Gas exchange in chronic thromboembolism after pulmonary thromboendarterectomy.

Thromboendarterectomy is the treatment of choice for chronic large vessel thromboembolic pulmonary hypertension. To identify the mechanisms responsible for the improvement in gas exchange following thromboendarterectomy, we studied nine patients with chronic thromboembolic pulmonary hypertension before and eight to 18 months after surgery using the multiple inert gas elimination technique. Preoperatively, all subjects had pulmonary hypertension and were hypoxemic or had an elevated P(A-a)O2. The VA/Q distribution was widened with an elevated VD/VT and a low cardiac index. After thromboendarterectomy, significant improvement had occurred. The VA/Q distribution had narrowed to near normal, and the cardiac index increased. It was concluded that thromboendarterectomy improved gas exchange both by improving VA/Q relationships and by increasing cardiac output.

Information content of the multibreath nitrogen washout: effects of experimental error.

Methods that recover a continuous distribution of specific ventilation (ventilation-to-volume ratio, VA/V) from the multibreath N2 washout curve theoretically can resolve up to four modes of ventilation and reveal the major characteristics of the underlying distribution if experimental error is absent. This paper quantitatively assesses the effects of experimental error on resolution. The washout curves from five typical distributions were studied using linear programming and Monte Carlo methods. A measurement error of 0.1% was assumed in the mixed-expired N2 signal. Only 7 of the first 17 breaths contribute independent information about the underlying distribution, and only rough resolution of the underlying distribution is possible in the presence of error. Only two modes of ventilation plus an estimate of dead space can be confidently resolved. It is not possible to separate VA/V greater than 10 from dead space. A 10-fold reduction in experimental error will not greatly improve resolution. Experimental error, by reducing the linear independence of the defining kernels, significantly limits the information content and resolution of the multibreath N2 washout.

Linear programming analysis of VA/Q distributions: limits on central moments.

Linear programming examines the boundaries of infinite sets. We used this method with the multiple-inert gas-elimination technique to examine the central moments and arterial blood gases of the infinite family of ventilation perfusion (VA/Q) distributions that are compatible with a measured inert gas-retention set. A linear program was applied with Monte-Carlo error simulation to theoretical retention data, and 95% confidence intervals were constructed for the first three moments (mean, dispersion, and skew) and the arterial PO2 and PCO2 of all compatible blood flow distributions. Six typical cases were studied. Results demonstrate narrow confidence intervals for both the lower moments and predicted arterial blood gases of all test cases, which widen as moment number or error increase. We conclude that the blood gas composition and basic structure of all compatible VA/Q distributions are tightly constrained and that even subtle changes in this structure, as may occur experimentally, can be identified.

Linear programming analysis of VA/Q distributions: average distribution.

The defining equations of the multiple inert gas elimination technique are underdetermined, and an infinite number of VA/Q ratio distributions exists that fit the same inert gas data. Conventional least-squares analysis with enforced smoothing chooses a single member of this infinite family whose features are assumed to be representative of the family as a whole. To test this assumption, the average of all ventilation-perfusion ratio (VA/Q) distributions that are compatible with given data was calculated using a linear program. The average distribution so obtained was then compared with that recovered using enforced smoothing. Six typical sets of inert gas data were studied. In all sets but one, the distribution recovered with conventional enforced smoothing closely matched the structure of the average distribution. The single exception was associated with the broad log-normal VA/Q distribution, which is rarely observed using the technique. We conclude that the VA/Q distribution conventionally recovered approximates a simple average of all compatible distributions. It therefore displays average features and only that degree of fine structural detail that is typical of the family as a whole.

Information content of multiple inert gas elimination measurements.

The multiple inert gas elimination technique provides a fundamental assessment of the distribution of ventilation-perfusion (VA/Q) ratios in the lung. The resolution of the finer structure of this distribution is limited however. This study examines the theoretical basis of this limitation and presents an objective method for evaluating the independence of inert gas measurements. It demonstrates the linear dependence of the inert gas kernels and their filtering characteristics to be the factors most limiting information content. The limited number of gases available for measurement and experimental error are lesser limitations. At usual levels of experimental error, no more than seven different inert gases having partition coefficients between those of SF6 and acetone will provide independent information, and information content will be maximized by choosing gases with partition coefficients spaced equally on a logarithmic scale. A fivefold reduction in experimental error will not significantly alter the information content of the measurements. The analysis applies equally to other methods of multiple inert gas elimination data interpretation.

Pulmonary gas exchange in humans during normobaric hypoxic exercise.

Previous studies (J. Appl. Physiol. 58: 978-988 and 989-995, 1985) have shown both worsening ventilation-perfusion (VA/Q) relationships and the development of diffusion limitation during heavy exercise at sea level and during hypobaric hypoxia in a chamber [fractional inspired O2 concentration (FIO2) = 0.21, minimum barometric pressure (PB) = 429 Torr, inspired O2 partial pressure (PIO2) = 80 Torr]. We used the multiple inert gas elimination technique to compare gas exchange during exercise under normobaric hypoxia (FIO2 = 0.11, PB = 760 Torr, PIO2 = 80 Torr) with earlier hypobaric measurements. Mixed expired and arterial respiratory and inert gas tensions, cardiac output, heart rate (HR), minute ventilation, respiratory rate (RR), and blood temperature were recorded at rest and during steady-state exercise in 10 normal subjects in the following order: rest, air; rest, 11% O2; light exercise (75 W), 11% O2; intermediate exercise (150 W), 11% O2; heavy exercise (greater than 200 W), 11% O2; heavy exercise, 100% O2 and then air; and rest 20 minutes postexercise, air. VA/Q inequality increased significantly during hypoxic exercise [mean log standard deviation of perfusion (logSDQ) = 0.42 +/- 0.03 (rest) and 0.67 +/- 0.09 (at 2.3 l/min O2 consumption), P less than 0.01]. VA/Q inequality was improved by relief of hypoxia (logSDQ = 0.51 +/- 0.04 and 0.48 +/- 0.02 for 100% O2 and air breathing, respectively). Diffusion limitation for O2 was evident at all exercise levels while breathing 11% O2.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary gas exchange in humans during exercise at sea level.

