Ketamine Anesthesia Research Articles

Synthetic torpor confers cardioprotection against myocardial ischaemia/reperfusion injury in the rat

Abstract Introduction Torpor is a hypothermic, bradycardic, hypometabolic state enabling animals, such as mice, to survive in unfavourable environmental conditions such as cold exposure or reduced food availability. It is thought to be a cardioprotective state. There is interest in developing models that mimic aspects of torpor in clinical settings such as ischaemia-reperfusion injury. The preoptic area of the hypothalamus (POA) has emerged as a key centre for triggering torpor in the mouse. Purpose Induce a synthetic torpor-like state in a species that does not naturally enter torpor (the rat) by chemoactivation of neurons in the POA that correspond to those that induce torpor in the mouse. Test the cardioprotective effects of synthetic torpor in the Langendorff ischaemia-reperfusion preparation. Methods Designer receptors exclusively activated by designer drugs (DREADDs) were used to exogenously activate excitatory neurons in the POA of the rat hypothalamus. Viral vectors (pAAV-CaMKIIa-hM3D(Gq)-mCherry) were stereotaxically injected bilaterally into the POA under ketamine and medetomidine anaesthesia, resulting in expression of DREADDs in excitatory neurons. Control animals received a vector delivering the gene for a fluorescent protein only. DREADD receptors in transfected neurons were activated by subsequent injection of Clozapine-N-Oxide (CNO, 2mg/kg IP), which results in neuronal activation and induces synthetic torpor. Heart rate and core temperature were monitored using implanted telemeters. 2 weeks after vector injection, animals were anaesthetised using 5% isoflurane and culled by cervical dislocation. Hearts were excised and ex-vivo whole heart perfusion at 37°C was performed using the Langendorff apparatus. Hearts were subjected to 30 minutes of global warm ischaemia followed by 60 minutes of reperfusion. Hearts were stained using tetrazolium triphenyl chloride, and infarct size as a proportion of the total heart area calculated. Results Chemoactivation of rat POA neurons induced synthetic torpor characterised by bradycardia (pre: 341.0 ± 17.73bpm, post: 233.4 ± 20.47bpm, paired t (4) = 5.4791, p = .0054) and hypothermia (36.2 ±0.40°C vs 31.6 ± 0.55°C (paired t (4) = 7.9023, p = .0014). CNO had no effect on heart rate or core temperature in control animals. The mean infarct size was significantly lower in synthetic torpor (21.54 ±2.84%) compared to control hearts (29.62 ±2.59%) (unpaired t (23) = 2.1054, p = .0464). Conclusions Synthetic torpor, induced centrally in a species for which torpor is not a natural behaviour, confers striking cardioprotection in an ex-vivo ischaemia-reperfusion model. This novel approach to cardioprotection against myocardial ischaemia/reperfusion injury should be further investigated as a potential therapeutic target for use in clinical practice.

Can we use superglues for superfi cial lacerations?

Objectives: To compare the histopathological and cosmetic outcomes of ethyl-cyanoacrylate to n-butyl-2-cyanoacrylate in rats using an incision wound model. Methods: Two longitudinal incisions were made on the dorsal region of the back of 18 Wistar rats after ketamine anesthesia. Rats were divided into three groups of six: the incisions were closed either using medical tissue adhesive or superglue or were left for secondary wound healing. In each group, three rats were randomly euthanized on the 7th day. The rest were euthanized on the 21st day of the procedure. Tissue samples taken on days 7 and 21 were Histopathologically evaluated blindly by a histologist. The cosmetic appearance was evaluated by a plastic surgeon blinded to the method of closure using a visual analog scale. Results: Histopathological evaluation revealed impaired epithelialization, infl ammation, fi brosis, and dehiscence on connective tissue, and foreign substance reactions were worse in the ethyl-2-cyanoacrylate group when compared with the other groups. A statistically signifi cant diff erence was not found among groups regarding the cosmetic outcome. Conclusions: Cyanoacrylate glues produced for commercial purposes should not be used for the repair of skin lacerations due to their worse histopathological results of epithelialization, infl ammation, fi brosis, dehiscence on connective tissue, and foreign substance reaction. Keywords: Lacerations, Wound closure techniques, Tissue adhesives, Cyanoacrylates, Wound healing.

Opioid-Free Using Ketamine versus Opioid-Sparing Anesthesia during the Intraoperative Period in Video-Assisted Thoracoscopic Surgery: A Randomized Controlled Trial.

