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α受体拮抗剂瓦替诺昔不能消除右美托咪定对马小肠实验性缺血再灌注损伤的预处理作用。

Alpha Antagonist Vatinoxan Does Not Abolish the Preconditioning Effect of Dexmedetomidine on Experimental Ischaemia-Reperfusion Injury in the Equine Small Intestine.

作者信息

Verhaar Nicole, Kopp Veronika, Pfarrer Christiane, Neudeck Stephan, König Kathrin, Rohn Karl, Kästner Sabine

机构信息

Clinic for Horses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.

Institute for Anatomy, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.

出版信息

Animals (Basel). 2023 Aug 30;13(17):2755. doi: 10.3390/ani13172755.

Abstract

Pharmacological preconditioning with dexmedetomidine has been shown to ameliorate intestinal ischaemia reperfusion injury in different species, including horses. However, it remains unknown if this effect is related to alpha adrenoreceptor activity. Therefore, the aim of this study was to determine the effect of dexmedetomidine preconditioning with and without the administration of the peripheral alpha antagonist vatinoxan. This prospective randomized experimental trial included 12 horses equally divided between two treatment groups. Horses in group Dex received a bolus of dexmedetomidine followed by a continuous rate infusion (CRI), while group DexV additionally received vatinoxan as bolus and CRI. A median laparotomy was performed under general anaesthesia, and jejunal ischaemia was applied for 90 min, followed by 30 min of reperfusion. Mucosal damage was evaluated in full thickness biopsies by use of a semiquantitative mucosal injury score and by determining the apoptotic cell counts with immunohistochemical staining for cleaved caspase-3 and TUNEL. Comparisons between the groups and time points were performed using non-parametric tests ( < 0.05). During pre-ischaemia and ischaemia, no differences could be found in mucosal injury between the groups. After reperfusion, group DexV showed lower mucosal injury scores compared to group Dex. The apoptotic cell counts did not differ between the groups. In conclusion, antagonizing the peripheral alpha adrenoreceptors did not negatively affect dexmedetomidine preconditioning.

摘要

已证明右美托咪定进行药理学预处理可改善包括马在内的不同物种的肠缺血再灌注损伤。然而,这种作用是否与α肾上腺素能受体活性有关仍不清楚。因此,本研究的目的是确定右美托咪定预处理在给予和不给予外周α拮抗剂瓦替诺昔的情况下的效果。这项前瞻性随机试验纳入了12匹马,平均分为两个治疗组。Dex组的马先给予一剂右美托咪定,然后持续输注(CRI),而DexV组额外给予瓦替诺昔作为推注和CRI。在全身麻醉下进行正中剖腹术,对空肠进行90分钟的缺血处理,随后再灌注30分钟。通过使用半定量黏膜损伤评分并通过免疫组织化学染色检测裂解的半胱天冬酶-3和TUNEL来确定凋亡细胞计数,从而在全层活检中评估黏膜损伤。使用非参数检验进行组间和时间点的比较(<0.05)。在缺血前和缺血期间,两组之间的黏膜损伤没有差异。再灌注后,DexV组的黏膜损伤评分低于Dex组。两组之间的凋亡细胞计数没有差异。总之,拮抗外周α肾上腺素能受体不会对右美托咪定预处理产生负面影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0d6/10486550/3b5f25eeaa49/animals-13-02755-g001.jpg

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