MYOCYTE CELLULAR HYPERPLASIA AND MYOCYTE CELLULAR HYPERTROPHY CONTRIBUTE TO CHRONIC VENTRICULAR REMODELING IN CORONARY-ARTERY NARROWING-INDUCED CARDIOMYOPATHY IN RATS

To determine whether cardiac failure produced by chronic coronary arte ry stenosis was associated with the activation of myocyte cellular hyp erplasia in the myocardium, the changes in number and size of left ven tricular myocytes were measured in rats 3 months after surgery. The hy pertrophied left ventricle was found to possess 44%, 32%, 49%, and 48% fewer mononucleated, binucleated, trinucleated, and tetranucleated my ocytes, respectively. In contrast, the hypertrophied right ventricle c ontained 1.49x10(6) more myocytes as a result of a 2.1-fold, 1.4-fold, and 1.4-fold increase in mononucleated, binucleated, and tetranucleat ed myocytes. Myocyte cell volume was seen to increase 49% and 21% in l eft and right ventricular myocytes, respectively. The process of myocy te cellular hyperplasia in the right ventricular myocardium was accomp anied by capillary proliferation, and these events were responsible fo r the parallel addition of newly formed cells and capillaries within t he wall and mural thickening. Moreover, the in-series insertion of new myocytes contributed to right ventricular dilation after coronary art ery stenosis. In view of the fact that extensive myocardial damage and cell loss may have masked the phenomenon of myocyte cellular hyperpla sia in the left ventricle, the presence of DNA synthesis in myocyte nu clei was evaluated at 3 days, 1 week, 2 weeks, 1 month, and 3 months a fter coronary artery stenosis. Bromodeoxyuridine (BrdU) labeling marke dly increased in myocyte nuclei of both ventricles, reaching its peak at 1 and 2 weeks. BrdU labeling of nonmyocyte nuclei also increased bu t mostly at 2 weeks. To exclude that DNA synthesis was not coupled wit h ploidy formation, ploidy classes in myocytes were measured by flow c ytometry and found not to be increased at 3 months after coronary arte ry narrowing in both ventricles. In addition, it was documented that m itosis occurred in myocytes and that this process was not associated w ith a change in the number of nuclei in myocytes. In conclusion, myocy te loss, myocyte cellular hypertrophy, and myocyte cellular hyperplasi a all contribute to the development of the cardiomyopathic heart of is chemic origin. (Circ Res. 1994;74:383-400.)