Periodic Breathing in Heart Failure Explained by Dynamic and Static Properties of Respiratory Control

Abstract

Objective The respiratory operating point is determined by the interplay between the controller and plant subsystem elements within the respiratory chemoreflex feedback system. This study aimed to establish the methodological basis for quantitative analysis of the open-loop dynamic properties of the human respiratory control system and to apply the results to explore detailed mechanisms of the regulation of respiration and the possible mechanism of periodic breathing in chronic heart failure. Methods and Results In healthy volunteers, we measured arterial CO2 partial pressure (PaCO2) and minute ventilation (V̇E) to estimate the dynamic properties of the controller (PaCO2→V̇E relation) and plant (V̇E→PaCO2 relation). The dynamic properties of the controller and plant approximated first- and second-order exponential models, respectively, and were described using parameters including gain, time constant, and lag time. We then used the open-loop transfer functions to simulate the closed-loop respiratory response to an exogenous disturbance, while manipulating the parameter values to deviate from normal values but within physiological ranges. By increasing both the product of gains of the two subsystem elements (total loop gain) and the lag time, the condition of system oscillation (onset of periodic breathing) was satisfied. Conclusion When abnormality occurs in a part of the respiratory chemoreflex system, instability of the control system is amplified and may result in the manifestation of respiratory abnormalities such as periodic breathing.