In-vivo models of arrhythmias: a canine model of sudden cardiac death
In-vivo models of arrhythmias: a canine model of sudden cardiac death
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DOI：
10.1007/3-540-26574-0_7
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发表时间：
2005-01-01
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影响因子：
--
通讯作者：
Billman, GE
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作者：
Billman, GE
在大多数工业发达国家，室性心动过速引起的心源性猝死仍然是死亡的主要原因，在美国每年造成30万至50万人死亡（Zipes和Wellens， 1998年）。然而，尽管这一问题非常严重，但确定导致这些过早死亡的机制，以及开发安全有效的抗心律失常疗法，仍然难以捉摸。使用合适的室性心律失常动物模型是至关重要的，这不仅是为了发现引发致命性心律失常的机制，也是为了对潜在的抗心律失常药物进行临床前评估。所使用的模型必须尽可能地模拟最常与心源性猝死高风险相关的潜在病理状况。多年来，许多不同的动物被用于研究心室颤动的机制，并在临床前开发阶段评估抗心律失常药物。所使用的模型有不同的优点和缺点，并取得了不同程度的成功。最近对许多这些模型进行了详细的分析和比较（Billman 2002； Study Group on Experimental心律失常研究1995），因此，本章将不进行讨论。本章将仅限于详细描述制备犬心源性猝死模型的方法，该模型已被证明在识别导致心室颤动的因素以及评估潜在的抗心律失常治疗方面都是有用的。
Sudden cardiac death resulting from ventricular tachyarrhythmias remains the major cause of death in most industrially developed countries, accounting for between 300,000 and 500,000 deaths each year in the United States (Zipes and Wellens 1998). Yet despite the enormity of this problem, the identification of the mechanisms responsible for these untimely deaths, as well as the development of safe and effective antiarrhythmic therapies, remains elusive. The use of appropriate animal models of ventricular arrhythmias is critical, not only for discovering the mechanisms that trigger lethal cardiac rhythm disorders, but also for the preclinical evaluation of potential anti-arrhythmic drugs. The model used must mimic, as closely as possible, the underlying pathological conditions most often associated with a high risk of sudden cardiac death. Over the years, a number of different animals have been used to investigate the mechanisms responsible for ventricular fibrillation and to assess anti-arrhythmic medications during the preclinical stage of development. The models used have different strengths and weaknesses and have had varying degrees of success. A detailed analysis and comparison of many of these models has recently been reviewed (Billman 2002; Study Group on Experimental Arrhythmia Research 1995) and, as such, will not be discussed in the present chapter. The present chapter will be limited to a detailed description of methods to prepare a canine model of sudden cardiac death that has proven useful in both the identification of factors contributing to ventricular fibrillation, as well as the evaluation of potential anti-arrhythmic therapies.