Myocyte growth without physiological impairment in gradually induced rat cardiac hypertrophy.
A surgical technique was developed to place sutures around the pulmonary arteries of young rats (about 1 month old and 100 g body weight). As the operated rats grew, the pulmonary arteries were gradually constricted, leading after 4-6 weeks to the development of severe right ventricular hypertrophy with free wall weights about twice those from control rats. There were no signs of heart failure or cardiac decompensation. Collagen concentrations were the same in operated and control rats. Myocytes were isolated from right ventricles by enzymatic digestion. Autoradiographic studies showed considerable uptake in non-myocyte nuclei. Myocyte sarcomere lengths were unchanged. However, myocyte lengths and areas increased sufficiently to account for the increase in free wall weights observed. Physiological studies were done on isolated papillary muscles and ventricular strands, which were subsequently fixed. The force-generating capability at optimum length, magnitude of active compliance, and maximum speed of shortening (using four different techniques) were measured in each isolated muscle. There were no significant changes observed between operated and control rats. Microscopic examination of the muscle cross-sections confirmed that average myocyte area in the muscles obtained from operated rats was significantly increased. The results show that it is possible to obtain considerable increases in average myocyte size (by about a factor of 2) while still maintaining normal physiological function.