Correction: Ketamine/Xylazine-Induced Corneal Damage in Mice.
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ABSTRACT:
SUBMITTER: PLOS ONE Staff
PROVIDER: S-EPMC4556641 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
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Correction: Ketamine/Xylazine-Induced Corneal Damage in Mice.
PloS one 20150901 9
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Project description:ObjectivesTo explore the effect of ketamine-xylazine anesthesia on light-induced retinal degeneration in rats.MethodsRats were anesthetized with ketamine and xylazine (100 and 5 mg, respectively) for 1 h, followed by a recovery phase of 2 h before exposure to 16,000 lux of environmental illumination for 2 h. Functional assessment by electroretinography (ERG) and morphological assessment by in vivo imaging (optical coherence tomography), histology (hematoxylin/eosin staining, TUNEL assay) and immunohistochemistry (GFAP and rhodopsin staining) were performed at baseline (ERG), 36 h, 7 d and 14 d post-treatment. Non-anesthetized animals treated with light damage served as controls.ResultsKetamine-xylazine pre-treatment preserved retinal function and protected against light-induced retinal degeneration. In vivo retinal imaging demonstrated a significant increase of outer nuclear layer (ONL) thickness in the non-anesthetized group at 36 h (p<0.01) and significant reduction one week (p<0.01) after light damage. In contrast, ketamine-xylazine pre-treated animals showed no significant alteration of total retinal or ONL thickness at either time point (p>0.05), indicating a stabilizing and/or protective effect with regard to phototoxicity. Histology confirmed light-induced photoreceptor cell death and Müller cells gliosis in non-anesthetized rats, especially in the superior hemiretina, while ketamine-xylazine treated rats showed reduced photoreceptor cell death (TUNEL staining: p<0.001 after 7 d), thicker ONL and longer IS/OS. Fourteen days after light damage, a reduction of standard flash induced a-wave amplitudes and a-wave slopes (p = 0.01) and significant alterations in parameters of the scotopic sensitivity function (e.g. Vmax of the Naka Rushton fit p = 0.03) were observed in non-treated vs. ketamine-xylazine treated animals.ConclusionsOur results suggest that pre-treatment with ketamine-xylazine anesthesia protects retinas against light damage, reducing photoreceptor cell death. These data support the notion that anesthesia with ketamine-xylazine provides neuroprotective effects in light-induced cell damage.
| S-EPMC3338443 | biostudies-literature
Project description:Mouse fMRI under anesthesia has become increasingly popular due to improvement in obtaining brain-wide BOLD response. Medetomidine with isoflurane has become well-accepted for resting-state fMRI, but whether this combination allows for stable, expected, and robust brain-wide evoked response in mice has yet to be validated. We thus utilized intravenous infusion of dexmedetomidine with inhaled isoflurane and intravenous infusion of ketamine/xylazine to elucidate whether stable mouse physiology and BOLD response are obtainable in response to simultaneous forepaw and whisker-pad stimulation throughout 8 h. We found both anesthetics result in hypercapnia with depressed heart rate and respiration due to self-breathing, but these values were stable throughout 8 h. Regardless of the mouse condition, brain-wide, robust, and stable BOLD response throughout the somatosensory axis was observed with differences in sensitivity and dynamics. Dexmedetomidine/isoflurane resulted in fast, boxcar-like, BOLD response with consistent hemodynamic shapes throughout the brain. Ketamine/xylazine response showed higher sensitivity, prolonged BOLD response, and evidence for cortical disinhibition as significant bilateral cortical response was observed. In addition, differing hemodynamic shapes were observed between cortical and subcortical areas. Overall, we found both anesthetics are applicable for evoked mouse fMRI studies.
