Estimation of chemoreflex loop gain using pseudorandom binary CO2 stimulation.

We have developed a method for deriving estimates of the chemoreflex control loop gain (LG) from the ventilatory response to inhaled CO2, modulated between 0% and 5% in the form of a pseudorandom binary sequence. The corresponding changes in alveolar (and thus, arterial) CO2 result from two components: 1) the direct effect of breath-to-breath changes in inhaled CO2 and 2) the chemoreflex-mediated changes in ventilation. LG between 0.01 and 0.03 Hz, the frequency range pertinent to periodic breathing, was estimated by computationally delineating the first component from the overall ventilatory response. The method was tested against simulated and experimental data. In both cases, we found strong correlations between our predictions and LG magnitude estimates derived by other methods. However, LG phase estimates were considerably more variable when compared to model predictions based on small-signal analysis. We propose that our method, which uses data from a single test procedure lasting < 10 min, may be more useful than traditional tests of chemoresponsiveness for the quantitative assessment of respiratory control stability during changes in sleep-wake state.

Transduction dynamics of intrapulmonary CO2 receptors.

We have developed a functional model for quantitatively characterizing the transduction dynamics of the intrapulmonary CO2 receptors (IPC) in the snake lung. The model was based on experiments in which the neural discharges of several IPCs were recorded in response to abrupt step changes in CO2 concentration. Initial attempts to model the transduction dynamics linearly proved inadequate, although the linear model captured gross features such as rate sensitivity and the existence of two time constants in the adaptation time-course. However, with the incorporation of two static nonlinear features, namely, thresholding and preferential directionality of the rate-sensitive component, it was possible to account for over 80% of the total variation in the data. The model produced accurate predictions of IPC responses to other inputs, such as pseudorandom binary changes in CO2. The model also allows the prediction of IPC discharge in spontaneous breathing given measurements of lung CO2 concentration, and may serve as a starting point for further studies of transduction mechanisms at the cellular level.

Optimal ventilatory patterns in periodic breathing.

The goal of this study was to determine whether periodic breathing (PB), which is highly prevalent during sleep at high altitudes, imposes physiological penalties on the respiratory system in the absence of any accompanying disease. Using a computer model of respiratory gas exchange, we compared the effects of a variety of PB patterns on the chemical and mechanical costs of breathing to those resulting from regular tidal breathing. Although PB produced considerable fluctuation in arterial blood gas tensions, for the same cycle-averaged ventilation, higher arterial oxygen saturation and lower arterial carbon dioxide levels were achieved. This result can be explained by the fact that the combination of large breaths and apnea in PB leads to a substantial reduction in dead space ventilation. At the same time, the savings in mechanical cost achieved by the respiratory muscles during apnea partially offset the increase during the breathing phase. Consequently, the "pressure cost," a criterion based on mean inspiratory pressure, was elevated only slightly, although the average work rate of breathing increased significantly. We found that, at extreme altitudes, PB patterns with clusters of 2 to 4 large breaths that alternate with apnea produce the highest arterial oxygenation levels and lowest pressure costs. The common occurrence of PB patterns with closely similar features has been reported in sleeping healthy sojourners at extreme altitudes. Taken together, these findings suggest that PB favors a reduction in the oxygen demands of the respiratory muscles and therefore may not be as detrimental as it is generally believed to be.

Optimal application of high-frequency ventilation in infants: a theoretical study.

A recent multicenter study of preterm infants concluded that high-frequency ventilation (HFV) applied at 15 Hz, in comparison with conventional mechanical ventilation (CMV), did not lead to reduced incidence of barotrauma, contrary to previous expectations. The primary goal of the present theoretical study was to determine whether computed estimates of lung pressures during HFV and CMV are consistent with these findings. An existing theoretical model of lung mechanics and gas transport in HFV was modified for applicability to neonates. New features, such as expiratory flow limitation and pulmonary air leak, were also incorporated. Simulations with the model were conducted assuming combinations of frequency and tidal volume that maintained a constant level of eucapnia. We found that peak alveolar pressures and the magnitude of alveolar pressure swings resulting from HFV at 15 Hz were in general comparable to those produced by CMV in healthy neonates and infants with bronchopulmonary dysplasia; peak alveolar pressures in the latter group tended to be higher with HFV than in CMV. Application of HFV at 15 Hz was even less advantageous than CMV when pulmonary air leak was also present in the infants with bronchopulmonary dysplasia. However, the model predicted the existence of an optimal range of frequencies between 2 and 4 Hz in which alveolar pressure swings and peak alveolar pressures could be minimized, and in some cases, reduced below the levels produced by CMV.

Use of a random forcing for high-frequency ventilation.

Previous applications of high-frequency oscillatory ventilation (HFOV) have used cyclic forcings with the frequency of oscillation considered to be a fundamental parameter. A question that is addressed in the present study is whether or not periodicity is an essential requirement for this mode of ventilation to occur. It was found possible to adequately ventilate anesthetized and paralyzed cats with volume excursions below the dead-space level using a random band-limited forcing. Experimental conditions were close to a constant flow variance (VARF) state, and arterial CO2 tension varied linearly as a function of the ratio of noise bandwidth and VARF. Periodicity per se did not appear to be a requirement for HFOV to occur, a result consistent with predictions of Taylor dispersion theory.

Analysis of the gas exchange system dynamics during high-frequency ventilation.

High-frequency ventilation (HFV) as a form of artificial respiration has attracted interest in recent years as a means of reducing the risk of barotrauma in clinical applications. This paper explores the high-frequency dynamics of the gas exchange system in order to obtain mathematical models that allow optimization studies aimed at answering the question: What is the optimum ventilatory waveform that secures a certain level of gas exchange while minimizing the resulting fluctuations in pleural or alveolar pressure? Two classes of input are considered: sinusoids and band-limited white noise. A model for the dynamic relation between tracheal flow and CO2 tension is obtained from experimental data which, in combination with existing models relating tracheal flow to pleural or alveolar pressure, allows optimization of the input flow waveform for a given level of CO2 elimination rate. The developed relation between CO2 elimination rate and input was verified by experimentally measured arterial CO2 tension.