Fibrin Deposition in the Rabbit Kidney Produced by Protease Inhibitors

Summary

The infusion of thrombin and the proteolytic inhibitors EACA, AMCHA, PAMBA, Trasylol, Soya and Lima bean trypsin inhibitor as well as ovomucoid, resulted in fibrin deposition in the glomerulus of the rabbit. The distribution is similar in may respects to that observed in the GSP. Renal cortical necrosis did not occur and the fibrin was apparently lysed 24 hrs after infusion. At that time the inhibitors have disappeared from the tissues. It is assumed that the inhibition of the fibrinolytic enzyme system due to these substances, produces a potentiation of thrombin and, therefore, intravascular coagulation. The animals were partly defibrinated without significant alteration in circulating platelets. If several inhibitors were used together, the action was additive and not synergistic was observed. The experiments indicate that the mechanism of fibrin deposition in the rabbit is related to the fibrinolytic capacity of the organism in addition to other factor and is not merely a function of RES blockade (32).

^* Career Scientist of the Health Research Council of the City of New York, under contract 1-127.

^** Career Scientist of the Health Research Council for the City of New York, under contract 1-303.

• References

• 1 Naeye R. L. Thrombotic state after hemorrhagic diathesis a possible complication with epsilon amino caproic acid. Blood 19: 694 1962;
• 2 Beller F. K. Treatment of coagulation disorders in pregnancy. Clin. Obstet. Gynec 7: 372 1964;
• 3 Lee L. Reticuloendothelial clearance of circulating fibrin in the pathogenesis of the generalized Shwartzman reaction. J. exp. Med 115: 1065 1962;
• 4 Margaretten W, Zunker H. O, McKay D. G. Intravenous infusion of thrombin. J. Lab. Invest 13: 552 1964;
• 5 Ratnoff O. D, Menzie C. A new method for the determination of fibrinogen in small samples of plasma. J. Lab. clin. Med 37: 316 1951;
• 6 Johnson A. J, Tse A. O. Caseinolytic and fibrinolytic assay for plasminogen (proteolytic precursor) in human purified plasminogen preparations or biological fluids. In Tocantins L. M, Kazal A. L. Blood coagulation and hemorrhage and thrombosis. Grune and Stratton; New York: 1964
• 7 Johnson A. J, Tse A. O, Newman J. Fibrinolytic determination of plasmin inhibitor in purified systems or biological fluids. ibid. P. 481.
• 8 Hartert H. Die Thrombelastographie. Eine physikalische Analyse des Blutgerinnungs-vorganges. Z. exp. Med 177: 189 1951;
• 9 Todd A. S. The histological localization of fibrinolysis activator. J. Path. Bact 78: 281 1959;
• 10 Beller F. K, Epstein M. D, Kaller H. Half life, distribution and placental transfer of pancreatic trypsin inhibitor. Thromb. Diathes. haemorrh. (Stuttg.) 16: 302 1966;
• 11 Okamoto S, Okamoto U. A new potent antifibrinolytic substance and its effects on blood of animals. Keio J. Med 11: 105 1962;
• 12 Markwardt F, Hanstein K. O, Kloeckening H. Die pharmakologische Charakterisierung des neuen Antifibrinolyticums P-Amin o Methylbenzoesäure (PAMBA). Arch, intern. Pharma-codyn 252: 223 1964;
• 13 Marx R, Hennig H. Über Verstärker Substanzen der Antifibrinoly se Wirkung der E-ACS im Organismus. Proceed. 8 Kongr. Europ. Ges. Haemat. Wien. 454 Karger; Basel: 1962
• 14 Beck E, Schmutzler R, Duckert F. Inhibition of fibrinolysis and fibrinogenolysis in man. Comparison of E-amino-caproic and Kallikrein Inhibitor. Thrombos. Diathes. haemorrh. (Stuttg.) 10: 106 1963;
• 15 Markwardt F, Klocking H. P, Richter H. Die Kombinationswirkung von Fibrinolyse Hemmstoffen. Acta biol. med. germ 12: 522 1964;
• 16 Johnson A. J, Tillet W. S. The lysis in rabbits of intravascular blood clots by the streptococcal fibrinolytic system. J. exp. Med. N. Y 95: 449 1952;
• 17 Fukuda T. Seasonal variations in endotoxin susceptibility of rabbits. Jap. J. Physiol 15: 240 1963;
• 18 Bohle A. Elektronenmikroskopische Untersuchungen am Glomerulum des Kaninchens beim generalisierten Shwartzman Phenomenon. Verh. dtsch. Ges. Path. 41. Tag. 1957. Fischer; Stuttgart: 1958
• 19 McKay D. G. Disseminated intravascular coagulation. Hoeber; New York: 1964
• 20 Fletcher A. P, Alkjaersig N, Sawyer W. D. E - Amino-Caproic-Acid: A potent Antifibrinolytic agent. Trans. Ass. Amer. Phys 72: 62 1959;
• 21 Kunitz M, Northrop J. H. Isolation from beef pancreas of trypsinogen, trypsin, A trypsin Inhibitor and an inhibitor trypsin compound. J. gen. Physiol 19: 991 1936;
• 22 Kraut H, Bhargava N, Schultz F, Zimmermann H. Versuche zur Isolierung des Kallikrein Inaktivators. Z. physiol. Chem 334: 230 1963;
• 23 Maki M, Beller F. K. Comparative study of fibrinolytic inhibitors in vitro. Thrombos. Diathes. haemorrh. (Stuttg.) 16: 600 1966;
• 24 Hjort P. F. A critical review of the evidence for a continuous hemostasis in vivo.Thrombos. Diathes. haemorrh. (Stuttg.) 6: 580 1961;
• 25 Lasch H. G, Rodriguez-Erdman F. The Sanarelli-Shwartzman Phenomenon as related to blood coagulation. Thrombos. Diathes. haemorrh. (Stuttg.) 7: 205 1962;
• 26 Kleinmayer H, Goergen K, Lasch H. G, Krecke H. J, Bohle A. Untersuchungen zur Frage der Gerinnungsstörung beim Sanarelli-Shwartzman Phenomen. Z. exp. Med 132: 275 1959;
• 27 Thomas L, Bronson J. G, Smith R. T. Studies on the generalized Shwartzman reaction. J. exp. Med 102: 249 1955;
• 28 Good R. A, Thomas L. Studies on the generalized Shwartzman reaction. IV. Prevention of the local and generalized Shwartzman reactions with heparin. J. exp. Med 97: 871 1953;
• 29 Des Prez R. M, Horowitz K. I, Hook E. W. Effects of bacterial endotoxin on rabbit platelets. I. Platelet aggregation and release of platelet factors in vivo. J. exp. Med 114: 857 1961;
• 30 Epstein M. D, Beller F. K. Species specificity of tissue activator in pregnant and nonpregnant organisms. Fed. Proc. 1966.
• 31 McKay D. G, Shapiro S. S. Alterations in the blood coagulation system induced by bacterial endotoxin. J. exp. Med 107: 353 1958;
• 32 Prose P. H, Lee L, Balk S. D. Electron microscopic study of the phagocytic fibrin-clearing mechanism. Amer. J. Pathol 47: 403 1965;