| S-EPMC8222234 | biostudies-literature
Project description:Geriatric animal models are crucial for a better understanding and an improved therapy of age-related diseases. We observed a high mortality of aged mice after anesthesia with a standard dose of ketamine/xylazine, an anesthetic regimen frequently used in laboratory veterinary medicine. C57BL/6-N mice at the age of 2.14?±?0.23?months (young mice) and 26.31?±?2.15?months (aged mice) were anesthetized by intraperitoneal injection of 2?mg ketamine and 0.2?mg xylazine. 4 of 26 aged mice (15.4%) but none of 26 young mice died within 15?min after injection of the anesthetics. The weight of aged mice was significantly higher than that of young mice (32.8?±?5.4?g versus 23.2?±?3.4?g, p?<?0.0001). Thus, aged mice received lower doses of anesthetics in relation to their body weight which are within the lower range of doses recommended in the literature or even beneath. There were no differences between deceased and surviving aged mice concerning their sex, weight and their motor performance prior to anesthesia. Our data clearly show an age-related increase of mortality upon anesthesia with low standard doses of ketamine/xylazine. Assessment of weight and motor performance did not help to predict vulnerability of aged mice to the anesthetics. Caution is necessary when this common anesthetic regimen is applied in aged mice: lower doses or the use of alternative anesthetics should be considered to avoid unexpected mortality. The present data from our geriatric mouse model strongly corroborate an age-adjusted reduction of anesthetic doses to reduce anesthesia-related mortality in aged individuals.
| S-EPMC7081538 | biostudies-literature
Project description:Balanced anesthesia-the use of a combination of drugs to achieve a desired anesthetic plane-offers many benefits, including smoother induction and recovery and fewer adverse effects than occur with individual drugs. Although premedication prior to inhalant anesthesia is routine in other species, mice are commonly induced with gas anesthesia alone. The hypothesis of this study was that premedication with ketamine or xylazine would safely reduce the stress of isoflurane induction and lower the minimum alveolar concentration (MAC) of isoflurane. Young adult male and female C57BL/6J mice were premedicated with ketamine (100 mg/kg), xylazine (4 mg/kg), or isotonic crystalloid (0.1 mL) and were used in 4 experiments. First, isoflurane induction was video recorded under all test conditions, and the videos were scored according to a behavioral ethogram to identify signs of distress. Mice in the ketamine group experienced tremors and ataxia before and dur- ing induction. Therefore, ketamine was given after induction with isoflurane in subsequent experiments. Second, the MAC value for each anesthetic protocol was determined by using quantal and bracketing analysis. Third, mice were anesthetized according to the 3 protocols, and vital parameters were monitored for 60 min. Finally, anesthetized mice were challenged with hypoxia and hypovolemia, and vital parameters were monitored. Premedication with xylazine significantly reduced the stress scores for isoflurane induction (control, 7.3 ± 1.5; ketamine, 6.0 ± 3.0; xylazine, 3.1 ± 1.0). Ketamine and xylazine both reduced the MAC of isoflurane (control, 1.89%; ketamine, 0.96%; xylazine, 1.20%). All mice survived 60 min of anesthesia and the hypoxia-hypovolemia challenge. Premedication with xylazine reduced the stress of induction and lowered the necessary dose of isoflurane in C57BL/6J mice to maintain a surgical plane of anesthesia. We recommend administering xylazine before isoflurane induction and anesthesia of healthy mice that are undergoing procedures in which 100% oxygen is provided and anticipated blood loss is less than 10% to 15% of the total blood volume.
| S-EPMC9536832 | biostudies-literature
Project description:The use of ketamine/xylazine for its anesthetic, anti-inflammatory, and anti-depressant properties could alter other medications and immune functions of the body. Thus, the current study explored how ketamine/xylazine affects the severity of influenza infection in BALB/c and C57Bl/6 mice, monitored for weight loss after intranasal inoculation with A/Puerto Rico/8/34 influenza virus. Mice were inoculated by using a micropipettor to insert 18 μL of control or a suspension of virus into each nostril and allowing the mouse to inhale the material. Several experiments were performed where groups of mice were treated with various combinations of virus and anesthesia and the results compared. Mice were weighed daily and monitored for other signs of illness. The experiments continued until the mice either regained their original weight or died (were euthanized when signs indicated non-recoverable status), which ranged from nine to twenty-three days. Anesthetized mice experienced more weight loss. Additionally, in experiments where the virus suspension was potent enough to lead to death, only mice that were anesthetized died.
