At any given time, the alveolar-arterial oxygen partial pressure difference (AaD) may be due to one or more of the three following mechanisms (1-5): 1) failure of pulmonary capillary blood to come to complete equilibrium with alveolar gas; 2) uneven ventilation perfusion ratios; and 3) admixture of venous blood by direct shunting.The first mechanism causes the diffusion component of the AaD, relating to diffusion across the alveolar-capillary membrane as well as chemical reaction rates of oxygen with hemoglobin (6, 7). The second mechanism accounts for the "distribution" component, and the third is spoken of as the "true," "pure," or "anatomical" shunt, or the "direct" venous admixture component.When the inspired oxygen tension is low, as at high altitude or during breathing of hypoxic mixtures, particularly if either condition is combined with exercise, the diffusion component increases, whereas those due to direct venous admixture and to uneven ventilation-perfusion ratios diminish. These changes are used to determine the pulmonary diffusing capacity for oxygen (1-3, 8).On the other hand, breathing 100% oxygen increases the AaD due to direct venous-arterial shunting, and virtually eliminates all other components (9).The role of diffusion impairment in the causation of arterial hypoxemia has been recently reevaluated ( 10), and a number of newer approaches have permitted a more precise definition of the distribution of ventilation-perfusion ratios and of its importance in gas exchange (11)(12)(13)(14)(15).

Induction of acute pulmonary edema in anesthetized dogs causes a large fall in compliance. out of proportion to lung volume (1), and a sharp increase in venous admixture that can be reversed by forcible inflation of the lungs (2). This pattern of abnormal function suggested alveolar closure (1, 2).Since alveolar stability depends in large measure on the presence of normal pulmonary surface properties (3), altered surface forces were consiclered as an underlying mechanism. Cook and co-workers (1) reasoned that the decrease in alv'eolar diameter, resulting from the accumulation of intra-alveolar fluid, would account for an increase in total surface forces. We examined the possibility that pulmonary edema alters alveolar surface tension properties, in this way contributing to alveolar instability and to the failure of respiratory function. It can 1)e shown that for alveoli, as for spherical surfaces, total surface forces equal twice the surface tension divided by the radius of curvature (4).We induced pulmonary edema in anesthetized dogs by rapid intravenous infusion of dextran. Surface activity of lung extracts was measured and correlated with morphologic changes. There was a regional loss or impairment of surface activity in the edematous lung, associated with areas * Submitted for publication October 14, 1964; accepted November 27, 1964. Presented in part at the 47th Annual Meeting of the American Physiological Society, April 15, 1963, Atlantic City, N. J., and abstracted in Fed. Proc. 1963, 22, 339. Supported by U. S. Public Health Service research grant HE-04226 and by a research grant from the American Heart Association. MethodsProccdnarc. The experiments were conducted on 24 mongrel dogs weighing 7 to 33 kg. The dogs were tracheostomized and anesthetized with 30 mg per kg pentobarbital intravenously. They were supine and breathed spontaneously or with the assistance of a Starling respirator, set to deliver ventilation in the normal tidal range. To duplicate the conditions of an earlier study of gas exchange in pulmonary edema (2), we gave the animals 100% oxygen to breathe before the induction of pulmonary edema; the total period of oxygen breathing was generally 1 to 2 hours and did not exceed 5 hours. Pulmonary edema was induced by intravenous infusion of 6%o dextran solution in saline, at the rate of approximately 4 ml per kg per minute. The infusion was maintained until foam came out of the trachea. The animals were then killed with magnesium sulfate.Post-mortem, the lungs were weighed separately and their gross morphologic features noted. In every case, one sample was taken from a dark, depressed part of the lung and another from a pink, relatively unaltered part. The samples were examined for surface activity, as detailed below. In seven instances, portions of these samples were also fixed in Bouin's solution and stained with hematoxylin and eosin, toluidine blue, and with periodic acid Schiff reagent for microscopic examination.In ten experiments, a thoracotomy was performed, and the airway t...

We examined pulmonary gas exchange in 19 anesthetized dogs during the induction of acute pulmonary edema by intravenous infusion of dextran in saline. We monitored pulmonary capillary pressure by a left atrial catheter, and arterial blood Po2 by an indwelling electrode. PaOO2 remained near normal until just before pulmonary edema was grossly apparent, when it fell precipitously; left atrial pressure mounted to a peak and then declined. The apparent “steady-state” DlCO was reduced as much as 61%, but the dominant cause of hypoxemia was an increased venous admixture (shunt flow) on O2 breathing. Since the shunt was reversible by forcible inflation of the lungs, induced pulmonary edema was probably associated with closure of alveolar units. pulmonary venous admixture (shunt flow) and diffusing capacity; alveolar closure; arterial blood oxygen; tension in vivo; hypoxemia Submitted on August 14, 1963

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