Modulation of cardiac myocyte beating rate and hypertrophy by cardiac fibroblasts isolated from neonatal rat ventricle.

We evaluated the in vitro modulation of cardiac myocyte beating rate and growth hypertrophy in the presence or absence of cardiac fibroblasts. Cardiac myocytes and fibroblasts were isolated from neonatal rat ventricles, and cultures of either myocytes alone or of myocytes in co-culture with fibroblasts were established and observed for 21 days. The beating rate in control myocytes increased rapidly, reached peak values on day 5 (266.2 +/- 58.2 beat/min), and then decreased by day 21. The beating rate of myocytes which were co-cultured with fibroblasts in group 2-1 (2-1 ratio of myocytes to fibroblasts, 6.0 x 10(5) total cells/well) was significantly lower than that in control myocytes, and showed a decreased peak value on day 7 (135.1 +/- 46.4). The beating rate in group 1-1 was significantly less than that of group 2-1, with a peak value on day 7 (85.9 +/- 24.9). Group 1-2 myocytes did not show a beating rate increase. Myocyte hypertrophy was measured after three days of culture. The surface area of myocytes which had been co-cultured with fibroblasts was significantly increased, as compared to that of control myocytes. In addition, myocyte surface area increased with increasing numbers of fibroblasts (mean myocyte surface areas in group 2-1, 1-1 and 1-2 were 143 +/- 21, 163 +/- 33, 206 +/- 38% of control, respectively). In conclusion, suppression of the myocyte beating rate and acceleration of myocyte hypertrophy are characteristic expressions of myocyte differentiation and growth during the neonatal period The present results suggest that fibroblasts play an important role in controlling myocyte development.