| S-EPMC10025899 | biostudies-literature
Project description:Anesthesia for mice is commonly performed through the injection of parenteral agents via the intraperitoneal (IP) route. Variability in anesthetic sensitivities has been noted in mice resulting in inconsistencies in anesthetic depth and/or mortality. Anesthetic protocols that improve consistency and safety are needed. The objectives of this study were to assess the effects of intraperitoneal (IP) ketamine (95 mg/kg) and xylazine (7 mg/kg) alone or combined with lidocaine at 4, 8, or 16 mg/kg on time to loss (LRR) and return (RRR) of righting reflex, duration of immobilization and loss of pedal withdrawal response (PWR), body weight and histopathology in CD-1 mice. In a prospective, randomized trial, 36 male CD-1 mice, 4-6 weeks of age were randomly assigned to 5 groups: saline (SA, n = 4); ketamine-xylazine (KX, n = 8); ketamine-xylazine-lidocaine 4 mg/kg (KXL4, n = 8); ketamine-xylazine-lidocaine 8 mg/kg (KXL8, n = 8); ketamine-xylazine-lidocaine 16 mg/kg (KXL16, n = 8). Two mice in each group were euthanized at day 2 post-injection and the remaining mice were euthanized at day 11 post-injection. After IP injection, LRR and RRR, duration of immobilization and loss of PWR, body weight and histopathology were evaluated. LRR occurred sooner in mice receiving KXL16 compared with KX, with median (range) times of 78 (62-104) and 107 (91-298) seconds, respectively. Loss of PWR occurred in 1, 5, 4, 6 mice for groups KX, KXL4, KXL8, and KXL16 respectively. Median (range) duration of absent PWR was longer in mice receiving KXL16 at 13 (0-30) minutes, compared to KX at 0 (0-9) minutes. Duration of immobilization and RRR were not different between groups. Weight loss occurred 2 days following anesthesia but was not different between groups. Weight gain was significantly greater in all lidocaine groups 11 days post-injection compared to KX. No mortality or histopathologic abnormalities were observed in any group. Lidocaine administered with ketamine and xylazine shortens the onset of anesthesia in mice and improves anesthetic depth without prolonging recovery time.
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Project description:Within the scope of the 3Rs of Russel and Burch, the number of laboratory animals can be reduced by repeated use of an animal. This strategy only becomes relevant, if the total amount of pain, distress or harm the individual animal experiences does not exceed the severity of a single manipulation. For example, when using imaging techniques, an animal can be examined several times during a study, but it has to be anesthetized each time imaging is performed. The severity of anesthesia is thought to be mild according to the Directive 2010/63/EU. However, the Directive does not differentiate between single and repeated anesthesia, although repeated anesthesia may have a greater impact on well-being. Hence, we compared the impact of single and repeated anesthesia (six times at an interval of three to four days) by injection of ketamine and xylazine (KX) on the well-being of adult female and male C57BL/6JRj mice. After anesthesia, well-being of mice was assessed according to a protocol for systematic assessment of well-being including nesting, the Mouse Grimace Scale (MGS), a test for trait anxiety, home cage activity, and the rotarod test for motor activity, food intake, and body weight, as well as corticosterone (metabolite) analysis. Repeated anesthesia increased the MGS in mice of both sexes and caused short-term effects on well-being of female mice in the immediate post-anesthetic period, indicated by longer lasting effects on trait anxiety-related behavior. However, corticosterone metabolite concentrations suggested that mice habituated to the stress induced by repeated KX administration. Hence, the mildly negative effects on well-being of repeated KX anesthesia do not seem to accumulate over time using the respective regimen. However, further observations for severity classification are warranted in order to more specifically determine the duration of mild distress and trait anxiety.
| S-EPMC6145541 | biostudies-literature
Project description:Effective and adequate anesthesia is conducive to better restrain for pigs during surgical or diagnostic procedures This study aimed to evaluate cardiorespiratory and anesthetic effects of ketamine-midazolam-xylazine-sufentanil or tiletamine-zolazepam-xylazine as general anesthetics in miniature pigs. In phase 1, one of the combinations was administered intramuscularly to miniature pigs. The KMXS protocol combined 10 mg kg-1 ketamine, 0.5 mg kg-1 midazolam, and 2 mg kg-1 xylazine with 2 μg kg-1 sufentanil. The TZX protocol combined 2.2 mg kg-1 tiletamine, 2.2 mg kg-1 zolazepam, and 1.4 mg kg-1 xylazine. After treatment, the mean arterial pressure, systolic arterial pressure, diastolic arterial pressure, heart rate, respiratory rate, peripheral hemoglobin oxygen saturation, rectal temperature, and anesthesia quality were recorded. In phase 2, the feasibility of KMXS and TZX as general anesthetics were evaluated for pig castration. In phase 1, both drug combinations provided smooth induction with similar anesthetic effects. The KMXS protocol provided moderate anesthesia for 60-70 minutes in pigs, while the TZX protocol provided 30-45 minutes. In phase 2, castration was completed smoothly in all pigs with little fluctuation in physiological variables. The KMXS protocol is better for medium-term anesthesia, while the TZX protocol is preferable for short-term anesthesia in pigs.
