Constants of the Alper and Howard-Flanders oxygen equation for damage to bacterial membrane, deduced from observations on the radiation-induced penicillin-sensitive lesion

Energy deposited in the bacterial envelope of E. coli B/r induces lesions which are lethally attacked by penicillin in concentration insufficient to affect unirradiated bacteria. The critical lesions are probably in the membrane moiety. Bacteria were irradiated in the presence of 100 per cent oxygen, oxygen-free nitrogen and mixtures of 1.01, 0.59, 0.3, 0.1 and 0.06 per cent oxygen in nitrogen. Changes in sensitivity with pO2 conformed with the Alper and Howard-Flanders equation, for bacteria treated after irradiation by penicillin as well as for the untreated ones. The values of m were respectively 4.8 and 3.3; the values of K were identical, within experimental error, i.e. 4.4 mmHg. Sensitivity to induction of the penicillin-sensitive lesion was calculated from the difference in the reciprocals of D0 values proper to untreated and treated bacteria, for every gas used. The value of m could not be directly calculated because the effect of penicillin on anoxically irradiated bacteria was not detectable. For that reason, a transformation of the oxygen equation was used which allowed estimates to be made of both m and K, provided the results conformed with the equation. Within experimental error they did so conform. The calculated values of m and K for induction of the penicillin-sensitive lesion were respectively 8 and 5.9 mmHg, but it is shown that the oxygen enhancement ratio was probably underestimated and the K value overestimated. On the assumptions that these values of m and K are specific for radiation damage to bacterial membrane, and that radiation-induced killing is attributable to lethal lesions in the membrane as well as the DNA, the results demonstrate that any interaction of oxygen with sites of energy deposition in the DNA must play a very much smaller role in radiosensitization than does interaction with sites of energy deposition in the membrane.     

Adding two components of radiosensitization by oxygen

It has been shown, or inferred, in various contexts that radiosensitization of cells by oxygen is the sum of two (or more) components. If the component sensitivities conform with the Alper and Howard-Flanders equation their sum cannot also conform, but, in practice, even the most meticulous experimental techniques will fail to reveal lack of conformity unless one of the component K values is at least nine times the other. Thus, despite the many results that have demonstrated conformity with the equation, the existence of at least two components may well be a general phenomenon. The killing of cells by radiation is attributable to a summation of lesions in different structures; different K values for the contributing components are therefore to be expected, since neither oxygen nor its competitors are likely to be present in uniform concentration in all elements of the cell nucleus. Provided the components have intrinsic values of o.e.r. greater than one, their addition results in sensitivity that increases monotonically with PO2, approaching asymptotically to the overall o.e.r. which is a weighted average of the component o.e.r.s. In a curve plotted with PO2 on a linear scale a point of inflection can occur only if one component o.e.r. has a value less than one (i.e. oxygen is protective for that component), and then only if relationships between the other parameters satisfy certain conditions. In cases in which points of inflection in the sensitivity curve has been observed these are unlikely to be accounted for by the addition of two components. The analysis of the consequences of adding two components of oxygen sensitization could apply also to chemical sensitization of hypoxic cells.     

Measurement of hypoxia using the comet assay correlates with preirradiation microelectrode pO2 histography in R3327-AT rodent tumors

