Effect of Combined Etomidate-Ketamine Anesthesia on Perioperative Electrocardiogram and Postoperative Cognitive Dysfunction of Elderly Patients with Rheumatic Heart Valve Disease Undergoing Heart Valve Replacement

Objective. To explore the effect of combined etomidate-ketamine anesthesia on perioperative electrocardiogram (ECG) and postoperative cognitive dysfunction (POCD) of elderly patients with rheumatic heart valve disease (RHVD) undergoing heart valve replacement. Methods. The data of 100 elderly RHVD patients treated in our hospital from May 2019 to May 2020 were selected for the retrospective analysis, and by adopting the double-blind method, the patients were divided into the ketamine group (n = 50) and the combined group (n = 50) according to the anesthesia methods. During the induction of anesthesia, the patients of the two groups were given a small dose of ketamine (0.5 mg/kg) at 5 μg/kg/min continuously via pump injection until the end of surgery, and on this basis, with the same anesthesia measures, those in the combined group were given etomidate (0.3 mg/kg) additionally. The patients’ perioperative ECG indicators, POCD scores, and Numeric Rating Scale (NRS) scores were compared between the two groups. Results. Compared with the ketamine group, the combined group presented significantly lower incidence of ST-T wave changes after anesthesia induction and at the time of intubation and skin incision ( P < 0.05 ), significantly lower average magnitude of ST-segment depression after anesthesia induction ( P < 0.001 ), significantly lower average magnitude of ST-segment elevation after anesthesia induction and extubation ( P < 0.001 ), significantly lower POCD incidence (6.%, P < 0.05 ), and significantly better NRS score after surgery ( P < 0.001 ). Conclusion. Combined etomidate-ketamine anesthesia can stabilize the perioperative ECG indicators of elderly RHVD patients undergoing heart valve replacement, improve their postoperative cognitive function, and reduce their pain sensation, which should be promoted and applied in practice.

Neuroprotective Effect of Monosialotetrahexosylganglioside (GM1) on Patients with Parkinson’s Disease Anesthetized by Ketamine under Denoising Algorithm-Based Ultrasound Image Diagnosis

This study was to investigate the value of ultrasound technology based on the bilateral filtering noise elimination algorithm in evaluating the neuroprotective effect of monosialoganglioside in ketamine-anesthetized Parkinson’s disease patients. The research subjects were 75 patients with Parkinson’s disease admitted to the hospital. The patients were randomly divided into three groups according to different treatment methods: A (GM1 + ketamine anesthesia group), B (conventional treatment + ketamine anesthesia group), and C (GM1 + nonketamine anesthesia group), with 25 patients in each group. Twenty-five healthy people with similar general data in the three groups (groups A, B, and C) were also selected as the control group (group D). All patients underwent ultrasonography, and ultrasound images were processed using the bilateral filter noise elimination. Structural similarity (SSIM), mean absolute error (MAE), and peak signal to noise ratio (PSNR) were used to evaluate the treatment effect. Plasma phospholipids, the third part of the PD unified score scale, Montreal cognitive assessment scale, and other indicators were analyzed and compared among the four groups. The bilateral filtering image noise was effectively suppressed, and the edge details were kept well. Some of the weak edges and texture information in the image were eliminated, the visual effect was ideal, and the accuracy of the edges of the picture remained good. The serotonin lipid level in group A was greatly lower than the serum phospholipid level in group B after GM1 treatment (6.55 VS 7.84, P < 0.05 ). Compared with that before treatment, the serotonin lipid level of group A patients decreased after the treatment, and the difference was considerable (7.46 VS 6.55, P < 0.05 ). In short, GM1 had a protective effect on the nerves of patients with Parkinson’s disease anesthetized by ketamine.

Ketamine Anesthesia in Electroconvulsive Therapy

Electroconvulsive therapy (ECT) is highly effective both Major Depressive Disorder (MDD) and Bipolar Disorder (BD). Ketamine, an antagonist of the N-Methyl-D-aspartate receptor, has been described to have antidepressant properties. There is a hypothesis that ECT performed with anesthesia using ketamine is more effective than conventional ECT. Also, although ECT is the gold standard for BD and MDD, there are questions about which is more effective, ketamine treatment or ECT, and whether ketamine is more effective when used in combination with ECT. In this chapter, we review the current literature on the effectiveness of ECT and ketamine. Furthermore, we discuss whether ketamine can be an alternative treatment to ECT for patients with TRD.

