Optimizing anesthesia and delivery approaches for dosing into lungs of mice
Yurim SeoLonghui QiuMélia MagnenCatharina ConradS. Farshid Moussavi-HaramiMark R. LooneySimon J. Cleary
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Abstract:
Microbes, toxins, therapeutics and cells are often instilled into lungs of mice to model diseases and test experimental interventions. Consistent pulmonary delivery is critical for experimental power and reproducibility, but we observed variation in outcomes between handlers using different anesthetic approaches for intranasal dosing into mice. We therefore used a radiotracer to quantify lung delivery after intranasal dosing under inhalational (isoflurane) versus injectable (ketamine/xylazine) anesthesia in C57BL/6 mice. We found that ketamine/xylazine anesthesia resulted in delivery of a greater proportion (52±9%) of an intranasal dose to lungs relative to isoflurane anesthesia (30±15%). This difference in pulmonary dose delivery altered key outcomes in models of viral and bacterial pneumonia, with mice anesthetized with ketamine/xylazine for intranasal infection with influenza A virus or Pseudomonas aeruginosa developing more robust lung inflammation responses relative to control animals randomized to isoflurane anesthesia. Pulmonary dosing efficiency through oropharyngeal aspiration was not affected by anesthetic method and resulted in delivery of 63±8% of dose to lungs, and a non-surgical intratracheal dosing approach further increased lung delivery to 92±6% of dose. Use of either of these more precise dosing methods yielded greater experimental power in the bacterial pneumonia model relative to intranasal infection. Both anesthetic approach and dosing route can impact pulmonary dosing efficiency. These factors affect experimental power and so should be considered when planning and reporting studies involving delivery of fluids to lungs of mice.The responses of 2 inbred strains of rats to intramuscular doses of ketamine and xylazine, singly and in combination, were studied. A synergistic effect was observed when the 2 drugs were administered together, which resulted in anesthesia with extended analgesia and immobility. Anesthesia was achieved in most rats given 87 mg ketamine/kg of body weight and 13 mg xylazine/kg, beginning 10 to 15 minutes after simultaneous injection and lasting 15 to 30 minutes, then followed by a relatively long period of immobility (mean, 3.8 hours) and reduced responsiveness to external stimuli. Some rats required up to twice this dose for adequate surgical anesthesia. Total doses (initial and supplemental) of up to 3 times the amount were administered with apparent safety.
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Pregnant albino rats were anesthetized with a combination of ketamine and xylazine. A minimal effective dosage of 90 mg/kg for ketamine and 10 mg/kg for xylazine provided satisfactory anesthesia in 92% of the subjects, without adverse effects on gestation or the fetuses.
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Ketamine alone and the combination ketamine-xylazine were evaluated as surgical anesthetics in rabbits. It was found that ketamine alone provided inadequate analgesia for ventral abdominal incisions or exposure of the femur. The combination of xylazine with ketamine did provide adequate enalgesia for both surgical procedures.
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The combination of ketamine HCl and xylazine HCl has been used to immobilize numerous wild and domestic carnivores. The aim of this study was to determined heamotological and biochemical effects of xylazine-ketamine anesthesia on Bozova greyhounds. In this study the anesthetic effects of the ketamine and xylazine were investigated in 8 greyhounds which were in different age, body weight and sex. The animals were injected with the ketamine (10 mg/kg) and xylazine (1 mg/kg) intramuscularly. Heamotological and biochemical findings were recorded before and during anesthesia. The study show that there were no significant differences between before and during anesthesia heamotological and biochemical effects of xylazine-ketamine anesthesia on Bozova greyhounds except increase of glucose, CK and desrease of TP, TRG. In this study; results demonstrated that the combinations of ketamine and xylazine can be used in practice as anesthetics in Bozova greyhounds.
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The Formosan serow (Capricornis swinhoei) is a rare endemic species found in Taiwan. Few studies, including studies on anesthetic protocols, have been conducted on this species. This study evaluates the anesthetic effectiveness of intramuscular xylazine–ketamine and dexmedetomidine–ketamine on captive Formosan serows. Fifty-seven anesthetic events were performed on 22 adults using a combination of xylazine (2.6 ± 0.5 mg/kg) and ketamine (3.7 ± 1.0 mg/kg). Forty-eight anesthetic events were performed on 29 adults using a combination of dexmedetomidine (33.9 ± 4.3 μg/kg) and ketamine (3.4 ± 0.4 mg/kg). Xylazine–ketamine anesthesia was antagonized with tolazoline (3.3 ± 0.8 mg/kg). Dexmedetomidine–ketamine anesthesia was antagonized with atipamezole (272.8 ± 78.2 μg/kg). Both drug combinations showed smooth anesthetic and recovery processes without statistical differences in respiratory rate, heart rate, rectal temperature and hemoglobin oxygen saturation. Dexmedetomidine–ketamine reversed by atipamezole showed a significantly shorter recovery time (1.8 ± 2.3 min) than xylazine–ketamine reversed by tolazoline (4.5 ± 1.7 min) (P < 0.05). Both anesthetic protocols indicated safe and reliable immobilization whereas atipamezole provided better reversal.
