John B. West

Continuous Distributions of Ventilation-Perfusion Ratios in Normal Subjects Breathing Air and 100% O2

A B S T R A C T A new method has been developed for measuring virtually continuous distributions of ventilation-perfusion ratios (VA/Q) based on the steadystate elimination of six gases of different solubilities. The method is applied here to 12 normal subjects, aged 21-60. In nine, the distributions were compared breathing air and 100% oxygen, while in the remaining three, effects of changes in posture were examined. In four young semirecumbent subjects (ages 21-24) the distributions of blood flow and ventilation with respect to VA/Q were virtually log-normal with little dispersion (mean log standard deviations 0.43 and 0.35, respectively). The 95.5% range of both blood flow and ventilation was from VA/Q ratios of 0.3-2.1, and there was no intrapulmonary shunt (VA/Q of 0). On breathing oxygen, a shunt developed in three of these subjects, the mean value being 0.5% of the cardiac output. The five older subjects (ages 39-60) had broader distributions (mean log standard deviations, 0.76 and 0.44) containing areas with VA/Q ratios in the range 0.01-0.1 in three subjects. As for the young subjects, there was no shunt breathing air, but all five developed a shunt breathing oxygen (mean value 3.2%,) and in one the value was 10.7%. Postural changes were generally those expected from the known effects of gravity, with more ventilation to high VA/Q areas when the subjects were erect than supine. Measurements of the shunt while breathing oxygen, the Bohr CO2 dead space, and the alveolar-arterial oxygen difference were all consistent with the observed distributions. Since the method involves only a short infusion of dissolved inert gases, sampling of arterial blood and expired gas, and measurement of cardiac output and minute ventiThis work was presented in part at the national meeting of the Federation of American Societies for Experimental

Ventilation-perfusion inequality in chronic obstructive pulmonary disease.

A multiple inert gas elimination method was used to study the mechanism of impaired gas exchange in 23 patients with advanced chronic obstructive pulmonary disease (COPD). Three patterns of ventilation-perfusion (Va/Q) inequality were found: (a) A pattern with considerable regions of high (greater than 3) VA/Q, none of low (less than 0.1) VA/Q, and essentially no shunt. Almost all patients with type A COPD showed this pattern, and it was also seen in some patients with type B. (b) A pattern with large amounts of low but almost none of high VA/Q, and essentially no shunt. This pattern was found in 4 of 12 type B patients and 1 of type A. (c) A pattern with both low and high VA/Q areas was found in the remaining 6 patients. Distributions with high VA/Q areas occurred mostly in patients with greatly increased compliance and may represent loss of blood-glow due to alveolar wall destruction. Similarly, well-defined modes of low VA/Q areas were seen mostly in patients with severe cough and sputum and may be due to reduced ventilation secondary to mechanical airways obstruction or distortion. There was little change in the VA/Q distributions on exercise or on breathing 100% O2. The observed patterns of VA/Q inequality and shunt accounted for all of the hypoxemia at rest and during exercise. There was therefore no evidence for hypoxemia caused by diffusion impairment. Patients with similar arterial blood gases often had dissimilar VA/Q patterns. As a consequence the pattern of VA/Q inequality could not necessarily be inferred from the arterial PO2 and PCO2.

Preferential expression of the maternally derived X chromosome in the mouse yolk sac.

Abstract We have studied the expression of the maternally derived X chromosome (X m ) and the paternally derived X chromosome (X p ) in female mouse conceptuses on the fourteenth day of gestation. We used an X-linked electrophoretic variant for phosphoglycerate kinase (PGK-1) to estimate the relative proportions of the expression of X m and X p in the fetus and in the yolk sac. Our results support the cytological observations of Takagi and Sasaki (1976) and suggest that X m is preferentially expressed in the mouse yolk sac. Further analysis strongly suggests that the paternally derived Pgk-1 allele (and therefore probably the whole of X p ) is not expressed in the mouse yolk sac endoderm. We have demonstrated that this effect is not caused by a selection pressure exerted by the phenotype of the maternal reproductive tract against cells which express X p . We therefore, conclude that the parental origin of X m and X p marks them as different from one another. Possible causes for the failure of the expression of X p in the yolk sac endoderm and the tissue specificity of the effect are discussed.

Ventilation-perfusion inequality and overall gas exchange in computer models of the lung

Abstract The effects of increasing ventilation-perfusion inequality on overall gas exchange were studied in digital computer models of the lung. Ventilation/unit volume and perfusion/unit volume were distributed log normally with respect to lung volume. Ventilation-perfusion inequality was found to affect the transfer of carbon dioxide nearly as much as oxygen. The reasons for the misconception that inequality does not interfere with carbon dioxide transfer are discussed. The effects of changing overall ventilation, blood flow, inspired oxygen, hemoglobin concentration, and the acid-base status of the blood were investigated when oxygen uptake and carbon dioxide output were held constant at normal values. In general, mismatch of ventilation and blood flow in a lung caused the arterial oxygen tension to fall and the carbon dioxide to rise; increasing overall ventilation rapidly restored blood carbon dioxide tensions to normal but improved oxygen tensions little. Considerable improvement in oxygen tensions occurred, however, if the oxygen dissociation curve was made linear. In spite of large increases in inspired oxygen, severe hypoxemia and large alveolar-arterial oxygen differences remained when the inequality was severe. The results help to explain how the lung maintains oxygen and carbon dioxide transfer in the face of ventilation-perfusion ratio inequality and may be useful in characterizing the degree of ventilation-perfusion inequality in real situations.

