PHYSIOLOGIC IMPORTANCE OF LYMPH 



I°53 



was elevated only slightly above plasma oncotic 

 pressure. It was observed onlv after a considerable 

 elevation of left atrial pressure, above plasma oncotic 

 pressure, was maintained for a period of one-half hour 

 or more. Chronic elevation of left atrial pressure was 

 achieved in 15 dogs. Left atrial mean pressure varied 

 from 10 to 23 mm Hg. The dogs were followed for 10 

 months. Right lymphatic flow did not increase at 

 chronically elevated mean pressure below 25 mm Hg. 

 They did not study flow at higher pressures because 

 they were unable to sustain left atrial mean pressure 

 above 25 mm Hg in any dog in the chronic group. 

 The animals that were brought to left atrial mean 

 pressure between 30 to 40 mm Hg, and in which these 

 high levels were presumably maintained, were found 

 dead in their cages with pulmonary edema 1 to 2 days 

 after the snare was tightened. 



Drinker, while admitting that hemodynamic 

 changes might be responsible for pulmonary edema, 

 stressed the importance of changes in capillary per- 

 meability due to anoxia (60). He believed that "in- 

 creased pressure in the pulmonary capillaries does not 

 readily cause recognizable pulmonary edema unless 

 coupled with heightened permeability, most fre- 

 quently due to anoxia." His conclusions were based 

 on a variety of experiments by him and his group (65, 

 216, 217). Thus, forced breathing of dogs against re- 

 sistance without hypoxia did not cause pulmonary- 

 edema, although right duct lymph flow was aug- 

 mented. On the other hand, when anoxia was present 

 under the same circumstances, increased lymph flow 

 and pulmonary edema were evident. Increased capil- 

 lary filtration, according to Drinker, results in ac- 

 cumulation of fluid in the alveoli, interfering with 

 oxygen uptake. A vicious cycle is set up as the hypoxia 

 further increases capillary permeability and filtration. 

 Courtice & Korner (48), on the other hand, failed to 

 observe pulmonary edema when they made animals 

 breathe a mixture containing 1 1 per cent oxygen. 

 They believe that the results of the Drinker group can 

 be equally well explained by postulating an increase 

 in filtration pressure rather than changes in capillary 

 permeability. There is considerable evidence to indi- 

 cate that the permeability of systemic capillaries does 

 not change at the levels of anoxia produced in the 

 Drinker and in the Courtice and Korner experiments, 

 and the latter correctly conclude that there is no 

 evidence to indicate that the permeability character- 

 istics of the pulmonary capillaries are different with 

 respect to anoxia. Courtice and Korner gave large 

 infusions of Ringer-Locke's solution to rabbits breath- 

 ing low oxygen. The presence of anoxia led to edema 



at a lower level of infusion than when anoxia was not 

 present. The authors believe that this effect can be 

 explained by the hemodynamic changes observed 

 (decrease in cardiac output, systemic vasoconstriction, 

 etc.) without postulating an increase in permeability. 

 It may be pertinent in this connection, however, that 

 Fishman et al. (71) recently reported that acute anoxia 

 in human subjects produces a rise in cardiac output 

 and that significant changes in pulmonary arterial 

 pressure (average 7 mm Hg) are not found except 

 when the arterial blood oxygen saturation is below 

 85 per cent. It also appears that acute hypoxia does 

 not affect the thoracic blood volume (80). 



The conclusions of Courtice and Yoffey should also 

 perhaps be modified in light of more recent findings 

 in our laboratory (197). We injected radioactive 

 iodinated serum albumin and dextran fractions of 

 average molecular weights of 51,000 to 255,000 into 

 dogs anesthetized with Nembutal and followed con- 

 centration changes in plasma and thoracic and right 

 duct lymphs for 4 to 6 hours. At this time, when a 

 "steady state" had been established between plasma 

 and lymph, we infused 40 ml per kg of 5 per cent 

 serum albumin in 0.9 per cent saline. This resulted 

 in a significant and striking increase in the concentra- 

 tion of the injected radioactive iodinated albumin and 

 dextrans in right duct and thoracic duct lymph in 

 spite of increased lymph flows. We interpreted these 

 results (and earlier ones) to be the result of "stretch- 

 ing" of capillary pores as a result of raised hydrostatic 

 pressure resulting from the expanded blood volume. 

 It is conceivable that the hypoxia in Courtice and 

 Korner's experiments may have served to exaggerate 

 this phenomenon of the capillary wall. It is interesting, 

 in this connection, that the possibility of pore stretch- 

 ing was suggested by Casten & Kistler (40) as an ex- 

 planation of the acute pulmonary edema which they 

 observed in mice and rats following blast injury and 

 irradiation. They hypothesized: "The intercellular 

 cement substance of capillary walls is postulated to 

 consist of processes having elastic properties that tie 

 the cell walls together. These processes are assumed 

 to be normally under tension. If the intracapillarv 

 pressure increases, but remains below a critical value, 

 the tension of the intercellular processes may be still 

 sufficient to hold the cell mosaic tightly together and 

 prevent gross fluid leakage. If the internal pressure 

 exceeds this critical value, then the elastic processes 

 may be stretched to a degree which causes the cell 

 mosaic to be separated, and thereby permit gross fluid 

 effusion to occur. With still greater internal pressure, 

 the processes may be stretched beyond their elastic 



