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A proposed study for the prevention of pulmonary emboli
Vob?%? Number
66 4
Annotations
because of the higher pressure inside than outside the cabin at high altitudes is carefully prevented by a filling of spongy rubber inside the walls for automatic sealing of punctures. The arterial lumen is always filled by blood with a pressure which is over 100 mm. Hg higher than that outside the artery. The spongy structure of the arterial wall has evolved for automatic sealing of punctures, and, in addition, the automatic sealing mechanism is temporally strengthened by emergency filling of plasma-like substance into the extracelluler space of the arterial wall by epinephrine; this is the “filling reaction” of arterial walls. Part of the body’s reaction to trauma is the sensation of pain, which is accompanied, of course, by an outpouring of epinephrine. Simultaneously, there may be a release of fatty materials. At times the amounts of fat released may be so great as to give rise to the clinical manifestation of fat embolism. In an experimental study6 in which rabbits and monkeys were used, we demonstrated that fats of animal origin6 such as lanolin, lard, rabbit fat, butyric acid, palmitic acid, stearic acid, and cholesterol, produced the generalized platelet sticking reaction and filling reaction of arterial walls when administered as a single oral “dose.” When epinephrine was also given, the two reactions became much stronger and long lasting. Fats of vegetable origin had no such effect. In an additional investigation6 the hindleg of the rabbit was traumatized 15 or 16 days after complete surgical denervation. This painless traumatization powerfully induced the platelet sticking reaction and the filling reaction, and also enhanced blood coagulability. I submit that Cannon’s “emergency reaction” should be expanded to include the filling reaction and the platelet sticking reaction, and I should also like to make the additional significant observation that fats of animal origin initiate and also potentiate these reactions. We have so far been unable to define the chemical nature of the mechanism which acts directly on the walls of the blood vessels to produce these effects.
The filling reaction may well be a key mechanism in atherogenesis. The morphologic characteristics of the artery under these conditions stimulate das in&‘&e fettfreie tjdernr of the German school, which has been proposed, since Virchow, as the first stage in atherogenesis. Moreover, we6 have found substances, synthesized by Professor Ishikawa, which are capable of preventing the filling reaction, as well as atherosclerosis in cholesterol-fed rabbits, and which have a striking effect in the prevention of experimental thrombosis. Elaboration of these studies appears to be important in the search for the basic pathophysiologic mechansims of thrombosis and of atherosclerosis. Takio Shimamoto, M.D. Institute for Cardiowascular Diseases Tokyo Medical and Dental University 3-Chome, Yushimu, Bunkyo-Ku Tokyo, Japan REFERENCES 1. Cannon, W. B.: The wisdom of the body, New York, 1939, W. W. Norton. 2. Shimamoto, T.: Effect of adrenaline and noradrenaline on “silicone-like property” of blood vessels, Proc. Japan Acad. 36:234, 1960. 3. Shimamoto, T.: Acute vascular endothelial reaction, Asian M. J. 4:311, 1961. 4.. Shimamoto, T., and Sunaga, T.: Edematous arterial reaction by adrenaline and cholesterol and its prevention by MAO inhibitor observed by electron microscopic technique, Jap. Heart J. 3581, 1962. 5. Shimamoto, T.: The relationship of edematous reaction in arteries to atherosclerosis and thrombosis. 1. Atherosclerosis Res. fin mess). 6. Deuel, H. J.; Jr.: The lipids, New York: 195i, Interscience Publisher, Inc., Vol. I, pp. 184207. 7. Schettler, G.: Arteriosklerose, Atiologie, Pathologie, Klinik, und Therapie, Stuttgart, 1961, Georg Thieme Verlag, p. 11.
A proposed study for the prevention of pulmonary
Pulmonary emboli kill thousands of people each year. The following ideas are submitted as a proposal for diminishing the morbidity and fatality rates due to this disorder. Upon returning to Los Angeles after training in the East, one of the authors was greatly impressed by the relatively few cases of pulmonary emboli seen in Los Angeles. San Francisco also has relatively few cases of pulmonary infarctions. Other
573
emboli
internists who have previously worked in the East have had the same impression. Observations made on rounds at Harvard and at New York and London hospitals seemed to indicate that pulmonary emboli were common and often a cause of death. The impression was that innumerable patients at the Massachusetts General Hospital had had their femoral veins ligated. There also appeared to be more instances of emboli in winter than in summer.