Opioids effectively manage perioperative pain but have numerous adverse effects. Opioid-free anesthesia (OFA) eliminates intraoperative opioid use; however, evidence for its use in video-assisted thoracoscopic surgery (VATS) is limited. This study assessed the effect of OFA using ketamine in VATS patients compared to opioid-sparing anesthesia (OSA). A total of 91 patients undergoing VATS lobectomy or segmentectomy were randomized to either the OFA group (ketamine) or the OSA group (remifentanil). The primary outcome was the quality of recovery (QoR) on postoperative day (POD) 1, measured with the QoR-40 questionnaire. Secondary outcomes included postoperative pain scores and adverse events. Both groups had comparable baseline and surgical characteristics. On POD 1, the QoR-40 score was higher in the OFA group than in the OSA group (164.3 ± 10.8 vs. 158.7 ± 10.6; mean difference: 5.6, 95% CI: 1.1, 10.0; p = 0.015), though this did not meet the pre-specified minimal clinically important difference of 6.3. The visual analog scale score was lower in the OFA group as compared to the OSA group at 0-1 h (4.2 ± 2.3 vs. 6.2 ± 2.1; p < 0.001) and 1-4 h after surgery (3.4 ± 1.8 vs. 4.6 ± 1.9; p = 0.003). The OFA group had a lower incidence of PONV (2 [4.4%] vs. 9 [19.6%]; p = 0.049) and postoperative shivering (4 [8.9%] vs. 13 [28.3%]; p = 0.030) than the OSA group at 0-1 h after surgery. Using OFA with ketamine proved feasible, as indicated by the stable intraoperative hemodynamics and absence of intraoperative awareness. Patients undergoing VATS with OFA using ketamine showed a statistically significant, but clinically insignificant, QoR improvement compared to those receiving OSA with remifentanil.

Dexmedetomidine directly binds to and inhibits Toll-like receptor 4

BackgroundWhile a number of anesthetics has been shown potentially associated with neurotoxicity in the developing brain, dexmedetomidine, a drug that was rather recently introduced into the perioperative setting, is considered beneficial from neurological wellbeing. However, the underlying mechanism of how dexmedetomidine affects brain health remains to be determined. Based on our recent study, we hypothesized that dexmedetomidine would directly bind to and inhibit Toll-like receptor 4 (TLR4), a critical receptor largely expressed in microglia and responsible for neurological insult. MethodsWe used TLR4 reporter assays to test if dexmedetomidine attenuates TLR4 activation. Furthermore, a direct binding of dexmedetomidine on TLR4 was tested using photoactivatable medetomidine. Lastly, the effect of dexmedetomidine on ketamine (anesthetic)-induced neurotoxicity was tested in rat pups (P7). ResultsWe showed that dexmedetomidine attenuated TLR4 activation using reporter assay (IC50 = 5.8 µg/mL). Photoactivatable dexmedetomidine delineated its direct binding sites on TLR4. We also showed that dexmedetomidine attenuated microglia activation both in vitro and in vivo. DiscussionWe proposed a novel mechanism of dexmedetomidine-mediated neuroprotection.

MACROSCOPIC ASSESSMENT OF THE DYNAMICS OF THE WOUND PROCESS IN THE TREATMENT OF INFECTED WOUNDS IN RATS USING THE IMMUNOMODULATOR "BLASTOMUNIL"

It is known that wounds and their complications have always bothered humanity because many people have always died from various wounds. Although, nowadays, infected and purulent wounds are found everywhere, and scientific achievements in the treatment of wounds are significant, still the treatment of such wounds is still difficult and far from perfect. At the same time, the search for new ways of treating infected wounds is an urgent issue today.Aim. To carry out a macroscopic assessment of the dynamics of the wound process and to evaluate the effectiveness of the use of the immunomodulator "Blastomunil" in the treatment of infected wounds in rats.Material and methods. The experimental study was conducted in the conditions of the vivarium of the Vinnytsya National Medical University named after M.I. Pirogov. For the experimental work, 65 rats with a body weight of 180-200 g were taken, from which 6 groups of 10 animals each and group No. 7 (5 rats) were formed, which were not involved in the experiment, but blood was taken from them and they practically served as an observation group. All animals of groups I-VI were initially subjected to "ketamine anesthesia" by intramuscular injection of ketamine at the rate of 15 mg/kg of rat body weight. Under anesthesia, wounds of 1.5×1.5 cm were made in the interscapular area. After that, 0.2 ml of a microbial mixture of S. Aureus and P. Аureginosa was injected into the wounds of animals of all groups. The first group of animals was not treated; The II group of animals was treated from the 2nd day by a single intramuscular injection of 0.12 mg of Blastomunil; III group of animals was treated by local application of 0.12 mg Blastomunil to the wound; IV group of animals was treated by local application of 0.02% Decamethoxine (DCM); V group of animals was treated by local application of 0.02% DCM in combination with Blastomunil; animals of group VI at the beginning of the experiment were injected intramuscularly with 0.12 mg, and then a combination of 0.02% DCM and Blastomunil was applied daily locally. From the 1st to the 14th day, the animals were monitored, fed, body T0 measured, the condition of the wound was photographed with subsequent analysis, the animals' behavior was studied, and blood was taken.Results. Starting from the first day, the area of the wounds decreased from the first day to the 14th in all groups, although the rats in the first group felt significantly worse during the first five days than the animals in the other groups. This was manifested by hypodynamia, a decrease in response to sounds and light, as well as a decrease in appetite. At the same time, in animals of other groups, the appetite was good, and the behavior of the rats in the cages was active.Based on visual assessments, the following can be concluded. Contamination of the wound with a microbial mixture in a volume of 0.2 ml, which included S. Aureus and P. Аureginosa (dose 108 CFU/ml) was adequate, since the presence of a purulent-infectious process was achieved, and the reparative processes in animals of group 1 were the worst of all others. At the same time, even a single injection of Blastomunil intramuscularly gave a positive result, because the wound cleared faster and healed better than in the animals of group 1. Local use of Blastomunil accelerated wound healing and reparative processes compared to groups 1 and 2 and not inferior to these indicators in animals where only DCM was used (group 4). In addition, on the 14th day, the wound was completely healed in the animals of the 3rd group, and in the rats of the 4th, the remains of incomplete repair remained. The best macroscopic data were obtained in animals of groups 5 and 6, where wound healing was nearing completion starting from the 10th day. On the 14th day the wounds in the rats of these groups completely healed, epithelized and actively began to be covered with hair.Conclusion. Blastomunil has a positive effect on the wound process, which is manifested by faster wound cleaning, anti-inflammatory effect and reduction of the duration of the reparative process. Moreover, the best results are found when Blastomunil is used simultaneously with DCM.

