Luchner A, Borgeson D D, Grantham J A, Friedrich E, Riegger G A, Burnett J C, Redfield M M
Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, F.J. Strauss Allee 11, 93042 Regensburg, Germany.
Eur J Heart Fail. 2000 Dec;2(4):379-86. doi: 10.1016/s1388-9842(00)00104-5.
We have recently described a modified model of progressive rapid ventricular pacing-induced heart failure which evolves over a period of 38 days. To further characterize left ventricular remodeling during the progression of heart failure, we assessed left ventricular geometry, wall stress, and atrial natriuretic peptide (ANP) gene expression and protein content during control conditions, asymptomatic left ventricular dysfunction, and overt congestive heart failure (CHF). Although asymptomatic left ventricular dysfunction was characterized by a significant increase in systolic and diastolic left ventricular dimension (+30% and +6%, respectively, P<0.05 each) and a marked increase in left ventricular systolic wall stress (+68%, P<0.01), left ventricular ANP gene expression was unchanged as compared to control. In contrast, strong left ventricular ANP gene expression (+449%, P<0.05) was observed during overt CHF in the absence of further significant increases in left ventricular systolic wall stress. The onset of strong left ventricular ANP gene expression was associated with increased ANP content (+88%, P<0.05) and left ventricular mass index (+13%, P<0.05). In contrast, left atrial ANP gene expression and left ventricular diastolic wall stress increased progressively during asymptomatic left ventricular dysfunction (+39%, P=n.s. and +131%, P<0.01) and overt CHF (+76% and +336% vs. control, P<0.01 each). Progressive rapid ventricular pacing is associated with the induction of left ventricular ANP gene expression and protein synthesis exclusively during overt CHF. The current studies provide new insight into the temporal pattern of ANP-activation and the disparity between left ventricular systolic wall stress and ANP-activation in a large animal model of progressive CHF.
我们最近描述了一种改良的进行性快速心室起搏诱导的心力衰竭模型，该模型在38天内逐渐发展。为了进一步表征心力衰竭进展过程中的左心室重塑，我们评估了对照状态、无症状左心室功能障碍和明显充血性心力衰竭（CHF）期间的左心室几何形状、壁应力、心房利钠肽（ANP）基因表达和蛋白质含量。尽管无症状左心室功能障碍的特征是左心室收缩和舒张尺寸显著增加（分别增加30%和6%，P均<0.05）以及左心室收缩壁应力显著增加（增加68%，P<0.01），但与对照相比，左心室ANP基因表达未发生变化。相比之下，在明显CHF期间观察到左心室ANP基因强烈表达（增加449%，P<0.05），而左心室收缩壁应力没有进一步显著增加。左心室ANP基因强烈表达的开始与ANP含量增加（增加88%，P<0.05）和左心室质量指数增加（增加13%，P<0.05）相关。相比之下，在无症状左心室功能障碍（分别增加39%，P无统计学意义和增加131%，P<0.01）和明显CHF（与对照相比分别增加76%和336%，P均<0.01）期间，左心房ANP基因表达和左心室舒张壁应力逐渐增加。进行性快速心室起搏仅在明显CHF期间诱导左心室ANP基因表达和蛋白质合成。当前研究为在大型进行性CHF动物模型中ANP激活的时间模式以及左心室收缩壁应力与ANP激活之间的差异提供了新的见解。