Previous studies have shown both worsening ventilation-perfusion (VA/Q) relationships and the development of diffusion limitation during exercise at simulated altitude and suggested that similar changes could occur even at sea level. We used the multiple-inert gas-elimination technique to further study gas exchange during exercise in healthy subjects at sea level. Mixed expired and arterial respiratory and inert gas tensions, cardiac output, heart rate, minute ventilation, respiratory rate, and blood temperature were recorded at rest and during steady-state exercise in the following order: rest, minimal exercise (75 W), heavy exercise (300 W), heavy exercise breathing 100% O2, repeat rest, moderate exercise (225 W), and light exercise (150 W). Alveolar-to-arterial O2 tension difference increased linearly with O2 uptake (VO2) (6.1 Torr X min-1 X 1(-1) VO2). This could be fully explained by measured VA/Q inequality at mean VO2 less than 2.5 l X min-1. At higher VO2, the increase in alveolar-to-arterial O2 tension difference could not be explained by VA/Q inequality alone, suggesting the development of diffusion limitation. VA/Q inequality increased significantly during exercise (mean log SD of perfusion increased from 0.28 +/- 0.13 at rest to 0.58 +/- 0.30 at VO2 = 4.0 l X min-1, P less than 0.01). This increase was not reversed by 100% O2 breathing and appeared to persist at least transiently following exercise. These results confirm and extend the earlier suggestions (8, 21) of increasing VA/Q inequality and O2 diffusion limitation during heavy exercise at sea level in normal subjects and demonstrate that these changes are independent of the order of performance of exercise.

Computer simulation of mammalian gas-exchange.

Gas exchange efficiency is dependent upon the distribution of ventilation to perfusion throughout the lung, as well as the position and shape of the oxygen and carbon dioxide dissociation curves, and the composition of mixed venous blood. Computer simulation has allowed practical investigation of these relationships. A BASIC program suitable for small microcomputers is presented which calculates the arterial blood gases and gas transport corresponding to an arbitrary VA/Q distribution and mixed venous composition. The needed theory and equations are developed, the program is discussed, and an example is presented.

Mechanisms of hypoxemia in chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension is characterized by widespread central obstruction of the pulmonary arteries with organized thrombus and thereby differs substantially from other forms of pulmonary hypertension. We studied 25 patients using the multiple inert gas elimination technique to identify and quantitate the physiologic mechanisms of hypoxemia in this disorder. All patients had chronic obstruction of the central pulmonary arteries, which was demonstrated angiographically and later surgically confirmed. All patients but one were hypoxemic (PaO2 = 65 +/- 11 mm Hg, PaCO2 = 32 +/- 4 mm Hg, AaPO2 = 45 +/- 14 mm Hg), and all patients had pulmonary hypertension (mean Ppa = 45 +/- 11 mm Hg) with an elevated pulmonary vascular resistance (mean PVR = 1,000 +/- 791 dyne/s/cm5, normal less than 300). The cardiac index was reduced (1.7 +/- 0.6 L/min/m2), as was the P-vO2 (31 +/- 5 mm Hg). Inert gas studies revealed widened unimodal Va/Q distributions in 20 of 25 subjects, with a log standard deviation of 1.01 +/- 0.32 (upper limit of normal, 0.6; ages 20 to 40), shunt = 0.03 +/- 0.05 of cardiac output, and dead space of 3.4 +/- 1.1 ml/kg (upper limit of normal, 2.9). The VD/VT ratio was 0.51 +/- 0.10. No low (VA/Q less than 0.1) or high (VA/Q greater than 10.0) regions were present, and no evidence for diffusion limitation of O2 transfer at rest was found. The low cardiac output and resulting low P-VO2 were responsible for approximately 33% of the increased AaPO2. The magnitude of the VA/Q abnormality correlated poorly with the PVR, the mean Ppa, or the magnitude of vascular obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Patterns of pulmonary perfusion scans in normal subjects. IV. The prevalence of abnormal scans in smokers 30 to 49 years of age.

The usefulness of ventilation-perfusion scans in the diagnosis of pulmonary embolism is limited by the wide range of pulmonary diseases that are associated with abnormal scans, and by the largely undetermined prevalence of abnormal scans in persons without cardiopulmonary disease. In prior studies, we found perfusion defects to be rarely present in young persons and in older nonsmokers. To determine if normal older smokers have a higher prevalence of abnormal ventilation and perfusion scans, we performed six-view 99mTc perfusion (Q) scans and 133Xe ventilation (V) scans in 40 subjects 30 to 49 yr of age who had no known cardiopulmonary disease. Each subject had undergone a history, physical examination, electrocardiogram, spirometry, and posteroanterior chest roentgenogram prior to scanning. All V and Q scans were interpreted blindly and independently by two experienced readers. No subject demonstrated a lobar or segmental defect on two views. One subject had a matched subsegmental defect, and one subject had delayed washout from a subsegmental area of the right upper lobe during V scanning, with a normal Q scan. We conclude that abnormal V and Q scans are uncommon among normal smokers 30 to 49 yr of age.