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一氧化氮在氯胺酮/赛拉嗪对大鼠急性心脏缺血再灌注模型抗心律失常作用中的作用。

The role of nitric oxide on the antiarrhythmic effects of ketamine/xylazine in a rat model of acute cardiac ischemia-reperfusion.

作者信息

Imani Alireza, Rajani Sulail Fatima, Rakhshan Kamran, Faghihi Mahdieh, Nemati Masoumeh, Parsazadegan Tanaz

机构信息

Electrophysiology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Curr Res Physiol. 2022 Jul 12;5:302-311. doi: 10.1016/j.crphys.2022.06.008. eCollection 2022.

DOI:10.1016/j.crphys.2022.06.008
PMID:35856058
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9287742/
Abstract

The prevalence of ventricular arrhythmias during general anesthesia is about 70%. In experimental studies on the antiarrhythmic effects of different agents, using anesthetic drugs that do not have any protective properties are preferable. The present study was conducted to investigate molecular mechanisms involved in the antiarrhythmic effects of ketamine/xylazine (K/X). Sixty male rats were assigned to eight groups: K/X, L -NAME (25-35 mg/kg) with thiopental (TP), L-NAME (25-35 mg/kg) with ketamine/xylazine, L arginine (100 mg/kg) with thiopental, L-arginine (100 mg/kg) with ketamine/xylazine. After anesthetic induction using TP or K/X, the animals were subjected to 30 min of ischemia. Hemodynamic parameters, ventricular arrhythmias during ischemia, the incidence of ventricular tachycardia (VT), and ventricular fibrillation (VF) were measured. Additionally, in order to assess nitrite/nitrate ratio and LDH after ischemia, serum samples were collected and used. Our results showed that in the K/X group, the number of VT and VF, duration of VT (p = 0.006), the severity of arrhythmias (p = 0.0179). There was no VF incidence in this group. These protective effects were faded by administration of L-NAME with K/X. The combination of L- Arginine in the TP group decreased the number and duration of VT (p < 0.001, p = 0.0013) with no incidence of VF in comparison with TP. L-arginine with K/X groups increased the number and duration of VT (p < 0.0001, p < 0.001) compared to K/X and VF was seen (100%). However, there was no significant difference between TP and K/X groups in terms of this nitrite/nitrate ratio. These findings suggest that the antiarrhythmic effects of ketamine/xylazine might be partially relative to the nitric oxide synthesis pathway.

摘要

全身麻醉期间室性心律失常的发生率约为70%。在关于不同药物抗心律失常作用的实验研究中,使用不具有任何保护特性的麻醉药物更为可取。本研究旨在探讨氯胺酮/赛拉嗪(K/X)抗心律失常作用的分子机制。60只雄性大鼠被分为8组:K/X组、L - NAME(25 - 35mg/kg)与硫喷妥钠(TP)组、L - NAME(25 - 35mg/kg)与氯胺酮/赛拉嗪组、L - 精氨酸(100mg/kg)与硫喷妥钠组、L - 精氨酸(100mg/kg)与氯胺酮/赛拉嗪组。使用TP或K/X进行麻醉诱导后,对动物进行30分钟的缺血处理。测量血流动力学参数、缺血期间的室性心律失常、室性心动过速(VT)的发生率和心室颤动(VF)。此外,为了评估缺血后的亚硝酸盐/硝酸盐比值和乳酸脱氢酶,收集并使用血清样本。我们的结果表明,在K/X组中,VT和VF的数量、VT的持续时间(p = 0.006)、心律失常的严重程度(p = 0.0179)。该组无VF发生。用L - NAME与K/X联合给药可使这些保护作用减弱。与TP组相比,TP组中L - 精氨酸的联合使用减少了VT的数量和持续时间(p < 0.001,p = 0.0013),且无VF发生。与K/X组相比,L - 精氨酸与K/X组增加了VT的数量和持续时间(p < 0.0001,p < 0.001),且可见VF(100%)。然而,在亚硝酸盐/硝酸盐比值方面,TP组和K/X组之间没有显著差异。这些发现表明,氯胺酮/赛拉嗪的抗心律失常作用可能部分与一氧化氮合成途径有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e8e/9287742/d030c879a15e/gr10.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e8e/9287742/a1111f8d5d0e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e8e/9287742/38220345ccad/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e8e/9287742/ac9436db1f55/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e8e/9287742/fbb4f54509f8/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e8e/9287742/b9967ad2f784/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e8e/9287742/742a3469fb4c/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e8e/9287742/ee4999fb65f1/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e8e/9287742/e7453bcd051f/gr8.jpg
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