Polarographic determination of tumor oxygenation by Eppendorf histography is currently under investigation as a possible predictor of radiotherapy outcome. Alternatively, the alkaline comet assay has been proposed as a radiobiological approach for the detection of hypoxia in clinical tumor samples. Direct comparisons of these methods are scarce. One earlier study with different murine tumors could not establish a correlation, whereas a weak correlation was reported for a variety of human tumors. Considering the different end points and spatial resolution of the two methods, a direct comparison for a single tumor entity appeared desirable. Anaplastic R3327-AT Dunning prostate tumors were grown on Copenhagen rats to volumes of 1-6 cm(3). Eppendorf histography (100-200 readings in 5 parallel tracks) for 8 different tumors revealed various degrees of oxygenation, with median pO(2) values ranging from 1.1 to 23 mmHg. Within 5 min after an acute exposure to 8 Gy (60)Co gamma rays, tumors were excised from killed animals and rapidly cooled to limit repair, and a single cell suspension was prepared for use with the comet assay. The resulting comet moment distributions did not exhibit two subpopulations (one hypoxic and the other aerobic), and a hypoxic fraction could not be calculated. Instead, the average comet moment distribution was taken as a parameter of overall strand break induction. Corresponding experiments with tumor cells grown in vitro allowed us to derive the relationship between the oxygen enhancement ratio (OER) for the average comet moment and oxygen partial pressure (Howard-Flanders and Alper formula). The validity of this relationship was inferred for cells exposed in situ, and the convolution of a pO(2) distribution with the formula of Howard-Flanders and Alper yielded an array of expected OER values for each tumor. The average expected OER correlated well with the average comet moment (r = 0.89, P < 0.01), and the in situ comet moment distributions could be predicted from the Eppendorf data when 50% repair was taken into account, assuming a 5-min damage half-life. The findings confirm the potential of interstitial polarography to reflect radiobiologically relevant intracellular oxygenation, but also underscore the confounding influence of differences in repair that may occur when cells are prepared from irradiated tissues for use with the comet assay.     

Pores of Kohn are filled in normal lungs: low-temperature scanning electron microscopy.

Interalveolar pores of Kohn, small uniform-sized epithelium-lined openings in alveolar walls of normal lung, have historically been demonstrated with electron-microscopic techniques that remove water. We show these pores to be present but almost invariably filled with material when water and surfactant are preserved in frozen hydrated lung examined with low-temperature scanning electron microscopy. In the normal mouse, 16 open empty pores per alveolus were found in instillation-fixed dried lung vs. less than 1 per alveolus in frozen hydrated lungs (P less than 0.001). In the normal rat, 13 pores were seen per alveolus in instillation-fixed dried lung vs. less than 1 per alveolus in frozen hydrated lungs (P less than 0.001). We suggest that pores of Kohn 1) function primarily as conduits for interalveolar movement of alveolar liquid, surfactant components, and macrophages, 2) provide distributed sites for tubular myelin storage without increasing gas diffusion pathway thickness in the alveolar subphase itself, and 3) do not function as pathways for collateral ventilation during normal breathing in the absence of atelectasis or obstruction.     

A simplified method for determining the P50 of blood.

A method to determine the P50 of whole blood is described using a modified American Optical reflectance oximeter, pump, and membrane tonometer, together with PO2, PCO2, and pH measurements in a standard blood gas machine. Determinations of P50 were made in 66 patients and normal subjects and in two situations where P50 was very low and very high. The results were compared to oxygen saturations calculated from measured oxygen content. The directly determined oxygen saturation agreed with the assumed saturation of 50 per cent in the oximeter within 0.5 per cent. The apparatus appears to be a simple and relatively inexpensive method to obtain P50 as long as blood carboxyhemoglobin or methemoglobin contents are not elevated.     

Metabolic and ventilatory responses to hypoxia in two altitudinal populations of the toad, Bufo bankorensis

Effects of hypoxia on resting oxygen consumption (MO2), lung ventilation, and heart rate at different ambient PO2 were compared between lowland and high altitude populations of the toad, Bufo bankorensis. Resting MO2 decreased significantly in mild hypoxia (PO2 = 120 mm Hg) at 10 degrees C and in moderate hypoxia (PO2 = 80 mm Hg) at 25 degrees C in both altitudinal populations; however, resting MO2 did not differ significantly between the two populations. Numbers of lung ventilation periods (VP) and total inspired volume (VL) did not change with PO2 at 10 degrees C, but did increase at moderate and severe hypoxia (40 mm Hg), respectively, at 25 degrees C. Resting heart rates did not change during hypoxia and did not differ between altitude populations. The results suggest (1) the effect of PO2 change on MO2 should be considered in future studies involving transfer of anurans to a different altitude; and (2) the metabolic and ventilatory physiology in B. bankorensis does not compensate for the low temperature and PO2 at high altitude.     

