 ± 3 and 81 ± 7% of baseline during isoflurane exposure and washout, respectively). Mild uncoupling, with preserved ATP synthesis, was also detected in mitochondria that were isolated from animals that had been previously preconditioned by isoflurane in vivo, revealing its memory nature. These mitochondria, after exposure to hypoxia and reoxygenation, exhibited better preserved respiration and ATP synthesis compared with mitochondria from nonpreconditioned animals. Partial mitochondrial depolarization was paralleled by a diminished Ca2+ uptake into isoflurane-treated mitochondria, as indicated by the reduced increment in rhod-2 fluorescence when mitochondria were challenged with increased Ca2+ (180 ± 24 vs. 258 ± 14% for the control). In conclusion, isoflurane preconditioning elicits partial mitochondrial uncoupling and reduces mitochondrial Ca2+ uptake. These effects are likely to reduce the extent of the mitochondrial damage after the hypoxic stress.

Delayed cardioprotection with isoflurane: role of reactive oxygen and nitrogen

We determined whether isoflurane can confer delayed cardioprotection in the adult rat by triggering increased production of reactive oxygen (ROS) and nitrogen species (RNS). Our objectives were to determine 1) the concentration of isoflurane that confers delayed cardioprotection in the adult rat, 2) the role of ROS and RNS in the induction of delayed cardioprotection, and 3) the cellular sources of ROS and RNS responsible for induction of delayed cardioprotection by isoflurane. Male Sprague-Dawley rats at 8 wk of age ( n = 8 rats/group) were exposed to 0.5%, 0.8%, 1%, and 2% (vol/vol) isoflurane-100% oxygen for 2 h. Isoflurane conferred delayed cardioprotection 24 h later at a concentration of 0.8% (vol/vol). Administration of manganese (III) tetrakis (4-benzoic acid)porphyrin chloride (MnTBAP), a superoxide scavenger (15 mg/kg ip), or NG-nitro-l-arginine methyl ester (l-NAME), a general nitric oxide synthase inhibitor (15 mg/kg ip), 15 min before isoflurane treatment abolished the delayed cardioprotective effects of isoflurane. MnTBAP and l-NAME had no effect on delayed cardioprotection in untreated hearts. Perfusion of isolated hearts with hydroethidine, a fluorescent probe for superoxide, after isoflurane treatment resulted in a twofold increase in ethidine staining of isoflurane-treated hearts compared with untreated controls, which was attenuated by myxothiazol, an inhibitor of the mitochondrial electron transport chain (0.2 mg/kg ip) and l-NAME (15 mg/kg ip). Nitrite and nitrate content in isoflurane-treated hearts was 1.5-fold higher than in untreated hearts, whereas myocardial reduced glutathione levels were decreased by 13% in 0.8% but not in 1.0% isoflurane-treated hearts. We conclude that isoflurane confers delayed cardioprotection in the adult rat, triggered by ROS and RNS.