Phenotype Distinctions in Mice Deficient in the Neuron-Specific α3 Subunit of Na,K-ATPase: Atp1a3tm1Ling/+ and Atp1a3 +/D801Y.

ATP1A3 is a Na,K-ATPase gene expressed specifically in neurons in the brain. Human mutations are dominant and produce an unusually wide spectrum of neurological phenotypes, most notably rapid-onset dystonia parkinsonism (RDP) and alternating hemiplegia of childhood (AHC). Here we compared heterozygotes of two mouse lines, a line with little or no expression (Atp1a3tm1Ling/+) and a knock-in expressing p.Asp801Tyr (D801Y, Atp1a3 +/D801Y). Both mouse lines had normal lifespans, but Atp1a3 +/D801Y had mild perinatal mortality contrasting with D801N mice (Atp1a3 +/D801N), which had high mortality. The phenotypes of Atp1a3tm1Ling/+ and Atp1a3 +/D801Y were different, and testing of each strain was tailored to its symptom range. Atp1a3tm1Ling/+ mice displayed little at baseline, but repeated ethanol intoxication produced hyperkinetic motor abnormalities not seen in littermate controls. Atp1a3 +/D801Y mice displayed robust phenotypes: hyperactivity, diminished posture consistent with hypotonia, and deficiencies in beam walk and wire hang tests. Symptoms also included qualitative motor abnormalities that are not well quantified by conventional tests. Paradoxically, Atp1a3 +/D801Y showed sustained better performance than wild type on the accelerating rotarod. Atp1a3 +/D801Y mice were overactive in forced swimming and afterward had intense shivering, transient dystonic postures, and delayed recovery. Remarkably, Atp1a3 +/D801Y mice were refractory to ketamine anesthesia, which elicited hyperactivity and dyskinesia even at higher dose. Neither mouse line exhibited fixed dystonia (typical of RDP patients), spontaneous paroxysmal weakness (typical of AHC patients), or seizures but had consistent, measurable neurological abnormalities. A gradient of variation supports the importance of studying multiple Atp1a3 mutations in animal models to understand the roles of this gene in human disease.

Critical dynamics in spontaneous EEG predict anesthetic-induced loss of consciousness and perturbational complexity

Consciousness has been proposed to be supported by electrophysiological patterns poised at criticality, a dynamical regime which exhibits adaptive computational properties, maximally complex patterns and divergent sensitivity to perturbation. Here, we investigate dynamical properties of the resting-state electroencephalogram (EEG) of healthy subjects undergoing general anesthesia with propofol, xenon or ketamine. Importantly, all participants were unresponsive under anesthesia, while consciousness was retained only during ketamine anesthesia (in the form of vivid dreams), enabling an experimental dissociation between unresponsiveness and unconsciousness. For each condition, we measure (i) avalanche criticality, (ii) chaoticity, and (iii) criticality-related metrics, revealing that states of unconsciousness are characterized by a distancing from both avalanche criticality and the edge of chaos. We then ask whether these same dynamical properties are predictive of the perturbational complexity index (PCI), a TMS-based measure that has shown remarkably high sensitivity in detecting consciousness independently of behavior. We successfully predict individual subjects’ PCI values with considerably high accuracy from resting-state EEG dynamical properties alone. Our results establish a firm link between perturbational complexity and criticality, and provide further evidence that criticality is a necessary condition for the emergence of consciousness.

