Determinants of ventilatory instability and variability.

This paper reviews the major mechanisms that can give rise to various forms of variability in the ventilatory pattern. First, an elevated controller gain, coupled with the presence of delays and response lags in the chemoreflex loops, can lead to instability in feedback control and give rise to periodic breathing. This form of ventilatory stability can be assessed quantitatively by employing the concept of 'loop gain'. Several different methods of estimating loop gain from steady state or dynamic respiratory measurements are discussed. An inherently stable respiratory control system can also exhibit periodic behavior due to the influence of primary fluctuations in sleep-wake state and other physiological variables, such as cardiac output and cerebral blood flow. Self-sustained, irregular ventilatory fluctuations may be generated by nonlinear dynamic interactions between various components of the respiratory control system, such as the lung vagal afferents and the respiratory pattern generator, or through the propagation of stochastic disturbances around the chemoreflex loops.