Ketamine Produces a Long-Lasting Enhancement of CA1 Neuron Excitability

Ketamine is a clinical anesthetic and antidepressant. Although ketamine is a known NMDA receptor antagonist, the mechanisms contributing to antidepression are unclear. This present study examined the loci and duration of ketamine’s actions, and the involvement of NMDA receptors. Local field potentials were recorded from the CA1 region of mouse hippocampal slices. Ketamine was tested at antidepressant and anesthetic concentrations. Effects of NMDA receptor antagonists APV and MK-801, GABA receptor antagonist bicuculline, and a potassium channel blocker TEA were also studied. Ketamine decreased population spike amplitudes during application, but a long-lasting increase in amplitudes was seen during washout. Bicuculline reversed the acute effects of ketamine, but the washout increase was not altered. This long-term increase was statistically significant, sustained for >2 h, and involved postsynaptic mechanisms. A similar effect was produced by MK-801, but was only partially evident with APV, demonstrating the importance of the NMDA receptor ion channel block. TEA also produced a lasting excitability increase, indicating a possible involvement of potassium channel block. This is this first report of a long-lasting increase in excitability following ketamine exposure. These results support a growing literature that increased GABA inhibition contributes to ketamine anesthesia, while increased excitatory transmission contributes to its antidepressant effects.

Excitation of Putative Glutamatergic Neurons in the Rat Parabrachial Nucleus Region Reduces Delta Power during Dexmedetomidine but not Ketamine Anesthesia

Background Parabrachial nucleus excitation reduces cortical delta oscillation (0.5 to 4 Hz) power and recovery time associated with anesthetics that enhance γ-aminobutyric acid type A receptor action. The effects of parabrachial nucleus excitation on anesthetics with other molecular targets, such as dexmedetomidine and ketamine, remain unknown. The hypothesis was that parabrachial nucleus excitation would cause arousal during dexmedetomidine and ketamine anesthesia. Methods Designer Receptors Exclusively Activated by Designer Drugs were used to excite calcium/calmodulin–dependent protein kinase 2α–positive neurons in the parabrachial nucleus region of adult male rats without anesthesia (nine rats), with dexmedetomidine (low dose: 0.3 µg · kg−1 · min−1 for 45 min, eight rats; high dose: 4.5 µg · kg−1 · min−1 for 10 min, seven rats), or with ketamine (low dose: 2 mg · kg−1 · min−1 for 30 min, seven rats; high dose: 4 mg · kg−1 · min−1 for 15 min, eight rats). For control experiments (same rats and treatments), the Designer Receptors Exclusively Activated by Designer Drugs were not excited. The electroencephalogram and anesthesia recovery times were recorded and analyzed. Results Parabrachial nucleus excitation reduced delta power in the prefrontal electroencephalogram with low-dose dexmedetomidine for the 150-min analyzed period, excepting two brief periods (peak median bootstrapped difference [clozapine-N-oxide – saline] during dexmedetomidine infusion = −6.06 [99% CI = −12.36 to −1.48] dB, P = 0.007). However, parabrachial nucleus excitation was less effective at reducing delta power with high-dose dexmedetomidine and low- and high-dose ketamine (peak median bootstrapped differences during high-dose [dexmedetomidine, ketamine] infusions = [−1.93, −0.87] dB, 99% CI = [−4.16 to −0.56, −1.62 to −0.18] dB, P = [0.006, 0.019]; low-dose ketamine had no statistically significant decreases during the infusion). Recovery time differences with parabrachial nucleus excitation were not statistically significant for dexmedetomidine (median difference for [low, high] dose = [1.63, 11.01] min, 95% CI = [−20.06 to 14.14, −20.84 to 23.67] min, P = [0.945, 0.297]) nor low-dose ketamine (median difference = 12.82 [95% CI: −3.20 to 39.58] min, P = 0.109) but were significantly longer for high-dose ketamine (median difference = 11.38 [95% CI: 1.81 to 24.67] min, P = 0.016). Conclusions These results suggest that the effectiveness of parabrachial nucleus excitation to change the neurophysiologic and behavioral effects of anesthesia depends on the anesthetic’s molecular target. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

