Experimental Model of Pulmonary Thrombosis in Rat

Summary

Experimental pulmonary thrombosis was induced in rats by intravenous infusion of 0.7 M lactic acid at a rate of 1.4 ml/100 g/hr for 2 hr. As acidosis progressed, a hyper-coagulable state developed and microthrombi were formed predominantly in the lung, but not conspicuously in other organs. Pulmonary thrombi thus formed were composed of aggregated platelets in the initial stage, and of fibrin in later stages. They progressively dissolved and had completely disappeared 12 hr after cessation of the lactic acid infusion.

During the infusion of lactic acid, the following changes were observed: progressive decreases in platelet count, fibrinogen, antiplasmin activity and fibrinolytic activity, and progressive increase in platelet adhesiveness. Plasma clotting time decreased to its shortest interval after one hour of the lactic acid infusion and remained at that level during the rest of the infusion. No fibrin degradation products (FDP) were detected.

After cessation of the lactic acid infusion, these parameters, except for fibrinolytic activity, tended to return to normal gradually while FDP increased markedly. Fibrinolytic activity measured by eugolobulin lysis time remained low, suggesting depletion of vascular activator. Plasminogen level began to fall gradually 6 hr after cessation of the lactic acid infusion.

These dynamic coagulo-fibrinolytic changes are discussed in relation to the morphological changes of thrombi.

• References

• 1 Abiko Y, Iwamoto M, Shimizu M. Plasminogen-Plasmin System I. Purification and properties of human plasminogen. Journal of Biochemistry 1968; 64: 743
• 2 Asada T, Igarashi M, Urita Y, Awazu S, Takeuchi S, Matsumoto M, Moroi M. A new technique for plasmin determination using affinity chromatography in the comparison with other methods. Journal of The Medical Society of Toho University 1972; 19: 549
• 3 Bicher H. I, Beemer A. Prevention by an antiadhesive drug of thrombosis caused by blood cell aggregation. Angiology 1971; 21: 413
• 4 Broersma R. J, Bullemer G. D, Mammen E. F. Blood coagulation changes in hemorrhagic shock and acidosis. Thrombosis et Diathesis Haemorrhagica Supplement 1969; 36: 171
• 5 Broersma R. J, BUllemer G. D, Mammen E. F. Acidosis induced disseminated intravascular microthrombosis and its dissolution by streptokinase. Thrombosis et Diathesis Haemorrhagica 1970; 24: 55
• 6 Busch C, Saldeen T. Amount of fibrin in difference organs after intravenous, intraportal and intraaortal injection of thrombin in the rat. Thrombosis et Diathesis Haemorrhagica 1973; 29: 87
• 7 Guseinov C. S, Rakhmaeva V. A, Rabinovich Y. Y, Chistyakov V. N. Participation of the lung in the process of fibrinolysis. Soviet Medicine 1971; 34: 18
• 8 Hartert H. Blutgerinnungsstudien mit der thrombelastographie, einem neuen untersuchungsverfahren. Klinische Wochenschrift 1948; 26: 577
• 9 Hladovec J. Experimental arterial thrombosis in rats with continuous registration. Thrombosis et Diathesis Haemorrhagica 1971; 26: 407
• 10 Iwamoto M, Abiko Y. Plasminogen-Plasmin System. IV. Preparation of α₂-macroglobulin antiplasmin from human plasma. Biochimica et Biophysica Acta 1971; 133: 374
• 11 Langdell R. D, Wagner R. H, Brinkhous K. M. Effect of antihemophilic factor on one-stage clotting time. Journal of Laboratory and Clinical Medicine 1953; 47: 637
• 12 Lowry O. H, Rosebrough N. J, Farr A. L, Randwall R. J. Protein measurement with the folin phenol reagent. Journal of Biological Chemistry 1951; 193: 265
• 13 Margaretten W, Csavossy L, McKay D. G. An electron microscopic study of thrombin induced disseminated intravascular coagulation. Blood 1967; 29: 169
• 14 McKay D. G, Linder M. M, Cruse V. K. Mechanisms of thrombosis of the microcirculation. American Journal of Pathology 1971; 63: 231
• 15 Merskey C, Kleiner G. J, Johnson A. J. Quantitative estimation of split products of fibrinogen in human serum, relation to diagnosis and treatment. Blood 1966; 28: 1
• 16 Nordöy A, Chandlar A. B. Platelet thrombosis induced by adenosine diphosphate in the rat. Scandinavian Journal of Haematology 1964; 1: 16
• 17 Norman P. S. Antiplasmins. Federation Proceedings 1966; 25: 63
• 18 Pflug J, Calnan J, Olsen G. J. An experimental model for the study of thrombosis. British Journal of Surgery 1968; 25: 63
• 19 Quick A. J, Stanly B. M, Bancroft F. W. A study of the coagulation defect in hemophilia and in jaundice. American Journal of Medical Sciences 1935; 190: 501
• 20 Rapaport S. I, Schiffman S, Patch J, Ware A. G. Simple, specific one-stage assay for plasma thromboplastin antecedent activity. Journal of Laboratory and Clinical Medicine 1961; 57: 771
• 21 Renaud S. Endotoxin-induced hepatic vein thrombosis in hyperlipemic rats. Sequence of events. Laboratory Investigation 1965; 14: 424
• 22 Roschlau W. H. E, Painter R. H. Human fibrinolysin with and without urokinase: its effect on experimental arterial thrombi in dog. Canadian Journal of Biochemistry and Physiology 1962; 40: 1819
• 23 Rø J. S, Flatmark A. Studies on thrombin infusion in dogs. Scandinavian Journal of Haematology 1972; 9: 293
• 24 Saldeen T. Experimental investigation on fat embolism and intravascular coagulation. Acta pathologica et microbiologica Scandinavia 1966; 66: 271
• 25 Salzman E. W. Measurement of platelet adhesiveness. Journal of Laboratory and Clinical Medicine 1963; 62: 724
• 26 Steinbuch M, Blatrix C, Josso F. α₂-Macrogiobulin as progressive antithrombin. Nature 1967; 216: 500
• 27 Shahbudin H. R, Raphael M. J. Therapeutic defibrination and heparin therapy in the prevention and resolution of experimental venous thrombosis. Circulation 1970; 42: 729
• 28 Speer R. J, Ridgway H. The formation and decay of XII_a . Thrombosis et Diathesis Haemorrhagica 1967; 18: 259
• 29 Stefanini M, Dameshek W. The Hemorrhagic Disorders. Grune & Stratton; New York: 1955: 149