Abstract Mo124: New Rho-kinase Inhibitor Reduces Diastolic Dysfunction induced by Estrogen Depletion in Spontaneously Hypertensive Rats

Heart failure with preserved ejection fraction (HFpEF) observed in women with estrogen depletion is a consequence of the reduction of cardioprotection and endothelial dysfunction. Rho-kinase (ROCK) signaling pathway plays a role in cardiac dysfunction consequent to female aging. This work investigated the effects of a new synthetic ROCK inhibitor (iROCK) after oral administration in spontaneously hypertensive rats (SHR) submitted to oophorectomy (OVX). Experimental protocols were approved Animal Care and Use Committee at Universidade Federal do Rio de Janeiro. Under ketamine (80 mg/kg, i.p.) and xylazine (15 mg/kg, i.p.) anesthesia, female SHR submitted to OVX had cardiac function assessed after 8 weeks and compared to SHR-Sham. Eight weeks after OVX, SHR were randomly divided in groups, which were orally treated with either vehicle (DMSO) or iROCK (10 mg/kg) during 2 weeks. Novel iROCK displays potent inhibitory activity for ROCK1 and ROCK2 isoforms, with IC50 of 1.3 μM and 1.7 μM, respectively. At the end of treatment, hemodynamic parameters were evaluated using echocardiography and LV catheterization. Cardiac tissues collected for determining the expression of mitogen-activated protein kinases p38MAPK and extracellular signal-regulated kinase (ERK-1/2) using Western blot technique. After 8 weeks of estrogen depletion, SHR displayed HFpEF because ejection fraction (EF) was 85.2 ± 0.9%, while a reduction in EF from 83.0 ± 2.7 to 64.9 ± 0.9% was only detected after 12 weeks of OVX. Altered filling pressure confirmed the diastolic dysfunction after OVX, because the ratio of rapid mitral flow (E) to rapid wave of mitral annulus tissue Doppler (e') increased from 12.1 ± 1.3 in SHR-Sham to 19.3 ± 0.5. LV end diastolic pressure (LVEDP) increased from 13.4 ± 1.3 to 21.1 ± 4.9 in SHR after 8 weeks post-OVX. Oral administration of iROCK (10 mg/kg) reduced both E/e’ to 16.2 ± 0.5 and LVEDP to 6.4 ± 0.7 mmHg. OVX in SHR increased cardiac p38 MAPK and ERK-1/2 contents by 2.3 and 1.3 fold from SHR-Sham values. In contrast, iROCK reduced p38 overexpression but not altered ERK-1/2 content. Since pro-inflammatory cytokines and oxidative stress activate p38, the recovery of its expression after treatment, indicates that iROCK could reduce the inflammatory component of HF. In conclusion, the new iROCK recovered LV diastolic function induced by estrogen depletion in SHR, through the reduction of myocardial inflammation.

Clinical and Pathological Findings of Ulcerative Prepuce Squamous Cell Carcinoma in a Marwari Horse

Squamous cell carcinoma is one of the muco-cutaneous soft tissue growths occurs in horses. Proliferative external genitalia squamous growth is a common type. This case report is about ulcerative squamous growth which is common in eyeball but uncommon in prepuce area. A Marwari 11 year old stallion was presented to the Veterinary Clinical Complex, Veterinary College and Research Institute, Namakkal with the history of mass in the external genitalia which had increased in size gradually over 12 months with ulceration shown in the last 5 weeks of that period. On clinical examination, ulcerated mass was noticed in the prepuce. Pudental nerve block was done for physical examination. Fine needle aspiration cytology and impression smear didn’t reveal tumour pathology. The presented case was tentatively diagnosed as preputial tumour and planned to perform surgical excision. Under xylazine and ketamine anaesthesia and triple drip maintenance, the preputial tumour mass was excised and samples were sent for histopathology which revealed poorly differentiated squamous cell carcinoma. Post-operative antibiotics, painkillers were administered and wound dressing done for 5 days. Animal had an uneventful recovery without recurrence.

Local activation of CB1 receptors by synthetic and endogenous cannabinoids dampens burst firing mode of reticular thalamic nucleus neurons in rats under ketamine anesthesia.

The reticular thalamic nucleus (RTN) is a thin shell that covers the dorsal thalamus and controls the overall information flow from the thalamus to the cerebral cortex through GABAergic projections that contact thalamo-cortical neurons (TC). RTN neurons receive glutamatergic afferents fibers from neurons of the sixth layer of the cerebral cortex and from TC collaterals. The firing mode of RTN neurons facilitates the generation of sleep-wake cycles; a tonic mode or desynchronized mode occurs during wake and REM sleep and a burst-firing mode or synchronized mode is associated with deep sleep. Despite the presence of cannabinoid receptors CB1 (CB1Rs) and mRNA that encodes these receptors in RTN neurons, there are few works that have analyzed the participation of endocannabinoid-mediated transmission on the electrical activity of RTN. Here, we locally blocked or activated CB1Rs in ketamine anesthetized rats to analyze the spontaneous extracellular spiking activity of RTN neurons. Our results show the presence of a tonic endocannabinoid input, since local infusion of AM 251, an antagonist/inverse agonist, modifies RTN neurons electrical activity; furthermore, local activation of CB1Rs by anandamide or WIN 55212-2 produces heterogeneous effects in the basal spontaneous spiking activity, where the main effect is an increase in the spiking rate accompanied by a decrease in bursting activity in a dose-dependent manner; this effect is inhibited by AM 251. In addition, previous activation of GABA-A receptors suppresses the effects of CB1Rs on reticular neurons. Our results show that local activation of CB1Rs primarily diminishes the burst firing mode of RTn neurons.

