Cardiac output and mixed venous oxygen content measurements by a tracer bolus method: theory.

We present a bolus method of inert-gas delivery to the lungs that facilitates application of multiple inert gases and the multiple inert-gas-exchange technique (MIGET) model to noninvasive measurements of cardiac output (CO) and central mixed venous oxygen content Reduction in recirculation error is made possible by 1) replacement of sinusoidal input functions with impulse inputs and 2) replacement of steady-state analyses with transient analyses. Recirculation error reduction increases the inert-gas selection to include common gases without unusually high (and difficult to find) tissue-to-blood partition coefficients for maximizing the systemic filtering efficiency. This paper also presents a practical method for determining the recirculation contributions to inert expired profiles in animals and determining their specific contributions to errors in the calculations of CO and from simulations applied to published ventilation-perfusion ratio (V/Q) profiles. Recirculation errors from common gases were found to be reducible to the order of 5% or less for both CO and whereas simulation studies indicate that measurement bias contributions from recirculation, V/Q mismatch, and the V/Q extraction process can be limited to 15% for subjects with severe V/Q mismatch and high inspired oxygen fraction levels. These studies demonstrate a decreasing influence of V/Q mismatch on parameter extraction bias as the number of inert gases are increased. However, the influence of measurement uncertainty on parameter extraction error limits improvement to six gases.

Gas-blood Pco2 and Po2 equilibration in a steady-state rebreathing dog preparation.

Alveolar gas and mixed venous blood PCO2 and PO2 were compared in a steady-state rebreathing dog preparation, during spontaneous breathing and mechanical ventilation, by a new null-balancing method that removes potential biases in the comparison of measurements in the blood and gas phases and includes an inert gas test to verify the equilibration between the rebreathing lung and the bag. No systematic PCO2 and PO2 differences were observed under equilibrium conditions. However, inert gas studies suggested that a high percentage of measurements obtained during spontaneous breathing were unreliable because of inadequate equilibration between blood and rebreathing bag (attributable to reduced ventilation or perfusion) and that all mechanical ventilation measurements were acceptable. The present data support the view that no PCO2 or PO2 gradients exist when the pulmonary capillary blood and alveolar gas are in equilibrium; the data also suggest that the steady-state rebreathing dog preparation may not be completely stable and that the time course of PCO2 and PO2 in the rebreathing bag may not be reliable as a means of assessing the equilibration between blood and bag.

Pulmonary resistance and dynamic compliance as functions of respiratory frequency.

The behavior of pulmonary resistance (RL) and that of dynamic compliance (Cdyn) as functions of respiratory frequency (f) were compared in normal subjects and in patients with chronic obstructive pulmonary disease (COPD). Although both RL and Cdyn varied with f in most COPD patients and in some normal subjects, Cdyn appeared to be more sensitive than RL to variations of frequency; no significant changes in RL could be demonstrated in subjects in whom Cdyn was frequency dependent. The degree of frequency dependence of Cdyn was correlated with the severity of respiratory impairment (as quantified by conventional pulmonary function tests); in contrast, RL was not detectably frequency dependent in some subjects with advanced COPD. Compared with Cdyn, RL was more commonly nonlinearly related to respiratory frequency, often increasing at high breathing rates. Our results indicate that changes in RL with frequency are less predictable and more difficult to detect than the corresponding changes in Cdyn.

Hypocapnia and measurement of airflow resistance and dynamic compliance as functions of respiratory frequency.

Measurements of lung mechanical behaviour as a function of respiratory frequency may be associated with significantly increased ventilation at high breathing rates. It follows that these measurements may be influenced by hypocapnia which has been shown to increase airflow resistance and to decrease dynamic compliance. To examine this possibility we continuously monitored the end-tidal CO2 tension during the determination of pulmonary resistance and dynamic compliance as functions of frequency and we compared measurements obtained by the standard method and by a technique designed to prevent the development of hypocapnia at high breathing rates. We studied 11 patients with chronic obstructive pulmonary disease and also two smokers with normal spirometry and resistance. Although conventional measurements at frequencies higher than 40-45 breaths/min were associated with a significant decrease in end-tidal CO2, no systematic differences were found between the values of pulmonary resistance and dynamic compliance obtained by the two techniques. Our data indicate that the development of hypocapnia at high breathing rates does not significantly affect measurements of resistance and compliance as functions of frequency, at least when the duration of each period of hyperventilation is limited to the minimum necessary for a single determination, which was less than 30 seconds in the present study. A comparison of our results with previously published data suggests that the time factor may be critical with respect to the possible effects of hypocapnia on these measurements.

Exercise and distribution of inspired gas in patients with obstructive pulmonary disease.

The effects of moderate exercise on the distribution of inspired gas and efficiency of ventilation were studied by the multibreath nitrogen washout method in three subjects with asymptomatic asthma and 11 patients with chronic obstructive pulmonary disease (COPD). The nitrogen washout curves were analyzed according to a lung model consisting of a poorly ventilated compartment (slow space) and one or more better ventilated compartments (intermediate and fast compartments). The overall efficiency of ventilation was also estimated by the lung clearance index (LCI). An increase in the ventilation of both well ventilated and poorly ventilated lung compartments was generally observed during exercise; however, the magnitude of the change in the ventilation of the slow compartment in response to exercise varied from subject to subject; the change was related to the degree of functional impairment, as expressed by current pulmonary function tests (spirometry, airway resistance, and arterial blood gas measurements). The magnitude of the change in the ventilation of the better ventilated lung compartments did not vary significantly with the degree of functional impairment. LCI showed no uniform changes with exercise. Our results indicate that in patients with obstructive lung disease the effect of exercise on the distribution of inspired gas tends to vary with the severity of the disease. The nitrogen washout data also suggest that in these patients the pattern of gas distribution during exercise is not compatible with a high level of ventilatory efficiency.

