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Although there is present agreement that intrapleural pressure is not uniform throughout the thoracic cavity there is disagreement both as to the magnitude of this difference and as to its significance. A new method has been employed (flow through a Starling resistor) for measuring pleural and esophageal pressure. There appears to be an area in the cephalad thorax, both in the horizontal and vertical head up position, in which end expiratory esophageal and pleural pressure are more negative than in the remainder of the thoracic cavity. The method employed and the possible significance of the findings are discussed.

The frequency function of transit times through the pulmonary vascular system in dogs was obtained by deconvolution of a pair of simultaneous tracer dilution curves. One tracer dilution curve represented transit times from pulmonary artery to aorta; the other represented transit times from left atrium to aorta. Theory of and requirements for deconvolution are presented. Two preparations were used: closed chest with recirculation, open chest with only myocardial recirculation. The frequency function of pulmonary vascular transit times was skewed markedly to the right. At constant cardiac output and left atrial pressure it was unaffected by change in heart rate or by respiratory movements. Frequency functions of transit time obtained by deconvolution of observed tracer concentration curves, including recirculation, were compared with those obtained by monoexponential extrapolation of the same tracer concentration curves to "eliminate" recirculation. If recirculation seemed to appear before the observed concentration curve (aortic sampling following pulmonary arterial injection) fell to 20% of peak, monoexponential extrapolation led to a 10% overestimate of mean transit time and to greater errors in estimate of higher moments. If recirculation did not seem to occur until the concentration fell to 10% or less of peak, there was no difference between the frequency functions of transit times calculated by the two methods. Increased coefficients of variance and skewness were associated with large mean transit times produced by hypovolemia and reduced cardiac output secondary to withdrawal of blood.

In 17 anesthetized dogs, 50–150 ml of isotonic saline or human amniotic fluid were instilled into a degassed lobe and after 2–6 hr of spontaneous or artificial ventilation, the lungs were excised. Static pressure-volume and extract surface tension values were then determined on a fluid- and a nonfluid-instilled lobe from each animal. When compared with nonfluid-instilled lobes the fluid-instilled lobes were found to have proportionately smaller volumes at maximum inflation ( P < .02) and during deflation ( P < .001) as well as regional areas with higher surface tension properties ( P < .001). It is proposed that the pressure-volume studies may furnish a useful means of assessing the anatomical extent of alterations in lung surface tension. There was a significant negative correlation between maximum inflation volumes and maximum surface tensions ( P < .001) as well as between the volumes during deflation and the minimum surface tensions ( P < .001). It is concluded that intra-alveolar fluid may inactivate or displace the surface-active material from the alveolar lining membrane. amniotic fluid; lung pressure-volume studies; lung surfactant Submitted on April 11, 1963

Two methods for estimating pulmonary diffusing capacity (steady-state O2 method of Lilienthal and Riley and steady-state CO method of Filley) were compared by applying them simultaneously in three ...

Disinfection of air in lower part of a room by ultraviolet irradiation of upper air has been studied after artificial dissemination of test organisms (Serratia marcescens). On basis of disinfection rates in lower air with different intensities of UV in upper air, the rates at which organisms are killed in upper air and at which air mixes between upper and lower parts of the room were calculated. By performing studies under different conditions of air motion, it was possible to analyze factors affecting air mixing and upper-air disinfection. With no fans to increase air motion, a single 30-w UV tube increased the rate of disappearance of organisms from lower part of room by the equivalent of 61 air changes per hour (median value). With a large-bladed ceiling fan, the same UV tube almost doubled the rate of disappearance of organisms.

We suggest that the acute asthmatic attack can be characterized as follows. The segmental and smaller bronchi become markedly constricted with a tendency toward complete closure. The constriction can be opposed by an increase in the static transpulmonary pressure which increases the distending pressure of the bronchi. The increase in distending pressure is brought about by the patient breathing nearer his total lung capacity. If he can breathe at a high enough level, the bronchi approach their original dimensions. Even so, during forced expirations these same airways have a tendency to collapse more readily than normal bronchi as the pressure within them falls relative to the pleural pressure with increasing flow. Breathing much nearer total lung capacity is perhaps the principal cause of the early circulatory and metabolic changes: increased oxygen consumption, increased cardiac output, and pulmonary hypertension. If breathing can occur at a sufficiently high lung volume, gas exchange is unaltered; but some areas tend to remain underventilated with resulting hypoxia.