The anesthetic management of a child with ohtahara syndrome and severe stridor: a case report

BackgroundOhtahara syndrome is a progressive developmental and epileptic encephalopathy that manifests in the early infantile period. This rare condition is characterized by intractable seizures, psychomotor retardation, and poor prognosis. To date, there are a handful of case reports regarding the anesthetic management of children with Ohtahara syndrome. However, limited reports exist of patients with Ohtahara syndrome who present with difficult airways. This report describes our airway findings and general anesthetic management of a pediatric patient with Ohtahara syndrome undergoing diagnostic bronchoscopy for severe inspiratory stridor.Case presentationA 14-month-old, 9 kg, male patient with Ohtahara syndrome presented with a year-long history of severe inspiratory stridor and was scheduled for bronchoscopy with lavage. On exam, the patient had noisy breathing, was non-verbal with developmental delay, and had poor head control with significant central hypotonia. The patient was induced with ketamine and general anesthesia was maintained with propofol. Bronchoscopic evaluation was completed uneventfully and revealed a diagnosis of laryngotracheomalacia. The patient’s breathing was maintained spontaneously throughout the procedure and no seizures were noted. In the post anesthesia care unit, the patient’s respiratory and cardiovascular function were stable.ConclusionsThis report documents the unusual finding of severe inspiratory stridor in a 14-month-old child diagnosed with Ohtahara syndrome and our anesthetic management during their diagnostic bronchoscopy. Currently, documentation of complex airway pathology present in patients with Ohtahara syndrome is limited and should be further evaluated. This will assist pediatric anesthesiologists as these patients may require careful preoperative assessment, thoughtful airway management, and surgical alternatives on standby.

The Impact of Ketamine-Based Versus Non-Ketamine-Based ECT Anesthesia Regimens on the Severity of Patients’ Depression and Occurrence of Adverse Events: A Systematic Review with Meta-Analysis

Objective: To compare efficacy and safety outcomes for ketamine anesthesia + electroconvulsive therapy (ECT) versus nonketamine anesthesia + ECT in treatment-resistant depression (TRD) patients. Data Sources: PubMed and Embase were searched from the earliest date through November 27, 2023. Study Selection and Data Extraction: Relevant randomized controlled trials (RCTs) of ketamine + ECT versus nonketamine anesthesia + ECT that reported data on remission (odds ratio [OR]), defined as a Hamilton Depression Rating Scale (HAM-D) and Montgomery-Asburg Depression Rating Scale (MADRS) score &lt;8-10) and mean differences (MDs) in HAM-D scores after several ECT sessions were compared using inverse variance methods. The risk of bias (RoB) was assessed using the Cochrane RoB tool. Data Synthesis: Seventeen RCTs (RoB: Low N = 12, Moderate N = 2, High N = 3) with 1181 total patients met inclusion criteria. Patients receiving ECT experienced greater clinical remission (OR: 1.78, [95% confidence interval (CI): 1.08-2.93], I2 = 11%, N = 9) and lower HAM-D scores after the third through sixth ECT sessions as well as the eighth ECT session when ketamine versus nonketamine anesthesia was used. Ketamine use with ECT significantly increased fear with hallucinations (OR: 1.99, [95% CI: 1.11-3.58], I2 = 0%, N = 7) than with nonketamine anesthesia. Relevance to Patient Care and Clinical Practice: Selecting ketamine-based anesthesia could more quickly and profoundly enhance the beneficial effects of ECT for patients with severe TRD, but the balance of benefits to harm is unclear as there may be additional adverse events. Conclusion: Ketamine is a promising anesthesia adjunct to ECT that may enhance antidepressant effects in exchange for more adverse events.