574
Annotations
Whether or not our impression is correct, the following studies would be relevant on physiologic grounds. The first study, although less feasible, may be mentioned: Take two similar wards, each containing approximately the same type of case. Keep one ward relatively zuar~, and see that the patients have plenty of blankets. Keep the other ward relatively cool, so that the patients’ lower extremities might be a little cold, but without subjecting the patients to discomfort. The patients in the warm ward should have an extra amount of fluid and salt. The incidence of pulmonary emboli in the relatively z~rrn ward may be found to be significantly reduced in comparison to the incidence in the cooler ward. Meticulous care of room temperatures, body temperatures, skin temperatures (especially of the lower extremities) must, of course, be observed. The second study seems practical. There might be some objections to warming the entire patient, especially if he is in shock, or suffers from hypoxia or cardiac or respiratory disorders. The more feasible project would be to warm the lower extremities. This could be done with an electric blanket with controlled temperature, or leggings of electricblanket material thermostatically regulated to enhance the peripheral circulation only, i.e., from foot to groin. The measurement of the femoral vein arterial oxygen saturation would be taken as an index of increased blood flow. Arterialized blood has already been obtained in this manner, i.e., 97 per cent oxygen saturation of brachial vein
Am. Heart I. October, 1963
blood. It would not be desirable to establish this maximum flow, but an oxygen saturation of venous femoral vein blood approximately 10 per cent higher than the central level, i.e., 75 to 80 per cent, The most feasible method of achieving enhanced local blood flow to the extremities is the thermostatically controlled leggings. If made in various sizes, they could be pulled on each extremity and kept there for 2 to 3 weeks before and 2 to 3 weeks after the operation, or until the patient becomes ambulatory. If the experiment could be set up in two or three hospitals, such as Veterans’ Hospitals in states in which cases of pulmonary emboli are frequent, it might be possible to obtain an answer at the end of a year or so’ This subject is manifestly more complicated than the single factor outlined. A statistical survey of the incidence of this dreaded complication in the cooler cities compared with its incidence in the warmer cities would also be relevant. Encouraging preliminary statistical information has already been obtained. Myron Pvinzmetal, M.D. Institute for Medical Research Cedars of Lebanon Hospital 4751 Fountain Ave. Los Angeles 29, Calif. and Aban L. Barach, M.D. Columbia-Presbyterian Medical Center New York, N. Y.
66 4
Annotations
because of the higher pressure inside than outside the cabin at high altitudes is carefully prevented by a filling of spongy rubber inside the walls for automatic sealing of punctures. The arterial lumen is always filled by blood with a pressure which is over 100 mm. Hg higher than that outside the artery. The spongy structure of the arterial wall has evolved for automatic sealing of punctures, and, in addition, the automatic sealing mechanism is temporally strengthened by emergency filling of plasma-like substance into the extracelluler space of the arterial wall by epinephrine; this is the “filling reaction” of arterial walls. Part of the body’s reaction to trauma is the sensation of pain, which is accompanied, of course, by an outpouring of epinephrine. Simultaneously, there may be a release of fatty materials. At times the amounts of fat released may be so great as to give rise to the clinical manifestation of fat embolism. In an experimental study6 in which rabbits and monkeys were used, we demonstrated that fats of animal origin6 such as lanolin, lard, rabbit fat, butyric acid, palmitic acid, stearic acid, and cholesterol, produced the generalized platelet sticking reaction and filling reaction of arterial walls when administered as a single oral “dose.” When epinephrine was also given, the two reactions became much stronger and long lasting. Fats of vegetable origin had no such effect. In an additional investigation6 the hindleg of the rabbit was traumatized 15 or 16 days after complete surgical denervation. This painless traumatization powerfully induced the platelet sticking reaction and the filling reaction, and also enhanced blood coagulability. I submit that Cannon’s “emergency reaction” should be expanded to include the filling reaction and the platelet sticking reaction, and I should also like to make the additional significant observation that fats of animal origin initiate and also potentiate these reactions. We have so far been unable to define the chemical nature of the mechanism which acts directly on the walls of the blood vessels to produce these effects.
