FORCE-FREQUENCY RELATIONS DURING HEART-FAILURE IN PIGS

In isolated cardiac muscle from patients with severe heart failure (HF) the force-frequency relation (FFR) is often negative, but the characteristics of the FFR under basal conditions and its responsiveness to adrenergic stimulation have not been studied in the intact, failing heart. Severe HF was produced in pigs (n = 6) by continuous rapid left ventricular (LV) pacing (225 beats/min). In the conscious resting state, high-fidelity LV pressure and its maximum first derivative (LV dP/dt(max)) were obtained over a range of atrial pacing rates (100-225 beats/min) before (control) and after HF. Before HF, the relationship between increased heart rate and LV dP/df(max) (a measure of the FFR) was flat, but during dobutamine infusion the FFR showed a significant positive slope (P < 0.003). After HF, the basal FFR was depressed, but the slope of the FFR was not increased by dobutamine. After HF, responses of dP/dt(max) to slowing of HR by a specific sinus node inhibitor confirmed the absence of a negative basal FFR. In conclusion, the basal LV FFR in conscious pigs with severe HF was not negative. Unlike the normal heart, in HF beta-adrenergic receptor stimulation did not amplify the FFR, a phenomenon that could play an important role in the impaired response to exercise in patients with HF.