Eccentric cardiac hypertrophy

Molecular Phenotypes of Concentric and Eccentric Cardiac Hypertrophy... 

J-L. Inactivation of focal adhesion kinase in cardiomyocytes promotes eccentric cardiac hypertrophy and fibrosis in mice. J. 

When the primary stimulus to hypertrophy is exercise, the intermittent diastolic load imposed on the heart leads to an eccentric pattern of cardiac hypertrophy with enhanced cardiac function (Anversa et al. 1983, 1986 Moore et al. 1993 Jin... 

Fig. 12.1 Concentric and eccentric cardiac remodeling. In response to a systolic load, newly formed sarcomeres will be assembled in a parallel fashion leading to an increase in myocyte cell width. This mode of sarcomere assembly will result in a concentric pattern of cardiac hypertrophy characterized by an increase in wall thickness and reduction in chamber volume. In contrast, in response to a diastolic load, newly formed sarcomeres will be assembled in an in series pattern leading to an increase in myocyte cell length. This mode of sarcomere assembly will promote an eccentric pattern of cardiac hypertrophy characterized primarily by an increase in chamber volume. However, a modest increase in wall thickness will also occur because of the secondary increase in systolic wall stress associated with eccentric remodeling.

Gq- and phosphatidylinositol 3-kinase-dependent signaling pathways have been linked to the hypertrophic growth of cardiac myocytes. Data highlighting their involvement were reported in numerous in vivo and in vitro studies employing both pharmacological and transgenic approaches. The following section will attempt to summarize their relative role in eccentric and concentric cardiac hypertrophy. 

Pathological cardiac hypertrophy develops in response to stresses, and can be concentric, eccentric, or both. An excess pressure load placed on the heart, for example, resulting from uncorrected hypertension or valvular disease, results in concentric hypertrophy. This hypertrophy is initially believed to be adaptive, normalizing systolic wall stress, though it is not clear that hypertrophy is necessary to maintain systolic function in the face of moderately elevated pressure loads. Eccentric hypertrophy results most often from volume loads such as those in valvular insufficiency. Einally, the hypertrophy that occurs in the remote noninfarcted myocardium, as part of the remodeling process following a myocardial infarction, may be both concentric and eccentric. 

The above model was further employed to study observed patterns of cardiac hypertrophy. First, the initial size of the ventricle was consistent with that of a normal dog. Second, a pressure overload was created by raising mean aortic pressure. The model was then used to recompute ventricular size for the new afterload condition. Results show the classic wall thickening and increased wall thickness-to-diameter ratio (W/D), consistent with observed concentric hypertrophy. Third, volume overload was imposed by elevating cardiac output. In this case, the model predicted an increase in diameter with relatively little increase in the W/D ratio, referred to as eccentric hypertrophy. Lastly, the sarcomere function was impaired and its effect on the ventricle evaluated. An eccentric form of hypertrophy resulted. The diameter-to-length... 

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