STRUCTURAL REMODELING AND MECHANICAL DYSFUNCTION OF CARDIAC MYOCYTES IN HEART-FAILURE

End stage heart failure due to ischemic (ICM) or dilated (DCM) cardiom yopathy is characterized by a dilated, relatively thin-walled ventricl e. The hypothesis has been proposed that the structural basis of ventr icular expansion is due to side-to-side slippage of myocytes within th e wall. Although this represents one potential mechanism for the obser ved phenomena of chamber dilatation and subsequent wall thinning, the degree of slippage claimed is not necessarily in harmony with the magn itude of chamber enlargement and mural thinning. Moreover, sarcomere e xtension was not examined in the base to the apical regions of the hea rt, leaving open the question as to the role of changes in resting sar comere length in acute chamber dilatation. In this regard, an alternat ive etiology for the detrimental cardiac architectural rearrangement s een in dilated failure can be supplied by postulating the occurrence o f maladaptive remodeling of cardiac myocyte morphology. In this model, myocytes increase in length by an increase in the number of sarcomere s in series, thus increasing chamber diameter in an attempt to maintai n cardiac output. However, these cells do not enlarge to any significa nt degree in the transverse diameter preventing the heart from develop ing adequate force. This hypothesis is supported by recent evidence fr om patients with ICM and DCM indicating that myocyte lengthening alone could account for all the dilatation observed. Furthermore, it appear s that the thinning of the ventricular wall in failure is due to inade quate transverse growth of cardiac myocytes coupled with scattered myo cyte cell loss throughout the ventricular wall. The ultimate consequen ce is that the ratio of myocyte length to myocyte width is increased i n heart failure. Evidence also indicates that these long, slender myoc ytes have a reduced ability to shorten and/or develop adequate force t o compensate for the extent of chamber dilation. Thus, differential my ocyte cell growth is postulated to be the primary event involved in th e pathological morphometric changes observed during dilated cardiac fa ilure. A molecular mechanism may be involved in the activation and exp ression of fetal or atrial genes controlling myocyte shape.