| S-EPMC9275679 | biostudies-literature
Project description:Recent interest in reversal of the hypnotic effects of anesthesia has mainly focused on overcoming a surge in GABA-mediated inhibitory signaling through activation of subcortical arousal circuits or antagonizing GABA receptors. Here we examine the reversal of anesthesia produced from non-GABA agents ketamine/xylazine and the effects of antagonists of adrenoreceptors. These antagonists vary in selectivity and produce temporally unique waking behavior post-anesthesia. We compared two antagonists with differential selectivity for α1- vs. α2-receptors, yohimbine (YOH, 1:40 selectivity) and atipamezole (ATI, 1:8500). Adult mice received intraperitoneal injections of either YOH (4.3 mg/kg), ATI (0.4 mg/kg), or saline after achieving sustained loss of righting following injection of ketamine/xylazine (ketamine: 65.0 mg/kg; xylazine: 9.9 mg/kg). Behaviors indicative of the post-anesthesia, re-animation sequence were carefully monitored and the timing of each behavior relative to anesthesia induction was compared. Both YOH and ATI hastened behaviors indicative of emergence, but ATI was faster than YOH to produce certain behaviors, including whisker movement (YOH: 21.9±1.5 min, ATI: 17.5±0.5 min, p = 0.004) and return of righting reflex (RORR) (YOH: 40.6±8.8 min, ATI: 26.0±1.2 min, p<0.001). Interestingly, although YOH administration hastened early behavioral markers of emergence relative to saline (whisking), the completion of the emergence sequence (time from first marker to appearance of RORR) was delayed with YOH. We attribute this effect to antagonism of α1 receptors by yohimbine. Also notable was the failure of either antagonist to hasten the re-establishment of coordinated motor behavior (e.g., attempts to remove adhesive tape on the forepaw placed during anesthesia) relative to the end of emergence (RORR). In total, our work suggests that in addition to pharmacokinetic effects, re-establishment of normal waking behaviors after anesthesia involves neuronal circuits dependent on time and/or activity.
| S-EPMC6205597 | biostudies-literature
Project description:Alfaxalone is an injectable anesthetic agent that is used in veterinary medicine for general anesthesia. We evaluated the safety and efficacy of alfaxalone delivered through continuous rate infusion by comparing ketamine-xylazine-alfaxalone (KXA) anesthesia with ketamine-xylazine (KX) anesthesia in Sprague-Dawley rats. Anesthesia was induced in male and female rats by using subcutaneous KX. After induction, rats in the KXA group received alfaxalone (10 mg/kg/h IV) for 35 min, whereas rats in the KX group did not receive alfaxalone. At the end of the trial, alfaxalone was discontinued, and xylazine was reversed in all rats by using atipamezole. Throughout anesthesia, we assessed forepaw withdrawal reflex (FPWR), hindpaw withdrawal reflex (HPWR), response to surgical stimulation, heart rate, respiratory rate, SpO?, body temperature, and time to standing. KXA produced a reliable surgical plane of anesthesia, as evidenced by the loss of both FPWR and HPWR and lack of response to surgical stimulation in all 16 rats, whereas only 6 of the 16 rats in the KX group lost HPWR. No rat in the KXA group regained a paw withdrawal reflex during alfaxalone administration, whereas 3 of the 12 rats (25%) in the KX group that reached a surgical plane of anesthesia exited that plane within the 35-min timeframe. Neither heart rate, respiratory rate, SpO?, body temperature, nor time to standing differed between KXA and KX groups; and there were no sex-associated differences in anesthesia response. These results indicate that alfaxalone (10 mg/kg/h IV) delivered through continuous rate infusion, in combination with ketamine and xylazine, provides a safe, prolonged, and reliable surgical plane of anesthesia in rats.
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