Comparative Brain Microanatomical and Neurochemical Alterations Following the Administration of Seven Oral Artemisinin-Based Combination Therapies in Swiss Mice

Over a decade after artemisinin-based combination therapy (ACT) approval as the most preferred anti-malarial drug. Seven ACTs can be sourced as over-the-counter medications in most African pharmacies without prescription. A comparative neurotoxicity of these ACTs was investigated in an in vivo experimental model. Swiss mice numbering 40, weighing 18 - 26 g were allotted to eight groups (n = 5). Group 1 (normal control [NC]), received distilled water 10 mL, while groups 2 to 8 were administered (5.71 mg artesunate+amodiaquine [AA]); (19.29 mg artesunate+mefloquine [AM]); (10.36 mg artesunate+sulfadoxine+pyrimethamine [ASP]); (19.29 mg artesunate+pyronaridine [APy]); (12.5 mg artemisinin+piperaquine [AP]); (15.42 mg dihydroartemisinin+piperaquine [DP]); and (8 mg artemether+lumefantrine [AL]) per kg body weights, respectively orally for 3 days, but for 2 days in group 6. Animals were sacrificed 24 hrs after last administration under ketamine anaesthesia (100 mg/kg, i.p), and excised brains were evaluated for neurochemical and neurohistological alterations. Oxidative stress markers: malondialdehyde and reduced glutathione significantly (p &lt; 0.05) increased as well as antioxidant enzymes glutathione peroxidase, catalase, superoxide dismutase in ACT-administered groups compared to NC. Neurohistology of hippocampal cornu ammonis 1 (CA1) and cerebellum demonstrated vacuolations, neuronal hypertrophy and atrophy pyramidal, and Purkinje neurons. Immunohistochemistry with glial fibrillary acidic protein antibody demonstrated mild to mostly severe astrogliosis in the ACT-administered groups. In conclusion, oxidative stress markers and antioxidants were elevated in the order DP&gt;APy&gt;AP&gt;ASP&gt;AA&gt;AL&gt;AM. Together with the neurohistology, neurotoxicity were in the order DP&gt;ASP&gt;APy&gt;AP&gt;AL&gt;AA&gt;AM particularly in the hippocampus compared to the cerebellum. KEYWORDS: Artemisinin-based combination therapies, Cerebellum, CA1 region of the hippocampus, Neurodegeneration, Oxidative stress.

Enhancing ketamine anesthesia with midazolam and fentanyl for children's ear surgery: a prospective randomized study.

Myringotomy with tympanostomy tube insertion (MTI) is a superficial surgical procedure used to prevent hearing loss in children with serous otitis media. Intravenous anesthesia, often ketamine, is preferred for this procedure because of its ability to induce sedation without compromising airway reflexes. However, ketamine alone may be insufficient and potentially lead to spontaneous movement during surgery. This study evaluated the effectiveness of midazolam and fentanyl as adjuvants to ketamine in reducing spontaneous movement during MTI and enhancing the quality of recovery. This study involved two groups of 30 patients each: one group received intravenous ketamine (1.5 mg/kg) with an equal volume of normal saline (K group), while the other received a combination of midazolam, fentanyl, and ketamine (0.05 mg/kg, 1 μg/kg, and 1.5 mg/kg, respectively; MFK group). We assessed side effects, intraoperative patient movement, surgeon satisfaction, and emergence agitation scores. The MFK group exhibited significantly lower scores for patient movement (p<0.01) and emergence agitation (p<0.01) and markedly higher surgeon satisfaction scores (p<0.01) than the K group. Administering a midazolam-fentanyl-ketamine combination effectively reduced spontaneous movement during surgery and emergence agitation during recovery without prolonging discharge times in children undergoing MTI.

The impact of scheduling ketamine as an internationally controlled substance on anaesthesia care in Sub-Saharan Africa: a case study and key informant interviews

BackgroundAccess to anaesthesia and surgical care is a major problem for people living in Sub-Saharan Africa. In this region, ketamine is critical for the provision of anaesthesia care. However, efforts to control ketamine internationally as a controlled substance may significantly impact its accessibility. This research therefore aims to estimate the importance of ketamine for anaesthesia and surgical care in Sub-Saharan Africa and assess the potential impact on access to ketamine if it were to be scheduled.MethodsThis research is a mixed-methods study, comprising of a cross-sectional survey at the hospital level in Rwanda, and key informant interviews with experts on anaesthesia care in Sub-Saharan Africa. Data on availability of four anaesthetic agents were collected from hospitals (n = 54) in Rwanda. Semi-structured interviews with 10 key informants were conducted, collecting information on the importance of ketamine, the potential impact of scheduling ketamine internationally, and opinions on misuse of ketamine. Interviews were transcribed verbatim and analysed using a thematic analysis approach.ResultsThe survey conducted in Rwanda found that availability of ketamine and propofol was comparable at around 80%, while thiopental and inhalational agents were available at only about half of the hospitals. Significant barriers impeding access to anaesthesia care were identified, including a general lack of attention given to the specialty by governments, a shortage of anaesthesiologists and migration of trained anaesthesiologists, and a scarcity of medicines and equipment. Ketamine was described as critical for the provision of anaesthesia care as a consequence of these barriers. Misuse of ketamine was not believed to be an issue by the informants.ConclusionKetamine is critical for the provision of anaesthesia care in Sub-Saharan Africa, and its scheduling would have a significantly negative impact on its availability for anaesthesia care.