Latency to CNS oxygen toxicity in rats as a function of PCO2 and PO2

Central nervous system (CNS) oxygen toxicity can occur as convulsions and loss of consciousness, without any premonitory symptoms. We have made a quantitative study of the effect of inspired carbon dioxide on sensitivity to oxygen toxicity in the rat. Rats were exposed to four oxygen pressures (PO(2); 456, 507, 608 and 709 kPa) and an inspired partial pressure of carbon dioxide (PCO(2)) in the range 0-12 kPa until the appearance of the electroencephalograph first electrical discharge (FED) that precedes the clinical convulsions. Exposures were conducted at a thermoneutral temperature of 27 degrees C. Latency to the FED decreased linearly with the increase in PCO(2) at all four PO(2) values studied. This decrease, which is probably related to the cerebral vasodilatory effect of carbon dioxide, reached a minimal value that remained constant on further elevation of PCO(2). The slopes (absolute value) and intercepts of latency to the FED as a function of carbon dioxide decreased with the increase in PO(2). This log-linear relationship made possible the derivation of equations that describe latency to the FED as a function of both PO(2) and PCO(2) in the PCO(2) - dependent range: Latency (min) = e((5.19-0.0040)(P)(O(2)))-e((2.77-0.0034)(P)(O(2))) x PCO(2) (kPa), and in the PCO(2)-independent range: Latency(min) = e((2.44-0. 0009)(P)(O(2))). A PCO(2) as low as 1 kPa significantly reduced the latency to the FED. It is suggested that in closed-circuit oxygen diving, any accumulation of carbon dioxide should be avoided in order to minimize the risk of CNS oxygen toxicity.     

Modeling pulmonary and CNS O(2) toxicity and estimation of parameters for humans.

The power expression for cumulative oxygen toxicity and the exponential recovery were successfully applied to various features of oxygen toxicity. From the basic equation, we derived expressions for a protocol in which PO(2) changes with time. The parameters of the power equation were solved by using nonlinear regression for the reduction in vital capacity (DeltaVC) in humans: %DeltaVC = 0.0082 x t(2)(PO(2)/101.3)(4.57), where t is the time in hours and PO(2) is expressed in kPa. The recovery of lung volume is DeltaVC(t) = DeltaVC(e) x e(-(-0.42 + 0.00379PO(2))t), where DeltaVC(t) is the value at time t of the recovery, DeltaVC(e) is the value at the end of the hyperoxic exposure, and PO(2) is the prerecovery oxygen pressure. Data from different experiments on central nervous system (CNS) oxygen toxicity in humans in the hyperbaric chamber (n = 661) were analyzed along with data from actual closed-circuit oxygen diving (n = 2,039) by using a maximum likelihood method. The parameters of the model were solved for the combined data, yielding the power equation for active diving: K = t(2) (PO(2)/101.3)(6.8), where t is in minutes. It is suggested that the risk of CNS oxygen toxicity in diving can be derived from the calculated parameter of the normal distribution: Z = [ln(t) - 9.63 +3.38 x ln(PO(2)/101.3)]/2.02. The recovery time constant for CNS oxygen toxicity was calculated from the value obtained for the rat, taking into account the effect of body mass, and yielded the recovery equation: K(t) = K(e) x e(-0.079t), where K(t) and K(e) are the values of K at time t of the recovery process and at the end of the hyperbaric oxygen exposure, respectively, and t is in minutes.     

