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Effects of xylazine-ketamine combination on serum ACTH, corticosterone and glucose concentrations in rabbits (Xylazine-ketamine 병용마취가 토끼의 혈중 ACTH, corticosterone 및 glucose 농도에 미치는 영향)

  • Park, Kwon-moo;Li, Long-hua;Han, Seong-kyu;Ryu, Pan-dong
    • Korean Journal of Veterinary Research
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    • v.39 no.1
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    • pp.77-84
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    • 1999
  • Anesthetic agents are useful in inducing the anesthesia for surgical operations and various biological experiments, but they can disturb the body homeostasis and cause the stress in animals. Much efforts have been directed on reducing such side effects of anesthesia. In this work, we measured the serum ACTH, corticosterone and glucose concentration in rabbits to compare the degree of stress induced by two commonly-used anesthetics, ketamine, xylazine, and the combination of xylazine and ketamine. 1. The anesthesia was induced in about 10 min in the rabbits treated with xyalzine, ketamine and xylazine-ketamine. The duration of complete loss of righting reflex were 12, 13 and 115 min in the groups treated with xylazine, ketamine and xylazine-ketamine, respectively. 2. Serum ACTH concentrations in all treatment groups were higher than those in control group. At 30 min after the administration of the drugs, serum ACTH levels in ketamine-treated group were significantly higher than those in control, xylazine- and xylazine-ketamine-treated groups. However, at 1, 2, 5 and 9 hours after the drug administration, serum ACTH levels in xylazine-treated-group were higher than those in control. 3. Serum corticosterone levels in xylazine- and xylazine-ketamine-treated groups were lower than those in control or ketamine-treated groups at 0.5 and 1 hour after the administration. However, at 5 and 9 hours after the administration, serum corticosterone levels in xylazine- and xylazine-ketamine-treated groups were significantly higher than those in ketamine-treated group or control. 4. Serum glucose levels transiently increased to 3 times of the pre-injection levels at 0.5 and 1 hours after the administration in xylazine or xylazine-ketamine-treated groin, but were not changed in control and ketamine-treated group. These results indicate that xylazine-induced stress lasts longer than ketamine-induced, suggesting that the difference in stress-related hormone levels during anesthesia could be due to the differences in modes of actions of individual drugs used and the depth of anesthesia.

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Ketamine-Induced Blood Pressure Lowering in the Rat (흰쥐에서 Ketamine에 의한 혈압하강)

  • Yu Xian-Feng;Kim Shang-Jin;Lee Mun-Young;Kang Hyung-Sub;Kim Jin-Shang
    • Journal of Veterinary Clinics
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    • v.22 no.3
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    • pp.220-227
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    • 2005
  • Although ketamine has been used in the field of anesthetic medicine for its safety and favourable respiratory effects, the cardiovascular effects of ketamine is still controversial. To clarify the action and mechanism of ketamine upon cardiovascular system, arterial blood pressure, tension of aortic ring, left ventricular developed pressure and heart rate were measured in rats, Ketamine produced two types of effects on arterial blood pressure in anesthetized rats; monophasic effect (blood pressure lowering) and biphasic effect (initial transient blood pressure increasing following sustained lowering), The ketamine-induced lowering of aterial blood pressure showed a concentration-dependent manner, inhibited by the pretreament of $MgCl_2$ and potentiated by the pretreatment of $CaCl_2$. The ketamine-induced lowering of aterial blood pressure was suppressed by the pretreatment of nifedipine, verapamil or lidocaine. In phenylephrine-precontracted endothelium intact (+E) aortic rings, ketamine sometimes caused a small enhancement of contraction ($112.5{\pm}3.6{\%}$). However, in many experiments, ketamine produced a concentration-dependent relaxation in +E aortic rings precontracted with either phenylephrine or KCl. Ketamine-induced relaxation was significantly greater in KCl-precontracted strips than phenylephrine-precontracted strips. In phenylephrine-precontracted +E aortic rings, the ketamine-induced vasorelaxation was not suppressed by endothelium removal or by the pretreatment of a nitric oxide synthase inhibitors, L-$N^G$-nitro-arginine and a guanylate cyclase inhibitors, methylene blue, suggesting that the ketamine-induced vasorelaxation is not dependent on the endothelial function. In addition, ketamine elicited an increase in left ventricular developed pressure in perfused hearts accompanied by decrease in heart rate. These results suggest that ketamine could evoke a hypotension due to vasorelaxation and decrease in heart rate in rats. The inhibitory effect of cardiovascular system might be associated with modulation of $Ca^{2+}$ homeostasis.

