Hamlin Robert L
Department of Veterinary Biosciences, The Ohio State University, OH, USA.
Pharmacol Ther. 2007 Feb;113(2):276-95. doi: 10.1016/j.pharmthera.2006.08.006. Epub 2006 Sep 16.
Limitations in understanding of arrhythmias stem from lack of animal models which serve as surrogates for man. The purpose of this review is to discuss iatrogenic and naturally occurring animal models that are useful in our understanding of the mechanisms of ventricular arrhythmia and of antiarrhythmic and proarrhythmic agents. It is not surprising however that some information obtained from studies on infrahuman mammals may not be extrapolated to man. Need for anesthesia affects profoundly the electrophysiology of the heart, including autonomic affects. Most of the animal are modification of the Harris' 2-stage model. A model proposed by Schwartz, Billman and Stone has evolved as one that produces arguably the most information on the pathophysiology of arrhythmia production, including the role of the autonomic nervous system and the interaction with pharmacological agents. Intoxication with digitalis and escalating doses of epinephrine are commonly used models for production of ventricular arrhythmias. No matter what model of ventricular arrhythmias is used, programmed electrical stimulation can be useful to uncover increased tendency for arrhythmia, even if no arrhythmia occurs spontaneously. Models of spontaneous ventricular arrhythmia occur in German shepherd puppies, Boxer dogs, Doberman pinchers with dilated cardiomyopathy, and in large dogs with gastric dilatation or splenic torsion. Models are necessary because they allow for controlled studies and methods of exploration impossible, for legal and ethical reasons, in humans. Nonetheless, ethical considerations in using animal models are still important, and there is a continual search for non-animal models to explore ventricular arrhythmias.
对心律失常认识的局限性源于缺乏可作为人类替代物的动物模型。本综述的目的是讨论医源性和自然发生的动物模型,这些模型有助于我们理解室性心律失常的机制以及抗心律失常和促心律失常药物。然而,从对非人类哺乳动物的研究中获得的一些信息可能无法外推至人类,这并不奇怪。麻醉需求会深刻影响心脏的电生理学,包括自主神经的影响。大多数动物模型是对哈里斯两阶段模型的改良。施瓦茨、比尔曼和斯通提出的一个模型逐渐发展成为一个能产生关于心律失常发生病理生理学最多信息的模型,包括自主神经系统的作用以及与药物的相互作用。洋地黄中毒和递增剂量的肾上腺素是常用的室性心律失常模型。无论使用何种室性心律失常模型,程控电刺激都有助于发现心律失常倾向增加的情况,即使没有自发心律失常发生。自发性室性心律失常模型见于德国牧羊犬幼犬、拳师犬、患有扩张型心肌病的杜宾犬以及患有胃扩张或脾扭转的大型犬。模型是必要的,因为它们能进行在人类中因法律和伦理原因而无法进行的对照研究和探索方法。尽管如此,使用动物模型时的伦理考量仍然很重要,并且一直在寻找非动物模型来探索室性心律失常。