Lung clearance has been studied, with external scanning, in 20 living rats after inhalation or intratracheal injection of viscose rayon fibers labeled with radioactive iodine (131I). The clearance rates after both methods of administration appear to occur in two phases. The initial rate of clearance for both modes of administration takes place with a half-life of about two to four hours. The second phase of clearance was much slower after aerosol inhalation than after intratracheal injection. The difference in clearance rates between the two modes of administration became significant 32 hours after exposure. The data suggest that, after aerosol inhalation, a significant amount of particles is deposited in peripheral lung areas, while approximately the same range of size fibers, if injected intratracheally, are deposited within the reach of the mucociliary transport mechanism.

The effect of transpulmonary pressure (Ptp) on gas exchange in the dog lung was studied in 10 open-chested dogs. Rates of pulmonary perfusion and ventilation were held constant (right heart bypass and pump respirator) while Ptp was varied. Alveolar dead space ventilation and alveolar shunt perfusion were calculated from CO2 and O2 gradients. The results are finally expressed in terms of a three-compartment lung model. It is shown that a misinterpretation is possible if alveolar dead space or alveolar shunt compartments are expressed as fractions, respectively, of all ventilated or all perfused alveoli, therefore each has been expressed as a fraction of the whole lung. It is concluded that the alveolar shunt compartment decreased as Ptp was increased, over the lower range of Ptp studied. No significant change was detected in the alveolar dead space compartment, as Ptp was varied. alveolar-arterial O2 gradient; anatomical dead space; arterial-alveolar CO2 gradient; distribution of pulmonary perfusion; distribution of pulmonary ventilation; right heart bypass preparation; ventilation/perfusion relationships Submitted on February 16, 1965

The effect of epinephrine on peripheral circulation was studied in ten anesthetized open-chest dogs. Blood flow and right atrial pressure were independently controlled by a right heart bypass; changes in blood volume could be precisely determined from the changes occurring in the bypass reservoir. At constant blood flow and right atrial pressure, a constant infusion of epinephrine (5.8 µg/kg min -1 ) decreased blood volume by an average of 208 ml. During epinephrine infusion, the ratio of changes in blood volume to changes in blood flow measured at constant right atrial pressure, (Δ V /Δ Q · ) Pra , decreased from 0.226 minutes to 0.153 minutes and the ratio of changes in blood volume to changes in right atrial pressure at constant blood flow, the vascular compliance, decreased from 27.1 ml/cm H 2 O to 20.7 ml/cm H 2 O. Transient changes in blood volume following a step decrease in right atrial pressure at constant blood flow showed that blood was draining from two vascular compartments with different time constants: 0.059 minutes and 0.388 minutes before epinephrine infusion and 0.058 minutes and 0.486 minutes during epinephrine infusion. We analyzed the data using a mathematical model of the peripheral circulation consisting of two compartments with different time constants. The analysis showed that the primary effect of epinephrine on the systemic circulation was to redistribute blood flow away from the compartment with the longest time constant. The reduction in (ΔV/Δ Q · ) pra and the decrease in blood volume at constant flow and right atrial pressure were essentially determined by the change in flow distribution brought about by a change in arteriolar tone and not by a change in venous tone.

The static pressure-volume characteristics of the lungs were determined in 28 normal males between the ages of 21 and 76 years. Transpulmonary pressures were measured in relation to absolute lung volumes throughout the entire range of the vital capacity, both on inspiration and expiration. There was an increase in residual volume and a decrease in vital capacity, but no change in the slope or position of the pressure-volume curve with advancing age. It appeared that the older subjects were unable to change transpulmonary pressure between residual volume and total lung capacity to the same extent as the younger subjects. The results suggest that with advancing age there is little change in the intrinsic static pressure-volume characteristics of the lungs themselves, and that all of the significant changes with age are more likely due to changes in either the compliance or muscle power of the thorax. Submitted on December 24, 1959

Physiologic dead space was determined in the supine and upright postures by simultaneous sampling and subsequent analysis of arterial blood and expired gas for Pco2. In seven normal men there was invariably a higher dead space in the upright than in the supine position. The difference averaged 83 ml and was statistically significant (S.E. 25 ml and P < 0.01). The ratio of dead space to tidal volume also invariably increased on assuming the upright posture. Evidence is presented for believing that most of the change in physiologic dead space resulted from a change in alveolar dead space. Estimated changes in the ratio of alveolar dead space to alveolar tidal volume suggest that approximately one seventh of the total number of alveoli became nonperfused on changing from the supine to the erect posture. These findings are consistent with bronchospirometric and hemodynamic evidence that the apex of the lung is virtually nonperfused in the resting human subject in the upright posture. Submitted on November 12, 1958

