The cellular basis of dilated cardiomyopathy in humans

https://doi.org/10.1016/S0022-2828(08)80028-4Get rights and content

C. A. Beltrami, N. Finato, M. Rocco, G. A. Feruglio, C. Puricelli, E. Cigola, E. H. Sonnenblick, G. Olivetti, P. Anversa. The Cellular Basis of Dilated Cardiomyopathy in Humans. Journal of Molecular and Cellular Cardiology (1995) 27, 291–305. The present investigation was designed to evaluate whether end-stage cardiac failure in patients affected by dilated cardiomyopathy (DC) was dependent upon extensive myocyte cell death with reduction in muscle mass or was the consequence of collagen accumulation in the myocardium independently from myocyte cell loss. In addition, the mechanisms of ventricular dilation were analysed in order to determine whether the changes in cardiac anatomy were important variables in the development of intractable congestive heart failure. DC is characterized by chamber dilation, myocardial scarring and myocyte hypertrophy in the absence of significant coronary atherosclerosis. However, the relative contribution of each of these factors to the remodeling of the ventricle is currently unknown. Moreover, no information is available concerning the potential etiology of collagen deposition in the myocardium and the changes in number and size of ventricular myocytes with this disease. Morphometric methodologies were applied to the analysis of 10 DC hearts obtained from patients undergoing cardiac transplantation. An identical number of control hearts was collected from individuals who died from cruises other than cardiovascular diseases. DC produced a 2.2-fold and 4.2-/bid increase in left ventricular weight and chamber vohnne resuking in a 48% reduction in mass-to-volume ratio. In the right ventricle, tissue weight and chamber size were both nearly doubled. Left ventricular dilation was the result of a 59% lengthening of myocytes and a 20% increase in the transverse circumference due to slippage of myocytes within the wall. Myocardial scarring represented by segmental, replacement and interstitial fibrosis occupied approximately 20% of each ventricle, and was indicative of extensive myocyte cell loss. However, myocyte number was not reduced and average cell volume increased 2-fold in both ventricles. In conclusion, reactive growth processes in myocytes and architectural rearrangement of the muscle compartment of the myocardium appear to be the major determinants of ventricular remodeling and the occurrence of cardiac failure in DC.

References (46)

  • MJ Zhao et al.

    Profound structural alterations of the extracellular collagen matrix in postischemic dysfunctioal (“stunned”) but viable myocardium

    J Am Coll Cardiol

    (1987)
  • CP Adler

    Polyploidization and augmentation of heart muscle cells during normal cardiac growth and in cardiac hypertrophy

  • CP Adler et al.

    Myocardial DNA content, ploidy level and cell number in geriatric hearts: post-mortem examinations of human myocardium in old age

    J Mol Cell Cardiol

    (1986)
  • CP Adler et al.

    Numerische Hyperplasie der Herzmuskelzellen bei Herzhypertrophie

    Dtsch Med Wochenschr

    (1971)
  • P Anversa et al.

    Morphometry of exercise-induced right ventricular hypertrophy in the rat

    Circ Res

    (1983)
  • P Anversa et al.

    Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart

    Circ Res

    (1990)
  • P Anversa et al.

    Cardiac hypertrophy and ventricular remodeling

    Lab Invest

    (1991)
  • P Anversa et al.

    Effects of hypertension and coronary constriction on cardiac function, morphology, and contractile proteins in rats

    Am J Physiol

    (1993)
  • P Anversa et al.

    Ischemic myocardial injury and ventricular remodeling

    Cadiovasc Res

    (1993)
  • P Anversa et al.

    Myocardial infarction, cardiac anatomy and ventricular loading

    Cadioscience

    (1993)
  • G Baroldi et al.

    The nuclear patterns of the cardiac muscle fiber

    Cardiologia

    (1967)
  • CA Beltrami et al.

    Structural basis of end stage failure in ischemic cardiomyopathy in humans

    Circulation

    (1994)
  • HT Dodge et al.

    Usefulness and limitation of radiographic methods for determining left ventricular volume

    Am J Cardiol

    (1966)
  • Cited by (236)

    View all citing articles on Scopus
    View full text