A BIOCHEMICAL STUDY OF ISOLATED PERFUSED LUNGS WITH SPECIAL REFERENCE TO THE EFFECTS OF PHOSGENE

Abstract

Control Perfused Lungs.‐The biochemical changes in the blood which is perfusing isolated lungs can for the most part be accounted for by the blood concentration. Concentration occurs to a slight extent immediately perfusion is started and proceeds at a considerably greater rate after 2‐4 hours of perfusion. We have no evidence as to the cause of the early stage of concentration, but it may be due to the loss of water by passage through the visceral plasma and in some experiments by formation of lymph. Rapid and late concentration is almost certainly due to the formation of œdema fluid. The progressive changes in the plasma chlorides on the one hand and in plasma protein on the other indicate that the chlorides leave the plasma earlier than the proteins. The composition of œdema fluid as regards the more diffusible chloride and the less diffusible protein may be determined in part by the rate of evaporation of the cedema fluid within the lungs, and therefore by the degree of lung ventilation, as well as by the rate at which the capillaries become more and more permeable to the larger molecules. These factors have to be taken into account when comparing the constituents of final samples of plasma with those of the œdema fluid.Without prejudicing the responsibility of other factors, we wish to stress, as others have done before us, the probability that the abnormal state of the perfusion fluid accounts for the capillary damage. The perfusion fluid is heparinised blood which our experience leads us to believe more nearly approaches normal blood in its effect on the lungs than does defibrinated blood. Notwithstanding, heparinised blood on passage through the lungs quickly loses its leucocytes which are held up as clumps in the smaller blood‐vessels of the lung [ Bickford and Winton, 1934; Trowell, 1943]. We associate this phenomenon with the observation that in some samples of heparinised blood which has been passed through the lungs the leucocytes are found clumped together. As perfusion progresses, the proportion of irregularly shaped red cells increases and those which remain spherical and smooth in their greatest axis are reduced in diameter. That a toxic factor is responsible both for this blood picture and for the capillary damage is not unlikely. The conditions of its formation and its nature are not known. It may be identical with the so‐called “vasotonin” or the “bronchotonin” substance.Perfused Lungs Exposed to Phosgene.‐With this background of our control perfused lung we have been able to test the effects of phosgene on the other lung perfused under identical conditions. The result has been that doses of phosgene sufficient to cause desquamation of the bronchial mucosa, severe bronchoconstriction, and an increase in the circulating blood volume of the lungs, exert no significant effects (as compared with the control lung) on the physico‐chemical state of the blood, on the histological blood picture, on the pulmonary vascular bed, or on the rate of onset of œdema.Various interpretations of this result occur to us, none of which has yet been tested. They may be enumerated with brief comment.1. It might be argued that in an experiment of 7‐8 hours the full effects of even very large doses of phosgene on the lungs have not time to become manifested, for in our experience of phosgene‐gassed living dogs there is a latent period of 8‐10 hours after gassing before clinical signs of œdema appear. This indeed may be the correct interpretation of our results. If so, it is clear that the conditions under which isolated lungs are perfused cause cedema before phosgene œdema has time to appear, and thus isolated perfused lungs are unsuitable for testing the effects of phosgene administration on lung tissues. We are not, however, inclined to accept this interpretation without further evidence.2. That the severe bronchoconstriction without a compensatory increased respiratory effort effectively prevents high concentrations of phosgene from having contact with the alveoli for any significant length of time.3. That the lung tissues and capillaries in perfused lungs differ in respect of their phosgene reactivity from those of normal lungs. How far the absence of functionally active nerves to isolated lungs may be responsible for this difference requires examination.We wish to acknowledge our indebtedness to Dr. O. A. Trowell for the histological examination of the lungs, to the Ministry of Supply for facilities and for permission to publish the results, and to the Moray Endowment Committee for defraying part of the expenses of the research.