Effect of lung volume on the distribution of pulmonary blood flow in man.

Abstract The distribution of pulmonary blood flow was measured over a wide range of lung volumes in nine normal subjects in the seated erect position using radioactive xenon and a lung scanning technique. At functional residual capacity (FRC) blood flow decreased with distance down the lower third of the lung. This area of reduced basal blood flow was much less at higher lung volumes, but at volumes below FRC further reduction of blood flow in the dependent zone was seen. The reduction of pulmonary blood flow in a zone where vascular pressures because of gravity are highest is thought to be due to an increase in interstitial pressure affecting the vessels outside the influence of alveolar pressure. At normal lung volumes interstitial pressure is higher in the dependent zones of the lung in man mainly because of the reduced expansion of the lung parenchyma in these regions.

Stress failure of pulmonary capillaries: role in lung and heart disease

Pulmonary capillaries have extremely thin walls to allow rapid exchange of respiratory gases across them. Recently it has been shown that the wall stresses become very large when the capillary pressure is raised, and in anaesthetised rabbits, ultrastructural damage to the walls is seen at pressures of 40 mm Hg and above. The changes include breaks in the capillary endothelial layer, alveolar epithelial layer, and sometimes all layers of the wall. The strength of the thin part of the capillary wall can be attributed to the type IV collagen in the extracellular matrix. Stress failure of pulmonary capillaries results in a high-permeability form of oedema, or even frank haemorrhage, and is apparently the mechanism of neurogenic pulmonary oedema and high-altitude pulmonary oedema. It also explains the exercise-induced pulmonary haemorrhage that occurs in all racehorses. Several features of mitral stenosis are consistent with stress failure. Overinflation of the lung also leads to stress failure, a common cause of increased capillary permeability in the intensive care environment. Stress failure also occurs if the type IV collagen of the capillary wall is weakened by autoantibodies as in Goodpastures syndrome. Neutrophil elastase degrades type IV collagen and this may be the starting point of the breakdown of alveolar walls that is characteristic of emphysema. Stress failure of pulmonary capillaries is a hitherto overlooked and potentially important factor in lung and heart disease.

Increased Pulmonary Vascular Resistance in the Dependent Zone of the Isolated Dog Lung Caused by Perivascular Edema

Measurements of the distribution of blood flow in an isolated dog lung made with radioactive xenon showed a great increase in vascular resistance in the dependent zone of the lung in the presence of a raised pulmonary venous pressure in some preparations. Evidence that this increased vascular resistance was caused by perivascular edema consisted of the general correlation with interstitial edema, the regional distribution of the effect, the sensitivity to the arteriovenous pressure difference, the effect of certain infusions particularly hypertonic urea, and the demonstration of edema around the small arteries and veins in rapidly frozen sections. The mechanism of the increased resistance is postulated as an interference with the tethering effect of the lung parenchyma which normally holds the vessels open. The possible role of this mechanism in the increased pulmonary vascular resistance of patients with pulmonary venous hypertension is discussed.

DISTRIBUTION OF MECHANICAL STRESS IN THE LUNG, A POSSIBLE FACTOR IN LOCALISATION OF PULMONARY DISEASE

Abstract Experimental and theoretical studies show that the mechanical stresses in the upright lung are not uniform, but are much higher in the upper than lower zones. The stresses are greatest at the apex, where they may be several times larger than at the base of the lung. These high apical stresses are associated with larger alveoli and more negative intrapleural pressures than elsewhere in the lung. The uneven distribution of stress results from distortion of the lung by its own weight. The distribution of some forms of lung disease is closely related to this distribution of stress. Centrilobular emphysema develops first at the top of the lung and spreads downwards. It is suggested that this disease is caused by generalised bronchiolitis, with consequent mechanical failure and dilatation in the regions of highest stress. Spontaneous pneumothorax is commonly caused by the rupture of an apical bleb, because that is where the lung is stressed most. The development of apical bullae, and the cavities in pulmonary tuberculosis, are also related to this hitherto unrecognised factor.

Vulnerability of Pulmonary Capillaries in Heart Disease

The pulmonary blood-gas barrier presents a dilemma. It must be extremely thin for efficient gas exchange. However, it also needs to be immensely strong because the stresses in the pulmonary capillary wall become extremely high when the capillary pressure rises. Stress failure of the capillaries occurs in several pathological conditions. It causes high-permeability edema as in neurogenic pulmonary edema or high-altitude pulmonary edema; alveolar hemorrhage, which occurs in all galloping racehorses; or a combination of the two as in severe congestive heart failure. The vulnerability of the capillary wall to increased mechanical stress has not previously been sufficiently appreciated.

Regional Differences in the Lung

Marked differences of ventilation, blood flow, gas exchange, alveolar size, intrapleural pressures and mechanical stresses exist within the human lung and some of these are of special interest to the anesthesiologist in the context of anesthesia and postoperative care.