The influence of oxygen on the induction of radiation damage in DNA in mammalian cells after sensitization by intracellular glutathione depletion

Treatment of mammalian cells with buthionine sulphoximine (BSO) or diethyl maleate (DEM) results in a decrease in the intracellular GSH (glutathione) and non-protein-bound SH (NPSH) levels. The effect of depletion of GSH and NPSH on radiosensitivity was studied in relation to the concentration of oxygen during irradiation. Single- and double-strand breaks (ssb and dsb) and cell killing were used as criteria for radiation damage. Under aerobic conditions, BSO and DEM treatment gave a small sensitization of 10-20 per cent for the three types of radiation damage. Also under severely hypoxic conditions (0.01 microM oxygen in the medium) the sensitizing effect of both compounds on the induction of ssb and dsb and on cell killing was small (0-30 per cent). At somewhat higher concentrations of oxygen (0.5-10 microM) however, the sensitization amounted to about 90 per cent for the induction of ssb and dsb and about 50 per cent for cell killing. These results strengthen the widely accepted idea that intracellular SH-compounds compete with oxygen and other electron-affinic radiosensitizers with respect to reaction with radiation-induced damage, thus preventing the fixation of DNA damages by oxygen. These results imply that the extent to which SH-compounds affect the radiosensitivity of cells in vivo depends strongly on the local concentration of oxygen.     

The importance of NPSH on the radiosensitizing effect of oxygen in Chinese hamster V-79 cells

The radiosensitivity of Chinese hamster V-79-171B fibroblasts increased more rapidly with increasing partial pressure of oxygen when the cell cultures had low endogenous levels of non-protein sulphydryl (NPSH), about 5 mumol per cell compared with about 15 mumol per cell. There was a good correlation between initial NPSH content and sensitization by oxygen concentrations between 0.06 and 0.7 per cent.     

The Effect of Respiratory Inhibitors and Chelating Agents on the Frequencies of Chromosomal Aberrations Produced by X-Rays in Vicia

Nitrosophenylhydroxylamine-ammonium (cupferron), potassium cyanide, sodium azide, ethylenediaminetetraacetate (EDTA), α,α'-dipyridyl, and o-phenanthroline were tested (1) for their ability to enhance the frequencies of chromosomal aberrations produced by x-rays in the root tip cells of the broad bean, Vicia faba, and (2) for their ability to inhibit oxygen consumption of excised roots of the same plant. In all cases a close correlation was found between the inhibitory effect on respiration and the enhancement of the sensitivity to x-rays at low oxygen pressures. EDTA, dipyridyl, and o-phenanthroline did not affect respiration to any greater extent, and they were without influence on the radiosensitivity. Cyanide, azide, and cupferron, which strongly inhibited respiration, also increased the frequencies of chromosome aberrations produced by x-rays at low oxygen pressures. The relation between oxygen concentration and radiosensitivity was determined both in the presence and the absence of the respiratory inhibitor cupferron. When cupferron was present, the radiosensitivity was influenced by oxygen concentrations 30 times lower than those effective in the absence of the inhibitor. In an atmosphere of pure oxygen, an increase of radiosensitivity of about 20 per cent was obtained with cupferron, EDTA, and potassium cyanide.     

Effect of acute hypoxia on microcirculatory and tissue oxygen levels in rat cremaster muscle.

Repeated exposure to brief periods of hypoxia leads to pathophysiological changes in experimental animals similar to those seen in sleep apnea. To determine the effects of such exposure on oxygen levels in vivo, we used an optical method to measure PO2 in microcirculatory vessels and tissue of the rat cremaster muscle during a 1-min step reduction of inspired oxygen fraction from 0.21 to 0.07. Under control conditions, PO2 was 98.1 +/- 1.9 Torr in arterial blood, 52.2 +/- 2.8 Torr in 29.0 +/- 2.7-microm arterioles, 26.8 +/- 1.7 Torr in the tissue interstitium near venous capillaries, and 35.1 +/- 2.6 Torr in 29.7 +/- 1.9-microm venules. The initial fall in PO2 during hypoxia was significantly greater in arterial blood, being 93% complete in the first 10 s, whereas it was 68% complete in arterioles, 47% at the tissue sites, and 38% in venules. In the 10- to 30-s period, the fall in normalized tissue and venular PO2 was significantly greater than in arterial PO2. At the end of hypoxic exposure, PO2 at all measurement sites had fallen very nearly in proportion to that in the inspired gas, but tissue oxygen levels did not reach critical PO2. Significant differences in oxyhemoglobin desaturation rate were also observed between arterial and microcirculatory vessels during hypoxia. In conclusion, the fall in microcirculatory and tissue oxygen levels in resting skeletal muscle is significantly slower than in arterial blood during a step reduction to an inspired oxygen fraction of 0.07, and tissue PO2 does not reach anaerobic levels.     

