THE CELLULAR BASIS OF PACING-INDUCED DILATED CARDIOMYOPATHY - MYOCYTECELL LOSS AND MYOCYTE CELLULAR REACTIVE HYPERTROPHY

Background Rapid ventricular pacing leads to a cardiac myopathy consis ting of an increase in chamber dimension, mural thinning, elevation in ventricular wall stress, and congestive heart failure, mimicking dila ted cardiomyopathy in humans. However, contrasting results have been o btained concerning the mechanisms of ventricular dilation and the exis tence of myocardial hypertrophy. Moreover, questions have been raised regarding the occurrence of myocardial damage and cell loss in the dev elopment of the experimental myopathy. Methods and Results The functio nal and structural characteristics of the heart were studied in consci ous dogs subjected to left ventricular pacing at 210 beats per minute for 3 weeks and 240 beats per minute for an additional week. At the ti me the animals were killed, measurements of myocardial structural inte grity and myocyte shape, size, and number were determined by morphomet ric analysis of the myocardium in situ and enzymatically dissociated c ells. The experimental protocol used was associated with overt cardiac failure documented by an increase in left ventricular end-diastolic p ressure and a decrease in left ventricular systolic pressure and +dP/d t in combination with tachycardia, ascites, and pulmonary congestion. Although cardiac weights were not altered, cavitary diameter was incre ased and wall thickness was decreased from the base to the apex of the heart. Multiple foci of replacement fibrosis, comprising 6% of the my ocardium, were detected across the left ventricular wall. Measurements of myocyte size and number documented a 39% loss of cells in the enti re ventricle and a 61% increase in volume of the remaining viable myoc ytes. Myocyte hypertrophy was characterized by a 33% increase in cell length and a 23% increase in transverse area, resulting in a 23% incre ase in the cell length-to-cell diameter ratio. Pacing did not alter th e relative proportion of mononucleated, binucleated, and multinucleate d myocytes in the myocardium. Conclusions Myocyte cell loss and myocyt e reactive hypertrophy are the major components of ventricular remodel ing in pacing-induced dilated cardiomyopathy.