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新型抗心律失常药物的发现:动物模型的研究进展。

New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.

机构信息

NIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, Rajasthan, 303121, India.

Medley Pharmaceuticals Ltd., Formulation R&D, Mumbai, 400059, India.

出版信息

Sci Rep. 2023 Sep 29;13(1):16420. doi: 10.1038/s41598-023-41942-4.

Abstract

Cardiac rhythm regulated by micro-macroscopic structures of heart. Pacemaker abnormalities or disruptions in electrical conduction, lead to arrhythmic disorders may be benign, typical, threatening, ultimately fatal, occurs in clinical practice, patients on digitalis, anaesthesia or acute myocardial infarction. Both traditional and genetic animal models are: In-vitro: Isolated ventricular Myocytes, Guinea pig papillary muscles, Patch-Clamp Experiments, Porcine Atrial Myocytes, Guinea pig ventricular myocytes, Guinea pig papillary muscle: action potential and refractory period, Langendorff technique, Arrhythmia by acetylcholine or potassium. Acquired arrhythmia disorders: Transverse Aortic Constriction, Myocardial Ischemia, Complete Heart Block and AV Node Ablation, Chronic Tachypacing, Inflammation, Metabolic and Drug-Induced Arrhythmia. In-Vivo: Chemically induced arrhythmia: Aconitine antagonism, Digoxin-induced arrhythmia, Strophanthin/ouabain-induced arrhythmia, Adrenaline-induced arrhythmia, and Calcium-induced arrhythmia. Electrically induced arrhythmia: Ventricular fibrillation electrical threshold, Arrhythmia through programmed electrical stimulation, sudden coronary death in dogs, Exercise ventricular fibrillation. Genetic Arrhythmia: Channelopathies, Calcium Release Deficiency Syndrome, Long QT Syndrome, Short QT Syndrome, Brugada Syndrome. Genetic with Structural Heart Disease: Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia, Dilated Cardiomyopathy, Hypertrophic Cardiomyopathy, Atrial Fibrillation, Sick Sinus Syndrome, Atrioventricular Block, Preexcitation Syndrome. Arrhythmia in Pluripotent Stem Cell Cardiomyocytes. Conclusion: Both traditional and genetic, experimental models of cardiac arrhythmias' characteristics and significance help in development of new antiarrhythmic drugs.

摘要

心脏的节律受心脏的微观和宏观结构调节。起搏器异常或电传导中断会导致心律失常,可能是良性、典型、威胁性、最终致命的,在临床实践中发生,患者正在使用洋地黄、麻醉或急性心肌梗死。传统和遗传动物模型包括:

  • 体外:分离的心室肌细胞、豚鼠乳头肌、膜片钳实验、猪心房肌细胞、豚鼠心室肌细胞、豚鼠乳头肌:动作电位和不应期,Langendorff 技术,乙酰胆碱或钾引起的心律失常。

  • 获得性心律失常障碍:横主动脉缩窄、心肌缺血、完全性心脏阻滞和房室结消融、慢性快起搏、炎症、代谢和药物诱导的心律失常。

  • 体内:化学诱导的心律失常:乌头碱拮抗作用、地高辛诱导的心律失常、哇巴因/哇巴因诱导的心律失常、肾上腺素诱导的心律失常和钙诱导的心律失常。

  • 电诱导的心律失常:心室颤动电阈值、通过程控电刺激的心律失常、狗的突发性冠状动脉死亡、运动性心室颤动。

  • 遗传性心律失常:通道病、钙释放缺陷综合征、长 QT 综合征、短 QT 综合征、Brugada 综合征。

  • 遗传性与结构性心脏病:致心律失常性右心室心肌病/发育不良、扩张型心肌病、肥厚型心肌病、心房颤动、窦房结疾病、房室传导阻滞、预激综合征。

  • 多能干细胞心肌细胞中的心律失常。

结论

传统和遗传的心律失常实验模型的特征和意义有助于开发新的抗心律失常药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18dc/10541452/18f0086168aa/41598_2023_41942_Fig1_HTML.jpg

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