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Muscle necrosis in Syrian hamsters resulting from intramuscular injections of ketamine and xylazine.
To assess tissue damage resulting from intramuscular injection of mixtures of ketamine and xylazine, 48 hamsters were given 100, 150 or 200 mg/kg ketamine and 10 mg/kg xylazine in one hind leg and an equal volume of sterile physiologic saline in the other leg. Four hamsters from each group were killed 1, 3, 7 and 14 days after injection and the tissues at the injection sites were examined. There was grossly apparent muscle necrosis in most of the ketamine-xylazine injected legs. By light microscopy, 47 of 48 legs injected with ketamine-xylazine had moderate to extensive muscle necrosis with an acute to chronic inflammatory response, depending on the time elapsed since injection. Microscopic slides of the injection sites were coded, randomized and scored for severity of muscle lesions. Lesion scores for ketamine-xylazine injected legs were significantly higher than controls at all post-injection times. These findings indicate that intramuscular injection of ketamine with xylazine can cause extensive muscle necrosis in hamsters and should not be used for anesthesia in survival procedures.
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Twenty-nine free-ranging Himalayan tahr (Hemitragus jemlahicus) were darted in the Sagarmatha National Park (Nepal) using different combinations of xylazine and ketamine. Animals in Group 1 (n=4) received a mean xylazine–ketamine dose of 2.77±0.99 mg/kg xylazine plus 3.32±0.19 mg/kg ketamine in males and 2.39±0.10 mg/kg xylazine plus 4.29±0.17 mg/kg ketamine in females. Animals in Group 2 (n=25) received a mean xylazine–ketamine dose of 1.70±0.41 mg/kg xylazine plus 3.06±0.74 mg/kg ketamine in males and 1.82±0.29 mg/kg xylazine plus 3.29±0.52 mg/kg ketamine in females. No anesthetic-related mortality was recorded. Anesthesia was reversed by a standard dose of 11 mg/animal of atipamezole administered by intramuscular injection. Although all anesthetic dosages immobilized free-ranging tahr successfully, a quick and smooth recovery was obtained (11.1±5.6 min) only with the dosages of Group 2.
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The anaesthetic effects of xylazine/ketamine drug combination was studied using New-Zealand white (NZW) rabbits. The animals were grouped into three as follows; Group A (Control) animals were pre-medicated with 5mg/kg xylazine (X) intramuscularly (i/m), followed 10 minutes later with 35mg/kg Ketamine(K) i/m .Group B animals were induced with a combination of xylazine/ketamine (XK) followed by a single incremental xylazine at a dose rate of 1.7 mg/kg administered at the time of loss of surgical analgesia. Group C animals were also induced using XK as in control group but incremental XK, 1.75mg/kg and 11.7mg/kg respectively administered as a single injection following onset of pain at the operating site. The result of the study indicate that the onset of anaesthesia marked by loss of righting reflex differ but not significantly (P >0.05) among the three groups. Duration of surgical analgesia lasted significantly (P
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Purpose: This study evaluated the DNA damage caused by repeated doses of xylazine-ketamine and medetomidine-ketamine anesthesia in the liver and kidneys. Methods: In this study, 60 rats were used. The rats were divided into group 1 (xylazine-ketamine), and group 2 (medetomidine-ketamine), and these anesthetic combinations were administered to the rats at repeated doses with 30-min intervals. The effects of these anesthetic agents on the tumor necrosis factor-alpha gene for DNA damage were investigated. Results: According to the gene expression results, it was observed that a single dose of xylazine-ketamine was 2.9-fold expressed, while first and second repeat doses did not show significant changes in expression levels. However, in the case of the third repetition, it was observed to be 3.8-fold overexpressed. In the case of medetomidine-ketamine administration, it was observed that a single-dose application resulted in a 1.04-fold expression, while the first and the third repeat doses showed a significant down expression. The samples from the second repeat dose administration group were found to have insignificant levels of expression. Conclusions: This study can contribute to understanding the safe anesthetic combination in research and operations in which xylazine-ketamine and medetomidine-ketamine combinations are used.
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Ketamine and xylazine were combined to provide anesthesia for coyotes. The drugs were tested in eight adult animals divided equally by sex. A dosage combining 5.5 mg./kg. of each drug provided effective anesthesia for periods from 45 to 60 min.
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