Experimental and Clinical Study on Desynchronization of Biological Rhythms in Heart Failure

点击翻译按钮获取中文摘要

Purpose :To elucidate the desynchronization of internal biological rhythms in heart failure, we predicted the optimal cardiac and respiratory rhythms for 1)contractility modulation and 2)sympathetic modulation, and examined ultradian dynamics of physical activity, hemodynamics, and autonomic function in 3)patients with heart failure and 4)free-moving conscious rats with heart failure.Methods & Results :1)Slowing heart rate seems to be beneficial for synchronization of cardiac rhythm with slow Ca2+ cycling in the failing heart. Using system identification technique, we developed a mathematical model of force-frequency response and mechanical restitution in human failing hearts and predicted the optimal heart rate for both Ca2+ cycling and cardiac pumping ability.2)Using system identification technique, we developed a model of respiratory modulation of sympathetic nerve activity and examined the optimal respiratory rhythm for effective sympathetic suppression in patients with heart failu … More re. The model predicted that a reduction of respiratory rhythm by half with doubling tidal volume suppressed sympathetic nerve activity three times greater than control, suggesting that a slowing respiration rhythm could effectively stabilize sympathetic tone in patients with heart failure.3)Power spectral analysis for all-day heart rate and physical activity revealed that a prominent ultradian rhythm existed in both heart rate and physical activity in patients with heart failure. A more prominent ultradian rhythm of circadian changes in heart rate and physical activity was found in 50% of the subjects with mild hart failure. Their ultradian power normalized by the total power averaged 36.3±5.4% in heart rate and 38.9±11.5% in physical activity. However, the incidence and magnitude of the ultradian power of physical activity declined as the heart failure progressed.4)Synchronization of ultradian rhythms of all-day physical activity, heart rate and blood pressure, autonomic function was examined in free-moving conscious rats with heart failure. A beautiful ultradian rhythm of activity was found in synchrony with hemodynamics and autonomic function but markedly attenuated in amplitude in the rat with heart failure.Conclusions :All these studies suggest that desynchronization of biological rhythms(activity, hemodynamics, and autonimic function) is a characteristic feature of heart failure and that slowing the biological rhythms could be effective for their resynchronization processes. Less