Chronic administration of ketamine ameliorates the anxiety- and aggressive-like behavior in adolescent mice induced by neonatal maternal separation

  • Shin, Sang Yep;Baek, Nam Jun;Han, Seung Ho;Min, Sun Seek
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.1
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    • pp.81-87
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    • 2019
  • Ketamine has long been used as an anesthetic agent. However, ketamine use is associated with numerous side effects, including flashbacks, amnesia, delirium, and aggressive or violent behavior. Ketamine has also been abused as a cocktail with ecstasy, cocaine, and methamphetamine. Several studies have investigated therapeutic applications of ketamine, demonstrating its antidepressant and anxiolytic effects in both humans and rodents. We recently reported that neonatal maternal separation causes enhanced anxiety- and aggressive-like behaviors in adolescent. In the present study, we evaluated how acute and chronic ketamine administration affected the behavioral consequences of neonatal maternal separation in adolescent mice. Litters were separated from dams for 4 hours per day for 19 days beginning after weaning. Upon reaching adolescence (post-natal day 35-49), mice were acutely (single injection) or chronically (7 daily injections) treated with a sub-anesthetic dose (15 mg/kg) of ketamine. At least 1 h after administration of ketamine, mice were subjected to open-field, elevated-plus maze, and resident-intruder tests. We found that acute ketamine treatment reduced locomotor activity. In contrast, chronic ketamine treatment decreased anxiety, as evidenced by increased time spent on open arms in the elevated-plus maze, and remarkably reduced the number and duration of attacks. In conclusion, the present study suggests that ketamine has potential for the treatment of anxiety and aggressive or violent behaviors.

Antagonism of Xylazine and Ketamine Anesthesia by Yohimbine in Goats (Xylazine과 Ketamine 병용 투여에 대한 Yohimbine의 길항 효과)

  • Nam Tchi-Chou
    • Journal of Veterinary Clinics
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    • v.6 no.1
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    • pp.165-171
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    • 1989
  • Antagonistic effects of yohimbine on xylazine and ketamine anesthesia in goats were studied. Xylazine or ketamine anesthesia alone was not antagonized by yohimbine, but the time for consciousness and recovery in xylazine and ketamine anesthetized goats were remarkably shortened by yohimbine. Reversal effect of yohimbine on the heart rate and body temperature which decreased following xylazine and ketamine was not observed and respiratory rate which increased after xylazine and ketamine was sligtly reduced by yohimbine.

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Effects of Racemic Ketamine on Excitable Membranes of Frog (개구리 세포막에 대한 Racemic Ketamine의 영향)

  • Lee, Jong-Hwa;Frank, George B.
    • The Korean Journal of Pharmacology
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    • v.27 no.2
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    • pp.99-108
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    • 1991
  • The effect of racemic Ketamine HCl was observed on excitable membranes of sciatic nerve fibres and toe muscles from frog. Ketamine significantly depressed the amplitude of the action potential, maximum rate of rise and that of fall of action potentials of sciatic nerve by dose-dependent and time-course manner, and also it produced the inhibition of $K^+-contracture$ in toe muscle. We used two different ways of sucrose gap method to to obtain the better results from sciatic nerve. We observed and compared the effect of ketamine on sciatic nerve with naloxone, 4-AP (4-aminopyridine) and TEA (Tetraethylammonium). Naloxone significantly but not totally blocked the effect of ketamine both on nerve and on skeletal muscle. 4-AP or TEA by itself had a significant depressant effect on the action potentials on nerve by central perfusion (extracellular perfusion), but both of these drugs did not much affect the action of Ketamine on nerve. The reversibility of effect of Ketamine (10 mM) was observed both on nerve and on skeletal muscles when exposed to drug for short duration. The effects of racemic ketamine described may provide to support that one of the mechanisms of the action of Ketamine on nerve and on muscles of frog might be related to non-specifically effect on receptors within the ion channels $(K^+-channel,\;Na^+-channel\;or\;slow\;Ca^{++}\;channel)$ at higher dose which produces anesthetic effect and also it interacts specifically with one of the opioid receptors or subtype of these receptors which is sensitive to Naloxone at lower dose which produces analgesia.