Myocardial CD34+ Stromal Cells/Telocytes Demonstrate a Dynamic Pattern of Interactions with CD68+ Macrophages During Post-Myocardial Infarction Healing

Introduction: Myocardial CD34-positive (+) stromal cells/telocytes (SC/TCs) have been recently recognized as a novel type of resident cells involved in post-myocardial infarction (MI) repair. Alternatively, CD68-positive (+) macrophages are well-known constituents in this process. However, the relationship between these two cell populations remains mostly obscure. Therefore, this study was aimed to determine whether resident CD34+ SC/TCs and phagocytic CD68+ macrophages have any evident pattern of interactions during the inflammatory and proliferative phases of post-MI scar formation. Methods: A large transmural MI was induced in middle-aged male Sprague-Dawley rats (n = 15) under ketamine and xylazine anesthesia by permanent ligation of the left anterior descending coronary artery. The post-MI rats were infused with BrdU (5-bromo-2'-deoxyuridine) in a dose of 12.5 mg/kg/day for 72 hours via intraperitoneal osmotic minipumps on day 0, 4, or 11 after surgery. The rats were euthanized on day 3, 7 and 14 after MI, and their hearts were processed for histology and immunostaining. Results: On the third day after MI, CD34+ SC/TCs and CD68+ macrophages were absent within the core of the necrotic tissue, whereas both types of cells were juxtaposed in the space surrounding the area of coagulative necrosis. Furthermore, the presence of BrdU labeling in the nuclei of numerous CD34+ SC/TCs suggests their proliferation in the region of the active macrophage clearing. On the seventh day after MI, CD68+ macrophages were observed to have had advanced toward the center of the necrotic region leaving behind the area occupied primarily with acellular basement membranes from the resorbed CMs, whereas most of CD34+ SC/TCs trailed slightly behind. In part, such delay in centripetal progression of CD34+ SC/TCs through the areas of resorption could be attributed to the fact that these cells, in contrast to macrophages, often migrated along the acellular basement membranes left from the dead CMs that required phagocytic removal of necrotic debris to occur first. On the fourteenth day after MI, the population of CD68+ cells appeared notably reduced and demonstrated a patchy distribution predominantly along the remnants of the necrotic tissue. Meanwhile, the substantially expanded population of CD34+ SC/TCs were observed throughout the entire transmural scar, excluding the areas containing dead “mummified” CMs, aggregates of myofibroblasts and the fibroelastic thickening in subepicardial and subendocardial regions. Conclusion: Our findings, for the first time, demonstrate that populations of resident CD34+ SC/TCs and phagocytic CD68+ macrophages exhibit a dynamic pattern of interactions during early phases of post-MI scar formation, suggesting their importance in the process of post-ischemic myocardial healing. Supported by Camden Health Research Initiative. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Features of hemodynamics in elderly patients with coronary heart disease using a combination of propofol, ketamine and fentanyl for induction anesthesia

The aim – to analyze hemodynamic changes in elderly patients with coronary heart disease during coronary artery bypass grafting surgery without cardiopulmonary bypass at the stage of induction into anesthesia using propofol, ketamine and fentanyl.Materials and methods. The results of the examination of 20 patients with coronary artery disease over 60 years of age who underwent coronary artery bypass grafting without the use of artificial circulation are presented. The effect of anesthesia on hemodynamics was assessed by mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), and systemic vascular resistance index (SVRI). The following drugs were used for induction: Propofol 1.5 mg/kg, Ketamine 0.5 mg/kg, Fentanyl 2.0 μg/kg, Pipecuronium bromide 0.1 mg/kg. Anesthesia maintenance: Propofol 4 mg/kg/hour, Fentanyl 2.0 μg/kg/hour.Results and discussion. At the time of admission to the surgery room, hemodynamic parameters reflected that the general condition of patients was stable. After the administration of the combination of drugs for induction propofol + fentanyl + ketamine in the dosage according to the study design, it was found that MAP decreased by 18.71 % (p&lt;0,0001), heart rate decreased by 4.72 % (p = 0,2199), CI decreased by 14.37 % (p = 0,0035), and SVRI decreased by 3.93 % (p = 0,41). After insertion of the intubation tube, it was determined that MAP was 92.34±7.26 % of the baseline values (p = 0,0001), heart rate was 100.81±9.77 % of the baseline data (p = 0,848), CI was determined at 110.38±12.37 % of baseline value (p = 0,0769), and SVRI was 83.57±10.7 % of the baseline, respectively. In 25 minutes after successful tracheal intubation, the parameters were re-registered again: MAP = 86.47±6.07 % of the baseline (p &lt; 0,0001); heart rate = 100.08±5.03 % of the baseline value (p = 0,9711); CI = 108.29±9.95 % of baseline data (p = 0,1248); SVRI = 77.86±9.83 % of the baseline (p = 0,0001).Conclusions. Since hypotension is a frequent side effect of traditional drugs for induction of anesthesia, such as propofol and fentanyl, the addition of ketamine to this combination helps to stabilize hemodynamic parameters and prevents undesirable hemodynamic fluctuations.

