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在特发性癫痫犬和健康对照犬中给予氯胺酮:我们能否通过光谱检测脑代谢物反应的差异?

Ketamine administration in idiopathic epileptic and healthy control dogs: Can we detect differences in brain metabolite response with spectroscopy?

作者信息

Wieser Manuela, Beckmann Katrin Melanie, Kutter Annette P N, Mauri Nico, Richter Henning, Zölch Niklaus, Bektas Rima Nadine

机构信息

Section of Anesthesiology, Department of Clinical Diagnostics and Services, University of Zurich, Zurich, Switzerland.

Section of Neurology, Clinic of Small Animals, University of Zurich, Zurich, Switzerland.

出版信息

Front Vet Sci. 2023 Jan 6;9:1093267. doi: 10.3389/fvets.2022.1093267. eCollection 2022.

DOI:10.3389/fvets.2022.1093267
PMID:36686158
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9853535/
Abstract

INTRODUCTION

In recent years ketamine has increasingly become the focus of multimodal emergency management for epileptic seizures. However, little is known about the effect of ketamine on brain metabolites in epileptic patients. Magnetic resonance spectroscopy (MRS) is a non-invasive technique to estimate brain metabolites . Our aim was to measure the effect of ketamine on thalamic metabolites in idiopathic epileptic (IE) dogs using 3 Tesla MRS. We hypothesized that ketamine would increase the glutamine-glutamate (GLX)/creatine ratio in epileptic dogs with and without antiseizure drug treatment, but not in control dogs. Furthermore, we hypothesized that no different responses after ketamine administration in other measured brain metabolite ratios between the different groups would be detected.

METHODS

In this controlled prospective experimental trial IE dogs with or without antiseizure drug treatment and healthy client-owned relatives of the breeds Border Collie and Greater Swiss Mountain Dog, were included. After sedation with butorphanol, induction with propofol and maintenance with sevoflurane in oxygen and air, a single voxel MRS at the level of the thalamus was performed before and 2 min after intravenous administration of 1 mg/kg ketamine. An automated data processing spectral fitting linear combination model algorithm was used to estimate all commonly measured metabolite ratios. A mixed ANOVA with the independent variables ketamine administration and group allocation was performed for all measured metabolites. A < 0.05 was considered statistically significant.

RESULTS

Twelve healthy control dogs, 10 untreated IE and 12 treated IE dogs were included. No significant effects for GLX/creatine were found. However, increased glucose/creatine ratios were found ( < 0.001) with no effect of group allocation. Furthermore, increases in the GABA/creatine ratio were found in IEU dogs.

DISCUSSION

MRS was able to detect changes in metabolite/creatine ratios after intravenous administration of 1 mg/kg ketamine in dogs and no evidence was found that excitatory effects are induced in the thalamus. Although it is beyond the scope of this study to investigate the antiseizure potential of ketamine in dogs, results of this research suggest that the effect of ketamine on the brain metabolites could be dependent on the concentrations of brain metabolites before administration.

摘要

引言

近年来,氯胺酮越来越成为癫痫发作多模式急救管理的焦点。然而,关于氯胺酮对癫痫患者脑代谢物的影响知之甚少。磁共振波谱(MRS)是一种估计脑代谢物的非侵入性技术。我们的目的是使用3特斯拉MRS测量氯胺酮对特发性癫痫(IE)犬丘脑代谢物的影响。我们假设氯胺酮会增加接受和未接受抗癫痫药物治疗的癫痫犬的谷氨酰胺-谷氨酸(GLX)/肌酸比值,但对对照犬不会。此外,我们假设在不同组之间,氯胺酮给药后其他测量的脑代谢物比值不会有不同反应。

方法

在这项对照前瞻性实验试验中,纳入了接受或未接受抗癫痫药物治疗的IE犬以及边境牧羊犬和大瑞士山地犬品种的健康客户拥有的亲属。在用布托啡诺镇静、丙泊酚诱导并在氧气和空气中用七氟醚维持后,在静脉注射1mg/kg氯胺酮前和注射后2分钟,在丘脑水平进行单像素MRS。使用自动数据处理光谱拟合线性组合模型算法来估计所有常用测量的代谢物比值。对所有测量的代谢物进行了以氯胺酮给药和组分配为自变量的混合方差分析。P<0.05被认为具有统计学意义。

结果

纳入了12只健康对照犬、10只未治疗的IE犬和12只治疗的IE犬。未发现GLX/肌酸有显著影响。然而,发现葡萄糖/肌酸比值增加(P<0.001),且不受组分配的影响。此外,在IE犬中发现GABA/肌酸比值增加。

讨论

MRS能够检测犬静脉注射1mg/kg氯胺酮后脑代谢物/肌酸比值的变化,且未发现丘脑有兴奋作用的证据。虽然研究氯胺酮在犬中的抗癫痫潜力超出了本研究的范围,但本研究结果表明,氯胺酮对脑代谢物的影响可能取决于给药前脑代谢物的浓度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a786/9853535/1406ae34ada6/fvets-09-1093267-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a786/9853535/249a307310b4/fvets-09-1093267-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a786/9853535/1406ae34ada6/fvets-09-1093267-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a786/9853535/249a307310b4/fvets-09-1093267-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a786/9853535/1406ae34ada6/fvets-09-1093267-g0002.jpg

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