BIOCHEMICAL PARAMETERS CHANGES OF JAW BONE REMODELING IN EXPERIMENTAL ANIMALS UNDER THE INFLUENCE OF THE SUGGESTED PASTE, INTENDED FOR LOCAL TREATMENT OF CHRONIC GRANULATING PERIODONTITIS OF PERMANENT TEETH IN CHILDREN

The aim of the research was to study in an experiment on rats the biochemical parameters of the jaw bone remodeling under the influence of the developed paste, intended for the local treatment of chronic granulating periodontitis of permanent teeth in children. The experimental research was performed on 36 young rats (males) of the Wistar line (130-150g body weight), which were kept in the vivarium. The animals were divided into 2 groups: an experimental and a control one - 18 rats each. They were operated in sterile conditions under ketamine anesthesia. After applying the alcohol to the skin, a scalpel was used to make an incision along the lower edge of the mandible in the area of the canines and a longitudinal incision of the buccal muscle, then access to the bone was bluntly created. Using a sharp dental probe, a bone defect was modeled, in which the animals of the experimental group were injected with a paste based on comfrey tincture and calcium hydroxide. The control group was operated without the application of paste, the bone defect healed under a blood clot. The surgical wound was sutured in layers with polyamide thread and treated with 1% alcohol solution of diamond green. Blood sampling in experimental animals of both groups (6 rats each) was performed on 7th, 14th and 28th day after surgery. Animals were removed from the experiment by decapitation under ketamine anesthesia. Experimental animals were operated on and removed from the experiment during one day, under the same conditions. Determination of the amount of calcium and inorganic phosphorus in the blood serum of rats was carried out using standard kits of research by "SIMKO Ltd” company, Lviv. The activity of acidic and alkaline phosphatases in the serum was determined using kits of research by BIO-Ld-TEST company, Lachem (Czech Republic) and "Simbj Ltd", Lviv, respectively. In order to determine these parameters in the serum of normal rats, we took blood from 6 healthy young animals that did not participate in the experiment and were on the diet of the vivarium. The research found out that in the healing of artificial bone defects in the lower jaws of rats of the experimental group there were significant fluctuations in calcium and phosphorus levels and changes in the activity of acid phosphatase and alkaline phosphatase in the serum. The amount of Ca and P in the blood of rats decreased sufficiently. Alkaline phosphatase activity increased in both groups on the 7th and 14th day of the experiment, but the difference between the indicators in the groups was 38.35% (p <0.05) and 13.16% (p <0, 01) respectively. This was probably due to the rapid remission of inflammation at the site of surgery in the experimental group, as the paste we developed, which was used to fill a bone defect in this group of animals, has anti-inflammatory properties. Subsequent changes in alkaline phosphatase activity occurred similarly in both groups. This testified to the intensification of bone remodeling processes, as well as bone regeneration and mineralization under the influence of the paste we have developed. Our biochemical researches of the blood of experimental animals confirmed the previously obtained results of morphological and densitometric studies and showed that the recovery of bone wounds of the lower jaws of rats occurs almost equally in the experimental and control groups, and paste based on comfrey tincture and calcium hydroxide promotes bone regeneration at the site of the defect and stimulates osteosynthesis.