Bronchodilator effects of nebulized fenoterol: a comparison with isoproterenol.

In an attempt to find the optimal single therapeutic dose of fenoterol inhalant solution administered by compressor-powered nebulization, bronchodilator and side effects of five different doses of fenoterol (0.5, 1.0, 1.5, 2.0, and 2.5 mg) and of placebo were compared with those of the recommended therapeutic dose delivered from a metered dose canister in 16 patients with reversible airway obstruction. The fenoterol (except for the metered dose) and the placebo were given in a double-blind, cross-over manner. In comparison with placebo, all doses of fenoterol produced a significant increase in average values of FEV1, FEF25-75%, FVC, and SGaw and decrease in FRC for five to eight hours. There was a trend for the bronchodilator action to become greater and more prolonged with increasing doses of fenoterol. Compared with 0.4 mg given from a metered dose canister, 0.5 mg of fenoterol delivered by compressor powered nebulization was equally effective in bronchodilator potency. Dose-by-dose comparison with isoproterenol indicates that fenoterol is a more potent and longer lasting bronchodilator and has no significant effect on heart rate and blood pressures. The most common side effects were shakiness or tremor of hands which appeared to be dose-related in terms of incidence and intensity. The results of the present study suggest that 0.5 to 1.0 mg of fenoterol is a suitable single therapeutic dose when administered by compressor-powered nebulization.

Measurement of oxygen consumption and carbon dioxide production rates by a tracer-bolus method.

A new method for measuring oxygen consumption and carbon dioxide production is described. The method is based on the injection of a helium bolus into the inspired gas for repeated breaths; the helium can be delivered through the mouth or through a nostril (the injection system being controlled by the integrated flow signal or by the signal of a thermistor, respectively). Compared with the conventional gas-collection technique, the tracer-bolus method allows more rapid and frequent measurements. The method does not necessarily require an airtight respiratory circuit, so that it can be conveniently applied in less cooperative subjects, including children. The results of validation studies based on a comparison with the standard gas-collection technique are presented; these results indicate that the measurements by the tracer-bolus method are accurate in normal subjects. In patients with obstructive lung disease, the determinations are associated with a systematic error, which is expected, the tracer-bolus method being based on a single-compartment, uniformly ventilated and perfused lung model; the error is, however, predictable from the degree of functional impairment and can be corrected using equations based on routine pulmonary function tests.

Regional lung expansion and vertical pleural pressure gradients in normal human subjects.

Using 133Xe and a single slow inspiration from near residual volume (RV) to total lung capacity (TLC), we measured regional lung volume continuously in six regions as a fraction of volume at maximal inflation in 57 normal non-smoking subjects (age: 20 to 82 years). We found that regional initial (i.e., near RV) volume/TLC increased significantly with aging in all regions for females whereas the increase in males was significant only in the upper regions. These results suggest that the aging process in the lung is accelerated in females. Some variability in regional volume measurements occurred when inspiration started from FRC rather than near RV. Although the patterns of regional expansion generally confirm those previously reported, it was found that the volume of vertically adjacent regions do frequently become equal and cross-over one another. Using the measurements of static compliance, regional V/TLC at FRC, and a passive model based upon an isotropic distribtion of intrinsic elasticity throughout the lung, the mean vertical pleural pressure gradient between upper and middle regions and middle and lower regions were estimated as 0.246 cmH2O/cm and 0.267 cmH2O/cm respectively. We believe that the regional expansion patterns which we observed can be explained by the interaction between a variable thoraco-diaphragm/abdominal motion and a passive elastic lung.

Flow and age dependence of airway closure and dynamic compliance.

The influence of expiratory flow rate and age on the results of measurement of closing volume (CV) of the lung have been studied by a nitrogen single-breath method in 66 asymptomatic lifetime nonsmoking normal subjects between 20 and 82 yr of age. Normal was defined as having values for spirometric measurements within a 95% tolerance interval of reported predicted normal mean values. For the CV determination, inspiratory flow rate was held constant at 0.51/s and studies were carried out at expiratory flow rates of 0.25, 0.5, 1.0, and 1.5 1/s. Our results show that CV expressed as a percentage of vital capacity (VC) and the slope of the alveolar plateau increases with increasing flow rate and age. Dynamic compliance (Cdyn) at frequencies corresponding to peak flow rates of 0.5 and 1.5 1/s was also measured and correlated well with the CV results. Frequency dependence of compliance with aging was demonstrated. Nine smokers with normal spirometric measurements and abnormal CV %VC were also studied. Since the results of Cdyn measurement differentiated only two-thirds of the smokers from the normal population, we suggest that the CV method is probably more sensitive than the Cdyn method for the detection of small airway obstruction.