Lobar contribution to VA/Q inequality during constant-flow ventilation

Previous studies have shown that normal arterial PCO2 can be maintained during apnea in anesthetized dogs by delivering a continuous stream of inspired ventilation through cannulas aimed down the main stem bronchi, although this constant-flow ventilation (CFV) was also associated with a significant increase in ventilation-perfusion (VA/Q) inequality, compared with conventional mechanical ventilation (IPPV). Conceivably, this VA/Q inequality might result from differences in VA/Q ratios among lobes caused by nonuniform distribution of ventilation, even though individual lobes are relatively homogeneous. Alternatively, the VA/Q inequality may occur at a lobar level if those factors causing the VA/Q mismatch also existed within lobes. We compared the efficiency of gas exchange simultaneously in whole lung and left lower lobe by use of the multiple inert gas elimination technique in nine anesthetized open-chest dogs. Measurements of whole lung and left lower lobe gas exchange allowed comparison of the degree of VA/Q inequality within vs. among lobes. During IPPV with positive end-expiratory pressure, arterial PO2 and PCO2 (183 +/- 41 and 34.3 +/- 3.1 Torr, respectively) were similar to lobar venous PO2 and PCO2 (172 +/- 64 and 35.7 +/- 4.1 Torr, respectively; inspired O2 fraction = 0.44 +/- 0.02). Switching to CFV (3 l.kg-1.min-1) decreased arterial PO2 (112 +/- 26 Torr, P less than 0.001) and lobar venous PO2 (120 +/- 27 Torr, P less than 0.01) but did not change the shunt measured with inert gases (P greater than 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)     

RESPIRATORY EFFECTS UPON THE VISUAL THRESHOLD

Measurements are reported of the effects of respiratory stresses upon the absolute threshold of peripheral (rod) vision. Since subjects were kept wholly dark adapted and the photochemical system of the rods therefore stationary, the changes recorded may be assumed to have originated more centrally. To this degree the measurements provide a quantitative index of central nervous imbalance. Breathing room air or 32 to 36 per cent oxygen at about double the normal rate causes the visual threshold to fall to approximately half the normal value within 5 to 10 minutes. This change is due primarily to alkalosis induced by the hyperventilation, and can be abolished or reversed by adding carbon dioxide to the inspired mixtures. Normal or rapid breathing of 2 per cent carbon dioxide causes no change in threshold; with 5 per cent carbon dioxide the threshold is approximately doubled. Breathing 10 per cent oxygen at the normal rate also approximately doubles the threshold. This effect is compensated in part by rapid breathing. When 10 per cent oxygen is breathed at twice the normal rate the threshold usually falls at first, then slowly rises to supernormal levels. Due primarily to variations in their breathing patterns subjects yield characteristically different responses on sudden exposure to low oxygen tensions with breathing uncontrolled. The threshold may either rise or fall; and on release from anoxia it may rise, or fall to normal or subnormal levels. The threshold adjusts to anoxia rapidly; exposures lasting 5 to 6 hours do not produce greater or more persistent changes than those of much shorter duration.     

