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HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



The question as to whether capillary permeability 

 is altered in shock has been a hardy perennial. A 

 detailed discussion of this topic would be out of 

 place at this point. It is, however, appropriate to 

 call attention to the studies of the Hungarian group 

 referred to above in which they have made extensive 

 observations on the role of lymph and lymphatics in 

 dogs during and after traumatic shock. They have 

 used the same general approach as we have used 

 (141, 219) of introducing dextrans of molecular 

 weights similar to those of albumin and globulin into 

 the blood stream, following their disappearance from 

 the blood stream and their appearance in lymph from 

 various regions. Since radioisotopes were not available 

 to them, they used the dye, T-1824, which is known 

 to bind onto albumin and thus constitute a label. 

 Their results on control animals resemble in general 

 those which we obtained; albumin or de.xtran of 

 molecular weight of about 50,000 appeared in thoracic 

 duct lymph within 10 min and, in their experiments, 

 the average de.xtran concentration was 29 per cent 

 of that in plasma at 1 5 min and about 75 per cent at 

 60 to go min. In tourniquet shock produced by 

 arresting the circulation of the hind legs for 5 hours, 

 they found a more rapid disappearance of the dextran 

 from the blood stream but a much slower appearance 

 and accumulation in thoracic duct lymph. At 90 

 min there was only an average of 43 per cent of 

 dextran in the lymph. Lymph flow was considerably 

 reduced. These workers also studied cervical lymph 

 and, while their results were not definitive, it seems 

 reasonably certain that the capillary permeability in 

 peripheral regions was not increased. Attempts to 

 find the reasons for the decreased thoracic duct 

 lymph flow and the delayed appearance of protein 

 and dextran were not successful. It was apparently 

 not due to diminished hepatic-lymph formation or to 

 lymphangiospasm. They interpret the faster disap- 

 pearance of the dextran from blood as reflecting the 

 increase in capillary permeability in the ischemic 

 area rather than a generalized increase in perme- 

 ability. One of the group (226) has extended some 

 of the work to hemorrhagic and burn shock and 

 again finds a decreased thoracic duct lymph flow 

 which parallels the severity of the shock. He also 

 interprets his data as denying any generalized 

 increase in capillary permeability. 



Since edema is prominent in the ischemic areas, 

 these investigators went on to study the flow of leg 

 lymph and the behavior of albumin and dextran in 

 the hope of ascertaining whether the edema was due 

 to an inability of the lymphatic system to cope with 



an increased tissue fluid formation or whether there 

 was injury to the lymphatics caused by the ligatures. 

 Although the small lymph flow in leg lymphatics 

 precluded quantitative data, there was no question of 

 the direction of change and that protein leakage was 

 increased in the ischemic area. The increased lymph 

 flow argued against lymphatic injury or occlusion as 

 factors in the edema production. 



The occurrence of a vasoconstrictor substance in 

 blood during shock induced by trauma, hemorrhage, 

 and burns was reported in dogs by Page (161) and 

 denied for ischemic compression shock (91). Rapport 

 et al. (180) also reported the occurrence of a "toxic 

 factor" in tourniquet shock in rabbits. 



In 1943, Blalock (ig) reported the results of 

 experiments in which he produced crush injury in 

 anesthetized dogs by applying a press to a hind leg. 

 Thoracic duct lymph collected from these dogs after 

 removal of the pressure and injected into other dogs 

 brought on a decrease in blood pressure and death 

 of some of the animals. Less marked results were 

 obtained when trauma was produced by striking the 

 legs with a blunt instrument. Blalock explained his 

 results as due to the presence of a toxic substance in 

 lymph of the traumatized animals. Katzenstein 

 et al. (1 10) reported similar results in shock produced 

 by tourniquets around the hind legs. These authors 

 appreciated the possible vasodepressor effects of 

 large doses of Nembutal which they used but showed 

 that when narcosis was controlled to avoid vaso- 

 depression, injection of thoracic lymph from normal 

 dogs had no effect. In contrast, a fall in blood pressure 

 followed in 50 per cent of the animals injected with 

 lymph of shocked animals. The problem was further 

 studied by Nathanson and his collaborators (155), who 

 devised a method of producing tourniquet shock in 

 dogs which permitted the collection of muscle 

 exudate. They collected the exudate, which accumu- 

 lated after muscle anoxia, and injected it into the 

 same or recipient dogs (6). Shock was produced in 

 only 25 per cent of the animals tested. The incon- 

 stancy of the presence of the toxic factor suggested 

 that the factor was an extraneous agent, not present 

 in the usual cellular constituents and metabolic 

 products found in all muscle exudates, and possibly 

 bacterial in origin. They further showed (235) that 

 the toxic properties of a collection of pooled muscle 

 exudates were contained in a nondialyzable fraction, 

 could be salted out between 0.25 and 0.7 saturation 

 with ammonium sulfate and were, therefore, prob- 

 ably protein in nature. The toxic substances were 

 tentatively classified as an aminoexopeptidase and a 