Unilateral traumatic brain injury of the left and right hemisphere produces the left hindlimb response in rats

Traumatic brain injury and stroke result in hemiplegia, hemiparesis, and asymmetry in posture. The effects are mostly contralateral; however, ipsilesional deficits may also develop. We here examined whether ablation brain injury and controlled cortical impact (CCI), a rat model of clinical focal traumatic brain injury, both centered over the left or right sensorimotor cortex, induced hindlimb postural asymmetry (HL-PA) with contralesional or ipsilesional limb flexion. The contralesional hindlimb was flexed after left or right side ablation injury. In contrast, both the left and right CCI unexpectedly produced HL-PA with flexion on left side. The flexion persisted after complete spinal cord transection suggesting that CCI triggered neuroplastic processes in lumbar neural circuits enabling asymmetric muscle contraction. Left limb flexion was exhibited under pentobarbital anesthesia. However, under ketamine anesthesia, the body of the left and right CCI rats bent laterally in the coronal plane to the ipsilesional side suggesting that the left and right injury engaged mirror-symmetrical motor pathways. Thus, the effects of the left and right CCI on HL-PA were not mirror-symmetrical in contrast to those of the ablation brain injury, and to the left and right CCI produced body bending. Ipsilateral effects of the left CCI on HL-PA may be mediated by a lateralized motor pathway that is not affected by the left ablation injury. Alternatively, the left-side-specific neurohormonal mechanism that signals from injured brain to spinal cord may be activated by both the left and right CCI but not by ablation injury.

Protective roles of ketamine and xylazine against lightinduced retinal degeneration in rats

Purpose: To study the protective effects of ketamine and xylazine against light exposure-induced retinal degeneration (RD) in rats. Methods: Sprague Dawley rats were divided into three groups viz: light damage before anesthesia (LAE), light damage only (LDO), and control (CON) group which was kept in the dark for 12 - 18 h to habituate before light exposure. LDO group was exposed to light before anesthesia, while LAE group was maintained under anesthesia with ketamine and xylazine. The groups were kept for 120 min in darkness after anesthesia prior to light exposure and they were awakened prior to light damage. Functional assessment was carried out using electroretinography while morphological analysis was carried out using histology and immunochemistry techniques. Results: Ketamine-xylazine combination preserved the function of the retina and protected against light-induced RD based on retinal imaging studies and immunochemistry analysis. Xylazine and ketamine anesthesia provided protection against light-induced retinal damage, and thus reduced photoreceptor cell death. Conclusion: These results indicate that xylazine and ketamine anesthesia offer protection against lightinduced damage and photoreceptor cell death in rats, and therefore, can potentially be developed for use in humans.

Forebrain Acetylcholine Modulates Isoflurane and Ketamine Anesthesia in Adult Mice

Background Cholinergic drugs are known to modulate general anesthesia, but anesthesia responses in acetylcholine-deficient mice have not been studied. It was hypothesized that mice with genetic deficiency of forebrain acetylcholine show increased anesthetic sensitivity to isoflurane and ketamine and decreased gamma-frequency brain activity. Methods Male adult mice with heterozygous knockdown of vesicular acetylcholine transporter in the brain or homozygous knockout of the transporter in the basal forebrain were compared with wild-type mice. Hippocampal and frontal cortical electrographic activity and righting reflex were studied in response to isoflurane and ketamine doses. Results The loss-of-righting-reflex dose for isoflurane was lower in knockout (mean ± SD, 0.76 ± 0.08%, n = 18, P = 0.005) but not knockdown (0.78 ± 0.07%, n = 24, P = 0.021), as compared to wild-type mice (0.83 ± 0.07%, n = 23), using a significance criterion of P = 0.017 for three planned comparisons. Loss-of-righting-reflex dose for ketamine was lower in knockout (144 ± 39 mg/kg, n = 14, P = 0.006) but not knockdown (162 ± 32 mg/kg, n = 20, P = 0.602) as compared to wild-type mice (168 ± 24 mg/kg, n = 21). Hippocampal high-gamma (63 to 100 Hz) power after isoflurane was significantly lower in knockout and knockdown mice compared to wild-type mice (isoflurane-dose and mouse-group interaction effect, F[8,56] = 2.87, P = 0.010; n = 5 to 6 mice per group). Hippocampal high-gamma power after ketamine was significantly lower in both knockout and knockdown mice when compared to wild-type mice (interaction effect F[2,13] = 6.06, P = 0.014). The change in frontal cortical gamma power with isoflurane or ketamine was not statistically different among knockout, knockdown, and wild-type mice. Conclusions These findings suggest that forebrain cholinergic neurons modulate behavioral sensitivity and hippocampal gamma activity during isoflurane and ketamine anesthesia. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New