The effect of inspired oxygen concentration on the ventilation-perfusion distribution in inhomogeneous lungs

The coupled conservation of mass equations for oxygen, carbon dioxide and nitrogen are written down for a lung model consisting of two homogeneous alveolar compartments (with different ventilation-perfusion ratios) and a shunt compartment. As inspired oxygen concentration and oxygen consumption are varied, the flux of oxygen, carbon dioxide and nitrogen across the alveolar membrane in each compartment varies. The result of this is that the expired ventilation-perfusion ratio for each compartment becomes a function of inspired oxygen concentration and oxygen consumption as well as parameters such as inspired ventilation and alveolar perfusion. Another result is that the "inspired ventilation-perfusion ratio and the "expired ventilation-perfusion ratio differ significantly, under some conditions, for poorly ventilated lung compartments. As a consequence, we need to distinguish between the "inspired ventilation-perfusion distribution, which is independent of inspired oxygen concentration and oxygen consumption, and the "expired ventilation-perfusion distribution, which we now show to be strongly dependent on inspired oxygen concentration and less dependent oxygen consumption. Since the multiple inert gas elimination technique (MIGET) estimates the "expired ventilation-perfusion distribution, it follows that the distribution recovered by MIGET may be strongly dependent on inspired oxygen concentration.     

The 1988 Stevenson Memorial lecture. Physiological responses to severe hypoxia in man

Recent measurements at extreme altitude and in low pressure chamber simulations have clarified the human responses to extreme hypoxia. Man can only tolerate the severe oxygen deprivation of great altitudes by an enormous increase in ventilation which has the advantage of defending the alveolar PO2 against the reduced inspired PO2. Nevertheless the arterial PO2 on the Everest summit is less than 30 Torr (1 Torr = 133.3 Pa). An interesting consequence of the hyperventilation is that the respiratory alkalosis greatly increases the oxygen affinity of the hemoglobin and assists in oxygen loading by the pulmonary capillary. The severe hypoxemia impairs the function of many organ systems including the central nervous system, and there is evidence of residual impairment of memory and manipulative skill in climbers returning from great altitudes. At the altitude of Mt. Everest, maximal oxygen uptake is reduced to 20-25% of its sea level value, and it is exquisitely sensitive to barometric pressure. It is likely that the seasonal variation of barometric pressure affects the ability of man to reach the summit without supplementary oxygen.     

A test of the oxidative damage hypothesis for discontinuous gas exchange in the locust Locusta migratoria

The discontinuous gas exchange cycle (DGC) is a breathing pattern displayed by many insects, characterized by periodic breath-holding and intermittently low tracheal O(2) levels. It has been hypothesized that the adaptive value of DGCs is to reduce oxidative damage, with low tracheal O(2) partial pressures (PO(2) ≈ 2-5 kPa) occurring to reduce the production of oxygen free radicals. If this is so, insects displaying DGCs should continue to actively defend a low tracheal PO(2) even when breathing higher than atmospheric levels of oxygen (hyperoxia). This behaviour has been observed in moth pupae exposed to ambient PO(2) up to 50 kPa. To test this observation in adult insects, we implanted fibre-optic oxygen optodes within the tracheal systems of adult migratory locusts Locusta migratoria exposed to normoxia, hypoxia and hyperoxia. In normoxic and hypoxic atmospheres, the minimum tracheal PO(2) that occurred during DGCs varied between 3.4 and 1.2 kPa. In hyperoxia up to 40.5 kPa, the minimum tracheal PO(2) achieved during a DGC exceeded 30 kPa, increasing with ambient levels. These results are consistent with a respiratory control mechanism that functions to satisfy O(2) requirements by maintaining PO(2) above a critical level, not defend against high levels of O(2).     

Pulmonary gas exchange in Andean natives with excessive polycythemia--effect of hemodilution

