Left ventricular pressure response to small-amplitude, sinusoidal volume changes in isolated rabbit heart

Abstract

The objective was to determine the dynamics of contractile processes from pressure responses to small-amplitude, sinusoidal volume changes in the left ventricle of the beating heart. Hearts were isolated from 14 anesthetized rabbits and paced at 1 beats/s. Volume was perturbed sinusoidally at four frequencies (f) (25, 50, 76.9, and 100 Hz) and five amplitudes (0.50, 0.75, 1.00, 1.25, and 1.50% of baseline volume). A prominent component of the pressure response occurred at the f of perturbation [infrequency response, delta Pf(t)]. A model, based on cross-bridge mechanisms and containing both pre- and postpower stroke states, was constructed to interpret delta Pf(t). Model predictions were that delta Pf(t) consisted of two parts: a part with an amplitude rising and falling in proportion to the pressure around that which delta Pf(t) occurred [Pr(t)], and a part with an amplitude rising and falling in proportion to the derivative of Pr(t) with time. Statistical analysis revealed that both parts were significant. Additional model predictions concerning response amplitude and phase were also confirmed statistically. The model was further validated by fitting simultaneously to all delta Pf(t) over the full range of f and delta V in a given heart. Residual errors from fitting were small (R2 = 0.978) and were not systematically distributed. Elaborations of the model to include noncontractile series elastance and distortion-dependent cross-bridge detachment did not improve the ability to represent the data. We concluded that the model could be used to identify cross-bridge rate constants in the whole heart from responses to 25- to 100-Hz sinusoidal volume perturbations.