Romero L, Carbonell B, Trenor B, Rodriguez B, Saiz J, Ferrero J M
Universidad Politécnica de Valencia (I3BH), Spain.
Annu Int Conf IEEE Eng Med Biol Soc. 2010;2010:3253-6. doi: 10.1109/IEMBS.2010.5627230.
Experimental studies of pro-arrhythmic mechanisms are scarcely performed in humans due to the limited availability of human cardiomyocytes. Subsequently, extrapolation of animal experimental research to humans is widely extended. Our aim is to systematically compare the ionic mechanisms of the main cellular biomarkers of arrhythmic risk between human and rabbit using computer simulations. For this purpose four stimulation protocols were applied to the Mahajan et al. rabbit ventricular action potential (AP) model for control conditions and for ± 15 and ± 30% variations in the ionic current conductances of the main repolarization currents to quantify cellular biomarkers. Sensitivity of every simulated biomarker to every parameter modification was compared to that obtained for human in our previous work. Our results show that the ionic mechanisms involved in AP triangulation, systolic intracellular calcium concentration and AP duration (APD) accommodation to abrupt changes of pacing rate are very similar in both species. Unfortunately, significant differences were found in the ionic mechanisms related to APD, restitution properties and rate dependence of intracellular calcium and sodium concentrations. In conclusion, extrapolation of experimental research in rabbit to humans is limited by the existence of species dependent ionic mechanisms. In addition, this analysis is very useful for understanding and improvement of mathematical models.
由于人类心肌细胞的可获得性有限，很少在人体上进行促心律失常机制的实验研究。随后，动物实验研究向人类的外推得到了广泛应用。我们的目的是使用计算机模拟系统地比较人和兔心律失常风险主要细胞生物标志物的离子机制。为此，将四种刺激方案应用于Mahajan等人的兔心室动作电位（AP）模型，用于对照条件以及主要复极电流的离子电流电导±15%和±30%变化的情况，以量化细胞生物标志物。将每个模拟生物标志物对每个参数修改的敏感性与我们之前工作中在人体上获得的敏感性进行比较。我们的结果表明，在这两个物种中，AP三角化、收缩期细胞内钙浓度和AP持续时间（APD）对起搏速率突然变化的适应性所涉及的离子机制非常相似。不幸的是，在与APD、复极特性以及细胞内钙和钠浓度的速率依赖性相关的离子机制中发现了显著差异。总之，兔实验研究向人类的外推受到物种依赖性离子机制存在的限制。此外，这种分析对于理解和改进数学模型非常有用。