Submitted 16 October 1964 A method was developed that permitted changes in the pressure-volume characteristics of large intrapulmonary vessels occurring with changes in the composition of alveolar gas to be studied in excised lungs. The capillary bed was emptied by keeping intravascular pressure well below alveolar pressure, and the relationship between changes in the volume of the pulmonary arteries or veins with changes in transpulmonary pressure was measured. The volume of the arteries and veins always decreased with a decrease in transpulmonary pressure, but when the alveoli contained carbon dioxide, the decrease in vascular volume was less, for the same decrease in transpulmonary pressure, than when the alveoli contained oxygen or nitrogen without carbon dioxide. This change with carbon dioxide was probably due to a decrease in the compliance of the larger intrapulmonary arteries and veins. Since there was no pathway for carbon dioxide to enter these vessels except by diffusion from the alveoli, it is concluded that carbon dioxide can act directly on the intrapulmonary arteries and veins to reduce their compliance, but it is not known whether this effect has physiological significance. No effect on the large pulmonary vessels was found with variations in alveolar concentrations of oxygen. blood vesselsblood volumecarbon dioxidediffusionlungspulmonary circulation

The hypothesis that cyclic variation of CO2 tension of the arterial blood (PaCOCO2) about its mean produces an additional stimulus to ventilation was tested in the dog. Oscillations of alveolar carbon dioxide tension were produced by the intermittent administration of 20% CO2 for 1 breath every 7–12 breaths. The increment in ventilation per mm Hg rise in mean PaCOCO2 during the intermittent administration of 20% CO2 was compared to that during continuous administration of 3% CO2 in nine adult dogs anesthesized with sodium pentobarbital. Thirteen experiments with oscillating CO2 and eighteen with steady CO2 were performed. In all except one animal the increase in ventilation per mm Hg change in mean PaCOCO2 was greater during intermittent CO2 than during steady CO2. In three experiments intermittent administration of CO2 caused a ventilatory response sufficient to lower the mean PaCOCO2 below control values. The increment in total ventilation per mm Hg rise in arterial carbon dioxide tension for steady CO2 breathing was 0.58 liters/min per mm Hg and for intermittent CO2 was 2.00 liters/min per mm Hg. These findings support the concept that chemoreceptors are stimulated by oscillations of PaCOCO2 as well as by the mean level of PaCOCO2. The oscillatory stimulus appears not to be related to the amplitude of the oscillation or to the peak Pco2 attained, but rather to the rate of increase of arterial Pco2. respiration control; ventilation Submitted on October 17, 1963

In excised lungs of dogs, the static pressure-volume characteristics of the vascular bed were determined with the vessels filled with dextran and again after replacement of the dextran with kerosene. Whereas the dextran was distributed throughout the entire vascular bed, the kerosene was distributed only in relatively large vessels due to interfacial tension. Volume-pressure curves obtained with kerosene were markedly different from those obtained with dextran. Utilizing both types of volume-pressure curves, it was possible to separate the vascular bed of the lung into two compartments that responded oppositely to inflation of the lung when vascular pressure was held constant: one compartment, consisting of relatively large vessels, always increased in volume; the other compartment, consisting of smaller vessels, always decreased in volume. Submitted on June 9, 1960

Collection of expired-air carbon monoxide (CO) samples was utilized to examine inspectors on the United States-Mexican border to determine if significant increases in carboxyhemoglobin (COHb) occur. Twenty-six border inspectors were categorized as to smoking habits and work shift CO exposures. Employees not actively engaged in car inspection duties constituted the control group. Following shifts when particularly high ambient CO levels persisted, significant increases in COHb were noted in both smokers and non- smokers. Controls did not exhibit significant alterations in COHb levels. The hazards of such COHb elevations to exposed individuals are discussed in light of recent evidence of a lack of threshold for cardiovascular and central nervous system effects.

The efficiency with which airborne test organisms were removed from the lower part of a room when the upper air was irradiated with ultraviolet light (UV) was used to evaluate convective air mixing between the upper and lower parts of the room. The temperature of air entering the room through four diffusers in the ceiling was 10 to 15 F hotter or colder than lower room air during the studies. Rates of disappearance of test organisms atomized into the air were more than twice as fast when cold air entered at the ceiling as when hot air entered. Mean vertical mixing rates were estimated to be 20 air changes per hour (AC/hr) with hot air entering at the ceiling and 150 to 300 AC/hr with cold air entering at the ceiling. These large differences resulted from the large temperature gradients which favored or inhibited vertical mixing of air.