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Facilitation of serotonin-induced contraction of rat mesenteric artery by ketamine

  • Park, Sang Woong;Noh, Hyun Ju;Kim, Jung Min;Kim, Bokyung;Cho, Sung-Il;Kim, Yoon Soo;Woo, Nam Sik;Kim, Sung Hun;Bae, Young Min
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.6
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    • pp.605-611
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    • 2016
  • Ketamine is an anesthetic with hypertensive effects, which make it useful for patients at risk of shock. However, previous ex vivo studies reported vasodilatory actions of ketamine in isolated arteries. In this study, we reexamined the effects of ketamine on arterial tones in the presence and absence of physiological concentrations of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) by measuring the isometric tension of endothelium-denuded rat mesenteric arterial rings. Ketamine little affected the resting tone of control mesenteric arterial rings, but, in the presence of 5-HT (100~200 nM), ketamine ($10{\sim}100{\mu}M$) markedly contracted the arterial rings. Ketamine did not contract arterial rings in the presence of NE (10 nM), indicating that the vasoconstrictive action of ketamine is 5-HT-dependent. The concentration-response curves (CRCs) of 5-HT were clearly shifted to the left in the presence of ketamine ($30{\mu}M$), whereas the CRCs of NE were little affected by ketamine. The left shift of the 5-HT CRCs caused by ketamine was reversed with ketanserin, a competitive 5-$HT_{2A}$ receptor inhibitor, indicating that ketamine facilitated the activation of 5-$HT_{2A}$ receptors. Anpirtoline and BW723C86, selective agonists of 5-$HT_{1B}$ and 5-$HT_{2B}$ receptors, respectively, did not contract arterial rings in the absence or presence of ketamine. These results indicate that ketamine specifically enhances 5-$HT_{2A}$ receptor-mediated vasoconstriction and that it is vasoconstrictive in a clinical setting. The facilitative action of ketamine on 5-$HT_{2A}$ receptors should be considered in ketamine-induced hypertension as well as in the pathogenesis of diseases such as schizophrenia, wherein experimental animal models are frequently generated using ketamine.

The Anesthetic Effects of Xylazine/FentanyNAzaperone and Ketamine Combination in Dogs (개에서 Xylasine/Fentanyl/Azaperone 합제와 Ketamine의 병용마취)

  • 이인헝;연성찬;남치주;권오경
    • Journal of Veterinary Clinics
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    • v.15 no.2
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    • pp.386-393
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    • 1998
  • 임상적으로 널리 쓰이는 xylazine에 fentanyl과 azaperone이 첨가된 합제가 개발 되어 사슴에서 쓰이기 시작하였다. 개에서 이 마취제와 ketamine을 병용하였을 매의 마취효 과를 검토하였다. XFA와 ketamine의 병용마취하였을 매에는 혈청학적으로는 일시적인 과혈 당중을 보인 외의 유의적인 변화는 없었다. XFA 1.1 (Xylazine: 1.1 mg/kg, Fentanyl: 8 ${\mu}g/kg$, Azaperone: 64 ${\mu}g/kg$, )을 투여하였을 매는 ketamine의 농도가 중가함에 따라 진정시간과 회복시간이 길어지지 않았으며,반사반응이 중가하고 근강직이 나타나며 신음소리와 함께 머 리를 흔드는 ketamine의 부작용이 많이 나타났다. 그러나 XFA 2.2 01ylazine: 2.2 mg/kg, Fentanyl: 16 ${\mu}g/kg$, , Azaperone: 128${\mu}g/kg$, 를 투여하였을 때는 농도가 중가함에 따라 마취 시간이 길어지고 부작용도 적게 나타났다. 이상의 결과로 보아,XFA 2.2로 진정시킨 후,병용 투여하는 ketamine의 양으로 마취시간을 조절하는 것이 부작용을 줄이고 안전한 마취를 할 수 있는 유용한 방법이라고 사료된다.

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Antagonistic Effects of Atipamezole and Yohimbine against Anesthesia with Medetomidine and Ketamine Combination in Pigs (돼지에서 Medetomidine-ketamine 마취에 대한 Atipamezole과 Yohimbine의 길항효과)