Wound healing activity of hydromethanolic Dioscorea bulbifera extract on male wistar rat excision wound models

IntroductionWound healing is a complex physiological process that involves a series of coordinated events that recover structural and functional tissue integrity. The desire to promote nature-based solutions has led to the screening of various plants and herbs for their wound healing potentials with results showing the enhancement of various aspects of the wound healing process. Dioscorea bulbifera possesses a wide range of applications in folk remedies. In traditional Chinese medicine, it is used in the treatment of mumps, goitre, sore throat, gastric cancer and carcinoma of the rectum alone or in combination with other plants. The present study evaluated the effect of hydromethanolic extract of Dioscorea bulbifera (HEDB) on wound size, percentage of wound contraction and tissue hydroxyproline in male Wistar rat excision wound models. MethodsTwenty-five (25) male Wistar rats (180–200 g) were used for the study. They were divided into five (5) groups comprising five (5) animals per group. A circular excision wound (1.5–2 cm) was experimentally induced in each animal following ketamine anaesthesia. Groups I and II served as negative and positive controls and were treated with topical administration of distilled water and petroleum jelly respectively. Groups III, IV and V served as the experimental groups and were treated with 200, 400 and 800 mg/kg of HEDB topically. The diameter of the wound was measured and the wound area and percentage of wound contraction were calculated. Tissue hydroxyproline was determined using tissue excised from the healed portion of the dorsal surface of the animals via coulometric standard procedures. ResultsData from the study indicates that animals in the experimental groups (III, IV and V) had an earlier wound closure compared to the control. Animals treated with 200 mg/kg HEDB (Group III) showed complete wound closure by day 17, whereas animals treated with 400 mg/kg (Group IV) and 800 mg/kg HEDB (Group V) groups achieved complete wound closure by the 18th and 20th day of the experiment respectively. Similarly, all the animals in the experimental groups had significantly increased percentage of wound contraction compared to negative control (P < 0.05). Tissue hydroxyproline was significantly raised amongst the animals treated with 200 and 800 mg/kgHEDB compared to the negative control (p < 0.05). DiscussionEvidence from the study has shown that HEDB possesses potent wound healing activity as the present study has demonstrated that it reduced wound area, and increased wound contraction and tissue hydroxyproline on experimentally induced excision wound male Wistar rat models. These findings provide scientific evidence that validates the traditional medicinal application of Dioscorea bulbifera in promoting wound healing.

Effect of the General Anaesthetic Ketamine on Electrical and Ca2+ Signal Propagation in Arabidopsis thaliana

The systemic electrical signal propagation in plants (i.e., from leaf to leaf) is dependent on GLUTAMATE RECEPTOR-LIKE proteins (GLRs). The GLR receptors are the homologous proteins to the animal ionotropic glutamate receptors (iGluRs) which are ligand-gated non-selective cation channels that mediate neurotransmission in the animal’s nervous system. In this study, we investigated the effect of the general anaesthetic ketamine, a well-known non-competitive channel blocker of human iGluRs, on systemic electrical signal propagation in Arabidopsis thaliana. We monitored the electrical signal propagation, intracellular calcium level [Ca2+]cyt and expression of jasmonate (JA)-responsive genes in response to heat wounding. Although ketamine affected the shape and the parameters of the electrical signals (amplitude and half-time, t1/2) mainly in systemic leaves, it was not able to block a systemic response. Increased [Ca2+]cyt and the expression of jasmonate-responsive genes were detected in local as well as in systemic leaves in response to heat wounding in ketamine-treated plants. This is in contrast with the effect of the volatile general anaesthetic diethyl ether which completely blocked the systemic response. This low potency of ketamine in plants is probably caused by the fact that the critical amino acid residues needed for ketamine binding in human iGluRs are not conserved in plants’ GLRs.

Local orchestration of distributed functional patterns supporting loss and restoration of consciousness in the primate brain

A central challenge of neuroscience is to elucidate how brain function supports consciousness. Here, we combine the specificity of focal deep brain stimulation with fMRI coverage of the entire cortex, in awake and anaesthetised non-human primates. During propofol, sevoflurane, or ketamine anaesthesia, and subsequent restoration of responsiveness by electrical stimulation of the central thalamus, we investigate how loss of consciousness impacts distributed patterns of structure-function organisation across scales. We report that distributed brain activity under anaesthesia is increasingly constrained by brain structure across scales, coinciding with anaesthetic-induced collapse of multiple dimensions of hierarchical cortical organisation. These distributed signatures are observed across different anaesthetics, and they are reversed by electrical stimulation of the central thalamus, coinciding with recovery of behavioural markers of arousal. No such effects were observed upon stimulating the ventral lateral thalamus, demonstrating specificity. Overall, we identify consistent distributed signatures of consciousness that are orchestrated by specific thalamic nuclei.