Pulmonary gas exchange in Andean natives (n = 8) with excessive high-altitude (3,600-4,200 m) polycythemia (hematocrit 65.1 +/- 6.6%) and hypoxemia (arterial PO2 45.6 +/- 5.6 Torr) in the absence of pulmonary or cardiovascular disease was investigated both before and after isovolemic hemodilution by use of the inert gas elimination technique. The investigations were carried out in La Paz, Bolivia (3,650 m, 500 mmHg barometric pressure). Before hemodilution, a low ventilation-perfusion (VA/Q) mode (VA/Q less than 0.1) without true shunt accounted for 11.6 +/- 5.5% of the total blood flow and was mainly responsible for the hypoxemia. The hypoventilation with a low mixed venous PO2 value may have contributed to the observed hypoxemia in the absence of an impairment in alveolar capillary diffusion. After hemodilution, cardiac output and ventilation increased from 5.5 +/- 1.2 to 6.9 +/- 1.2 l/min and from 8.5 +/- 1.4 to 9.6 +/- 1.3 l/min, respectively, although arterial and venous PO2 remained constant. VA/Q mismatching fell slightly but significantly. The hypoxemia observed in subjects suffering from high-altitude excessive polycythemia was attributed to an increased in blood flow perfusing poorly ventilated areas, but without true intra- or extrapulmonary shunt. Hypoventilation as well as a low mixed venous PO2 value may also have contributed to the observed hypoxemia.     

Quantitative observations on the pulmonary anatomy of the domestic Muscovy duck (Cairina moschata)

The lungs of five female domestic Muscovy ducks, mean body weight 1.627 kg, total lung volume 48.07 cm³, were analysed by standard morphometric methods. Principal results obtained are: lung volume per unit body weight, 30.17 cm³/g; volume densities of exchange tissue relative to lung volume, 49.24%, blood capillaries relative to exchange tissue, 29.63%, tissue of the blood gas (tissue) barrier relative to exchange tissue, 5.88%; surface area of the blood-gas (tissue) barrier per unit body weight, 30.04 cm²/g; ratios of the surface area of the blood-gas (tissue) barrier per unit volume of the lung and per unit volume of exchange area, 979 cm²/cm³ and 200.06 mm²/mm³, respectively; harmonic and arithmetic mean thicknesses of the tissue barrier, 0.199 μm and 0.303 μm, respectively. The anatomical diffusing capacity of the tissue barrier for oxygen ( DtO₂ ) and the total pulmonary diffusing capacity ( DLO₂ ), 49.58 ml O₂/min/mmHg/kg and 4.55 ml O₂/min/mm Hg/kg, respectively. The lungs of the domestic Muscovy duck appear to be about as well adapted anatomically for gas exchange as the lungs of wild anatid species, and there is no clear evidence that domestication has been associated with any deterioration in the anatomical capacity for oxygen uptake. The weight-specific anatomical diffusing capacity of the lung for oxygen ( DLO₂/W ) was about 3.6 times greater than the weight-specific physiological value, a factor which falls within the expected range.     

Role of barometric pressure in pulmonary fluid balance and oxygen transport

To examine the role of barometric pressure in high-altitude pulmonary edema, we randomly exposed five unanesthetized chronically instrumented sheep with lung lymph fistulas in a decompression chamber to each of three separate conditions: hypobaric hypoxia, normobaric hypoxia, and normoxic hypobaria. A combination of slow decompression and/or simultaneous adjustment of inspired PO2 provided three successive stages of simulated altitudes of 2,600, 4,600, and 6,600 m during which hemodynamics and lymph flow were monitored. Under both hypoxic conditions we noted significant and equivalent elevations in pulmonary arterial pressure (Ppa), cardiac output, and heart rate, with left atrial and systemic pressures remaining fairly constant. Normoxic hypobaria was also accompanied by a smaller but significant rise in Ppa. Lymph flow increased to a highly significant maximum of 73% above base line, accompanied by a slight but significant decrease in lung lymph-to-plasma protein ratio, only under conditions of combined hypobaric hypoxia but not under equivalent degrees of alveolar hypoxia or hypobaria alone. Arterial hypoxemia was noted under all three conditions, with arterial PO2 being uniformly lower under hypobaric conditions than when identical amounts of inspired PO2 were delivered at normal atmospheric pressure. We therefore hypothesize that alveolar pressure significantly alters the Starling forces governing transcapillary fluid flux in the lung and may affect the alveolar-arterial gradient for O2 as well.