The filling reaction may well be a key mechanism in atherogenesis. The morphologic characteristics of the artery under these conditions stimulate das in&‘&e fettfreie tjdernr of the German school, which has been proposed, since Virchow, as the first stage in atherogenesis. Moreover, we6 have found substances, synthesized by Professor Ishikawa, which are capable of preventing the filling reaction, as well as atherosclerosis in cholesterol-fed rabbits, and which have a striking effect in the prevention of experimental thrombosis. Elaboration of these studies appears to be important in the search for the basic pathophysiologic mechansims of thrombosis and of atherosclerosis. Takio Shimamoto, M.D. Institute for Cardiowascular Diseases Tokyo Medical and Dental University 3-Chome, Yushimu, Bunkyo-Ku Tokyo, Japan REFERENCES 1. Cannon, W. B.: The wisdom of the body, New York, 1939, W. W. Norton. 2. Shimamoto, T.: Effect of adrenaline and noradrenaline on “silicone-like property” of blood vessels, Proc. Japan Acad. 36:234, 1960. 3. Shimamoto, T.: Acute vascular endothelial reaction, Asian M. J. 4:311, 1961. 4.. Shimamoto, T., and Sunaga, T.: Edematous arterial reaction by adrenaline and cholesterol and its prevention by MAO inhibitor observed by electron microscopic technique, Jap. Heart J. 3581, 1962. 5. Shimamoto, T.: The relationship of edematous reaction in arteries to atherosclerosis and thrombosis. 1. Atherosclerosis Res. fin mess). 6. Deuel, H. J.; Jr.: The lipids, New York: 195i, Interscience Publisher, Inc., Vol. I, pp. 184207. 7. Schettler, G.: Arteriosklerose, Atiologie, Pathologie, Klinik, und Therapie, Stuttgart, 1961, Georg Thieme Verlag, p. 11.
A proposed study for the prevention of pulmonary
Pulmonary emboli kill thousands of people each year. The following ideas are submitted as a proposal for diminishing the morbidity and fatality rates due to this disorder. Upon returning to Los Angeles after training in the East, one of the authors was greatly impressed by the relatively few cases of pulmonary emboli seen in Los Angeles. San Francisco also has relatively few cases of pulmonary infarctions. Other
573
emboli
internists who have previously worked in the East have had the same impression. Observations made on rounds at Harvard and at New York and London hospitals seemed to indicate that pulmonary emboli were common and often a cause of death. The impression was that innumerable patients at the Massachusetts General Hospital had had their femoral veins ligated. There also appeared to be more instances of emboli in winter than in summer.
574
Annotations
Whether or not our impression is correct, the following studies would be relevant on physiologic grounds. The first study, although less feasible, may be mentioned: Take two similar wards, each containing approximately the same type of case. Keep one ward relatively zuar~, and see that the patients have plenty of blankets. Keep the other ward relatively cool, so that the patients’ lower extremities might be a little cold, but without subjecting the patients to discomfort. The patients in the warm ward should have an extra amount of fluid and salt. The incidence of pulmonary emboli in the relatively z~rrn ward may be found to be significantly reduced in comparison to the incidence in the cooler ward. Meticulous care of room temperatures, body temperatures, skin temperatures (especially of the lower extremities) must, of course, be observed. The second study seems practical. There might be some objections to warming the entire patient, especially if he is in shock, or suffers from hypoxia or cardiac or respiratory disorders. The more feasible project would be to warm the lower extremities. This could be done with an electric blanket with controlled temperature, or leggings of electricblanket material thermostatically regulated to enhance the peripheral circulation only, i.e., from foot to groin. The measurement of the femoral vein arterial oxygen saturation would be taken as an index of increased blood flow. Arterialized blood has already been obtained in this manner, i.e., 97 per cent oxygen saturation of brachial vein
Am. Heart I. October, 1963
blood. It would not be desirable to establish this maximum flow, but an oxygen saturation of venous femoral vein blood approximately 10 per cent higher than the central level, i.e., 75 to 80 per cent, The most feasible method of achieving enhanced local blood flow to the extremities is the thermostatically controlled leggings. If made in various sizes, they could be pulled on each extremity and kept there for 2 to 3 weeks before and 2 to 3 weeks after the operation, or until the patient becomes ambulatory. If the experiment could be set up in two or three hospitals, such as Veterans’ Hospitals in states in which cases of pulmonary emboli are frequent, it might be possible to obtain an answer at the end of a year or so’ This subject is manifestly more complicated than the single factor outlined. A statistical survey of the incidence of this dreaded complication in the cooler cities compared with its incidence in the warmer cities would also be relevant. Encouraging preliminary statistical information has already been obtained. Myron Pvinzmetal, M.D. Institute for Medical Research Cedars of Lebanon Hospital 4751 Fountain Ave. Los Angeles 29, Calif. and Aban L. Barach, M.D. Columbia-Presbyterian Medical Center New York, N. Y.