  • Lee, Jae-Yeon;Kim, Myung-Cheol
    • Journal of Veterinary Clinics
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    • v.28 no.3
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    • pp.291-296
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    • 2011
  • The aims of the present study were to investigate the anesthetic and hemodynamic effects of medetomidine-ketamine combination and to compare antagonistic effects of atipamezole and yohimbine on the recovery of pig from anesthesia induced by medetomidine-ketamine combination. Landrace and Yorkshire cross-bred pigs were evaluated in the present study. Pigs (n = 8) received three different treatments (one treatment per 14 days in a random order). All pigs were injected intramuscularly with medetomidine, and ketamine in a single syringe. Intravenous injections of atipamezole (MKA), yohimbine (MKY), or a control saline solution (MK) were administered 20 minutes after the medetomidine-ketamine combination injection. The intravenous antagonist injections quickly reversed the medetomidine-ketamine induced sedation in the pigs, resulting in a significantly shorter duration of anesthesia in the MKA and MKY groups compared to the MK group. Mean arterial pressure (MAP) levels were significantly lower in the MKA and MKY groups compared to the MK group. Scores for posture and responses to noxious stimuli after atipamezole and yohimbine administration were significantly lower in the MKA and MKY groups than in the MK. In conclusion, the sedative effects and increases in blood pressure induced by a medetomidine-ketamine combination were quickly and smoothly reversed by atipamezole or yohimbine.

Evaluations of vital signs and echocardiographic left ventricular function after the constant rate infusion of lidocaine and/or ketamine in Beagle dogs

  • Kim, Ye-Won;Choi, Miru;Kim, Tae-Jun;Hyun, Changbaig
    • Korean Journal of Veterinary Research
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    • v.55 no.4
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    • pp.215-219
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    • 2015
  • Cardiopulmonary depression of long-term constant rate infusion (CRI) administration of multiple analgesic drugs is important, especially in critically ill dogs. Therefore, this study was conducted to evaluate the effects of lidocaine, ketamine or combined lidocaine-ketamine combination CRI treatment on vital signs and left ventricular (LV) function in healthy dogs. Six adult Beagle dogs were administered either ketamine (initial loading dose of 0.5 mg/kg followed by $10{\mu}g/kg/min$ CRI), lidocaine (initial loading dose of 2 mg/kg followed by 0.025 mg/kg/min CRI), or combined lidocaine-ketamine intravenously. Arterial blood pressure (BP), heart rate (HR), respiratory rate (RR), body temperature (BT) and echocardiographic LV dimensions were measured before administration of medications, immediately after administration of drugs, and then every 10 min for 2 h. There were no significant changes in HR, RR, BT and BP after the administration of either lidocaine CRI, ketamine CRI, or combined lidocaine and ketamine CRI. There were also no significant changes in LV dimensions and stroke volume. The results revealed that treatment with either lidocaine, ketamine or combined lidocaine-ketamine may not cause cardiopulmonary suppression in healthy dogs.

Ketamine-Induced Behavioral Effects Across Different Sub-Anesthetic Dose Ranges in Adolescent and Adult Mice (다양한 마취하 용량에서 케타민에 의해 유발된 청소년기 및 성체 마우스의 행동학적 변화)

  • Choi, Hyung Jun;Im, Soo Jung;Park, Hae Ri;Lee, Seong Mi;Kim, Chul-Eung;Ryu, Seunghyong
    • Korean Journal of Biological Psychiatry
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    • v.27 no.1
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    • pp.27-35
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    • 2020
  • Objectives Ketamine has been reported to have antidepressant effects or psychotomimetic effects. The aim of this study was to investigate the behavioral effects of ketamine treatment at various sub-anesthetic doses in adolescent and adult naïve mice. Methods In each experiment for adolescent and adult mice, a total of 60 male Institute of Cancer Research mice were randomly divided into 6 groups, which were intraperitoneally treated with physiological saline, 10, 20, 30, 40, and 50 mg/kg ketamine for consecutive 3 days. At 1 day after last injection, the locomotor and depressive-like behaviors were evaluated in mice, using open field test (OFT) and forced swim test (FST), respectively. Results In case of adolescent mice, ketamine dose was negatively correlated with total distance traveled in the OFT (Spearman's rho = -0.27, p = 0.039). In case of adult mice, we found significant positive correlation between ketamine dose and duration of immobility in the FST (Spearman's rho = 0.45, p < 0.001). Immobility time in the 50 mg/kg ketamine-treated mice was significantly higher compared to the saline-treated mice (Dunnett's post-hoc test, p = 0.012). Conclusions We found that the repeated treatment with ketamine could decrease the locomotor or prolong the duration of immobility in mice as the dose of ketamine increased. Our findings suggest that sub-anesthetic doses of ketamine might induce schizophrenia-like negative symptoms but not antidepressant effects in naïve laboratory animals.