Compensatory changes in Ca²⁺ and myocardial O₂ consumption in β-tropomyosin transgenic hearts

Transgenic mice overexpressing β-tropomyosin have increased myofilament Ca²⁺ sensitivity that we hypothesized would result in altered relationships among pressure and heart rates, intracellular Ca²⁺, and myocardial O₂ consumption. In perfused hearts from transgenic mice there was a marked negative force-frequency response between 6 and 10 Hz with a 30 ± 3% reduction in peak-positive first derivative of pressure development over time (dP/dt) compared with 14 ± 2% in wild-type mice (P < 0.001). At 8 Hz systolic pressures were normal, though peak systolic intracellular Ca²⁺ was significantly reduced in transgenic mice versus wild type (726 ± 61 vs. 936 ± 67 nM, P < 0.05) indicating an alteration in the pressure-Ca²⁺ relationship. Over a wide range of positive and negative inotropic interventions there were normal developed pressures, though marked elevations in myocardial O₂ consumption (15-54%). Because pressures are normal and intracellular Ca²⁺ decreased and myocardial O₂ consumption increased, this suggests that these abnormalities are at least in part compensatory mechanisms to the altered myofilament function.