Diastolic heart disease (DHD) accounts for half of all heart diseases worldwide. Diastolic dysfunction (DDx), an impairment in relaxation, is common to all etiologies of HD with echocardiography being the primary clinical diagnostic used to grade DDx. However, diagnoses of DDx can go undetected when measured at rest which presents clinically as exercise intolerance, the inability to have sustained increases in heart rate. The heart utilizes increases in heart rate to increase cardiac output which subsequently leads to increases in stroke volume. This phenomenon is known as the force frequency response. While it is known that DHD patients have reduced modulation of cardiac output leading to less cardiac reserve, less is known of the microtubule contribution to the force frequency response. We have examined the role of the microtubular network on the force frequency response in a model of DHD. Using myocardial slices from ZSF1 lean and obese rats we measured cardiac work output, end diastolic elastance, relaxation kinetics, and relaxation velocity treated with colchicine or paclitaxel treatment and additionally varied pacing frequency. Increased pacing resulted in increased cardiac work output and reduced end diastolic elastance in both the lean and obese animals. Colchicine retained the benefits from accelerated pacing on cardiac output while paclitaxel reduced cardiac output and increased end diastolic stiffness.
Hancock et al. (Sun,) studied this question.