MYOCYTE CELLULAR HYPERTROPHY IS RESPONSIBLE FOR VENTRICULAR REMODELING IN THE HYPERTROPHIED HEART OF MIDDLE-AGED INDIVIDUALS IN THE ABSENCEOF CARDIAC-FAILURE

Objective: The aim was to measure changes in the numbers and size of v entricular myocytes in human hearts with marked ventricular hypertroph y and no clear signs of cardiac failure, to determine whether myocyte cellular hypertrophy is the only factor involved in the increase in ca rdiac mass. Methods: Morphometric techniques were applied to estimate the number of myocyte nuclei per unit volume of myocardium which, in c ombination with the determination of the volume percent of myocytes, a llowed the computation of the average myocyte cell volume per nucleus and total number of myocyte nuclei in the ventricles. Subsequently, th e volume fraction of replacement fibrosis in the tissue was assessed a nd absolute component volumes in the ventricles obtained. Results: Eig ht hypertrophied human hearts, weight 561(SD 68) g, were collected at necropsy from hypertensive patients who died from non-cardiac causes a nd were compared with eight normal hearts, weight 387(37) g, obtained from healthy individuals who also died from non-cardiac causes. With c ardiac hypertrophy, left and right ventricular weight increased by 53% and 57%, whereas myocyte cell volume increased by 112% and 84%, respe ctively. The disproportion between the increase in ventricular weight and the increase in myocyte volume was due to a 30% and 16% loss in le ft and right ventricular myocytes following hypertensive hypertrophy. Myocyte loss also provoked a 319% and a 188% increase in the amount of replacement fibrosis in the left and right ventricular myocardium. Th ese tissue and cellular processes resulted in an expansion in ventricu lar mass which exceeded the thickening of the wall so that an increase in cavitary volume occurred in both ventricles. Conclusions: Myocyte cellular hypertrophy is responsible for ventricular hypertrophy in hyp ertensive cardiomyopathy in its compensated stage. Myocyte loss preced es the impairment in ventricular pump function and may be implicated i n the initiation of ventricular maladaptation.