Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Int J Cardiol. 2011 Apr 14;148(2):154-60. doi: 10.1016/j.ijcard.2009.10.047. Epub 2009 Nov 17.
Both dilated (DCM) and ischemic cardiomyopathy (ICM) are associated with action potential (AP) prolongation due to ionic remodeling. In humans, AP prolongation is more pronounced in myocytes isolated from explanted DCM than ICM hearts. However, there is a large variability due to confounding factors, including age, sex, concomitant disease, drug treatment, and progression of the disease at the time of heart transplantation. Here, we investigated the etiology-dependency of ionic remodeling in standardized rabbit models of ICM and DCM.
ICM and DCM were induced by chronic infarction or combined volume and pressure overload, respectively. APs and membrane currents were measured using patch-clamp methodology.
Both ICM and DCM caused hypertrophy, but this hypertrophy was more prominent in DCM rabbits that also developed heart failure (DCM(F)), as revealed by the presence of ascites. Animals of either model showed AP prolongation. While the AP prolongation was similar by the same degree of hypertrophy, AP prolongation in DCM(F) was more pronounced. In all models, L-type Ca(2+) current, inward rectifier K(+) current, and rapid delayed rectifier K(+) current were unaltered, but the transient outward K(+) current (I(to 1)) density was significantly reduced. The I(to 1) decrease was not associated with differences in voltage-dependency of (in)activation. I(to 1) downregulation was similar in ICM and DCM with the same degree of hypertrophy, but was more pronounced in DCM(F).
The amount of ionic remodeling and AP prolongation in cardiomyopathic rabbits is due to differences in the amount of hypertrophy rather than differences in the etiology of the cardiomyopathy.
扩张型心肌病（DCM）和缺血性心肌病（ICM）都与离子重构导致动作电位（AP）延长有关。在人类中，从扩张型 DCM 心脏移植的心肌细胞中分离出的心肌细胞中，AP 延长更为明显。然而，由于混杂因素（包括年龄、性别、并存疾病、药物治疗以及心脏移植时疾病的进展），存在很大的变异性。在这里，我们研究了在标准化兔 ICM 和 DCM 模型中离子重构的病因依赖性。
通过慢性梗塞或容积和压力超负荷的联合作用分别诱导 ICM 和 DCM。使用膜片钳技术测量 AP 和膜电流。
ICM 和 DCM 均导致心肌肥厚，但 DCM 兔（即 DCM(F)）的心肌肥厚更为明显，因为有腹水的存在。两种模型的动物均表现出 AP 延长。虽然 AP 延长程度相同，但 DCM(F)的 AP 延长更为明显。在所有模型中，L 型 Ca(2+)电流、内向整流钾电流和快速延迟整流钾电流均无改变，但瞬时外向钾电流（I(to 1)）密度显著降低。I(to 1)的减少与（失）活的电压依赖性差异无关。DCM(F)的 I(to 1)下调与 ICM 和 DCM 相同程度的肥厚相关，但更为明显。
在心肌病兔中，离子重构和 AP 延长的程度取决于肥厚的程度，而不是心肌病的病因。
