Effect of catecholamine-induced cardiac hypertrophy on the force–interval relationship

Cardiac hypertrophy was induced in adult female Wistar rats following 12 days of daily subcutaneous injections of isoproterenol (ISO). The left atria responded with a 13–14% increase in tissue growth, while the ventricles achieved a 34–39% increased tissue mass. Maximum force generation and twitch characteristics in 1.0 mM external Ca2+ for the left atria or the right papillary muscle were unchanged in the ISO-treated animals. The force–interval relation was determined at 26 °C between 0.5 and 120 s. The development of maximum force clearly passed through two phases identified as alpha and beta. To characterize these two processes the data were fitted to a two-term linear combination of exponentials (two-compartment model). The time constant and capacity of each process to contribute to the whole force–interval curve was determined by a four-parameter least square fit method. In control atrial muscle the time constants for the alpha and beta processes were 0.47 and 11.23 s, respectively. The contribution of each process to the total force curve in control atrial muscle was approximately 50% alpha and 50% beta. Following ISO-induced growth the time constants were 0.38 and 13.33 s with a shift of contributions towards 60% alpha and 40% beta. Control papillary muscle from the right ventricle had a similar alpha time constant of 0.49 s compared with atrial muscle but possessed a considerably slower beta time constant of 26.17 s. The contribution of each process to interval-dependent force development was 44.5 and 55.5%, respectively. Treatment with ISO to induce ventricular growth resulted in a 20% reduced alpha time constant, with a 45% increased contribution by the alpha process. These results suggest that during the development of catecholamine-induced hypertrophy, there is a significant change in the fundamental alpha process which appears to be mediated by a reduced time constant and an enhanced capacity to contribute to force development.