Experiments have been performed to determine the effect of viscose rayon fibers upon the pulmonary mechanics of a group of rats. Daily intratracheal injection of synthetic fiber suspension for 20 days produced an increase in index of alveolar pressure and a decrease in tidal volume, respiratory rate, and minute volume. In control animals there was no significant change in pulmonary function after intratracheal injection of normal saline. Comparison of the values after the first exposure of rayon fibers with those after intra tracheal injection of histamine did not show significant difference except in higher respiratory rate after histamine. In both exposed and control groups, infection was present when the animals were killed at the end of the experiment. The significant changes in lung function in control animals with approximately the same histological findings indicated that the changes in dust-exposed animals were mostly related to the rayon fibers.

A rebreathing method was used to study the increase in ventilation with an increase in PaCOCO2 in newborn infants and adults. The response curve of infants was shifted to the left of that of adults, which is consistent with their lower initial PaCOCO2 and buffer base, and greater metabolism per kilogram of body weight. The rebreathing response curves of infants were also to the left of steady-state responses reported by others. It is postulated that nonchemical stimuli caused higher ventilation throughout the entire range of the CO2 response curves in the infants studied by rebreathing without altering the sensitivity to increases in Pco2. The change in ventilation per kilogram versus the change in PaCOCO2, the slopes of the CO2 response curves, were nearly the same in infants and adults studied by either method. This finding, when the comparison is made on the basis of body weight, suggests the sensitivity of the regulatory apparatus does not change with age, and the output of the effector apparatus, lungs and chest wall, is related to the mass of the individual. CO2 response curves; nonchemical stimuli; chemical stimuli; respiration Submitted on February 19, 1963

Ventilation and end-tidal Pco2 were studied in six subjects awake and asleep (following the ingestion of 200–300 mg sodium pentobarbital) during oxygen breathing and the administration and withdrawal of 4% CO2 in oxygen. During the control period as well as steady-state CO2 breathing, ventilation was significantly lower in asleep than in awake subjects. There was no significant difference between sleep and wakefulness in end-tidal Pco2 or in the slope of the ventilatory response to 4% CO2. The transient responses of ventilation and end-tidal Pco2 of the group as a whole were similar in sleep and wakefulness. Ventilation changed more slowly than did end-tidal Pco2. End-tidal Pco2 overshot beyond the steady-state CO2 breathing value at the onset of CO2 breathing; and undershot below the control value during recovery. The magnitudes of both the overshoot and undershoot of end-tidal Pco2 were correlated significantly to the slope of the ventilatory response to 4% CO2, in the whole group awake and asleep. Submitted on October 4, 1962

It was shown that in excised lungs of dogs the effect of changing the degree of inflation of the lung was to change the static volume-pressure curve of the pulmonary vascular bed in shape, slope, and position. The data show that there is no simple answer to the question: does the pulmonary vascular bed get bigger or smaller with inflation of the lung? If vascular pressure was held constant when transpulmonary pressure was changed from 0 to 30 cm H2O, vascular volume increased when vascular pressure was low and decreased when vascular pressure was high. In addition, when vascular pressure was held constant, vascular volume changed in an opposite way depending on whether transpulmonary pressure was changed from low to moderate values or from moderate to high values. Submitted on June 9, 1960

This study attempted to evaluate the relative roles of vessel distensibility and vessel recruitment in the changes in pulmonary blood volume induced by changes in pulmonary intravascular pressure. Pulmonary blood volume was determined by a double-injection indicator-dilution technique in eight anesthetized open-chest dogs with a right and left ventricular bypass which allowed independent control of pulmonary artery and left atrial pressures. In three dogs, measurements were also taken during reverse perfusion (from the left atrium to the pulmonary artery). During forward perfusion, when left atrial pressure was increased from 7 to 26 cm H 2 O, and, by reducing flow from 3.4 to 1.2 liters'/min, pulmonary artery pressure was maintained at 30 cm H 2 O so that recruitment could be considered constant, pulmonary blood volume did not change but remained at about 260 ml. Pulmonary blood volume also did not change during reverse perfusion when pulmonary artery pressure was increased from 8 to 27 cm H 2 O at a constant left atrial pressure (inflow pressure). By contrast, when pulmonary artery pressure was raised by increasing flow, so that vessel recruitment could occur, pulmonary blood volume increased 12 ml for each 1-cm H 2 O increase in pulmonary artery pressure at a constant left atrial pressure of 5 cm H 2 O, and pulmonary blood volume increased 7 ml for each 1-cm H 2 O increase in pulmonary artery pressure at a constant left atrial pressure of 33 cm H 2 O. Therefore, in the range of pressures that we explored, the role of large-vessel distensibility in the changes in pulmonary blood volume observed when intravascular pressures were raised was small.