Anticoagulant Properties of Rabbit Lungs in Tissue Thromboplastin-induced Intravascular Coagulation

Summary

This study was conducted in order to examine possible anticoagulant properties of the lungs during tissue thromboplastin-induced intravascular coagulation. Rabbit brain tissue thromboplastin (n = 17) or saline (n = 6 + 3) was infused above the right atrium (n = 11 + 3) of the heart or in the arcus aorta (n = 6) for a period of 120 min in non-pregnant New Zealand rabbits. Rabbits infused with tissue thromboplastin responded with significantly (p <0.05) more excessive changes in a number of haemodynamic variables (heart rate, p_aO₂> p_aCO₂, blood pH etc.) compared with rabbits infused with saline.

Similarly, the prothrombin time (p <0.05) and the activated partial thromboplastin time (p <0.05) were significantly more prolonged in rabbits receiving tissue thromboplastin compared with control animals. Also the concentration of blood platelets (p<0.05), plasma fibrinogen (p <0.05), antithrombin (p <0.05), and protein C (p <0.05) decreased significantly in thromboplastin-treated animals compared with control animals. In all these haemostatic variables there was a common trend that animals infused with tissue thromboplastin in the arcus aorta responded more excessively than animals infused in the right atrium of the heart, and these deviations were statistically significant for fibrinogen (p <0.05) and prothrombin time (p <0.05). Similarly, animals infused with tissue thromboplastin in the arcus aorta had an increased number of microthrombi in the lungs and kidneys compared with animals receiving tissue thromboplastin above the right atrium.

As the lungs are the first pass organ when you infuse above the right atrium the results from this study suggest that the lungs play a key role in protecting the organism against excessive tissue thromboplastin-induced activation of coagulation.

• References

• 1 Hardaway RM. Organ damage in shock, disseminated intravascular coagulation, and stroke. Compr Ther 1992; 18: 17-21
• 2 Hardaway RM, Williams CH, Marvasti M, Farias M, Tseng A, Pinon I, Yanez D, Matinez M, Navar J. Prevention of adult respiratory distress syndrome with plasminogen activator in pigs. Crit Care Med 1990; 18: 1413-1418
• 3 Hardaway RM. Disseminated intravascular coagulation and the treatment of adult respiratory distress syndrome with plasminogen activators. Hematology Reviews 1994; 09: 03-19
• 4 Saldeen T. The microembolism syndrome: a review. In: The microembolism syndrome. Saldeen T. (ed). lStockholm: Almqvist & Wiksell International; 1979. pp 07-44
• 5 Astrup T. Fibrinolysis and tissue repair in the lungs. In: The microembolism syndrome. Saldeen T. (ed). Stockholm: Almqvist & Wiksell International; 1979. pp 45-71
• 6 Saldeen T. Fibrin derived peptides and pulmonary injury. NY Acad Sci 1982; 384: 319-331
• 7 Malik AB, Johnson A, Tahamont MV. Mechanism of lung vascular injury after intravascular coagulation. NY Acad Sci 1982; 384: 213-234
• 8 Idell S, James KK, Levin EG, Schwartz BS, Manchanda N, Maunder RJ, Martin TR, McLarty J, Fair DS. Local abnormalities in coagulation and fibrinolytic pathways predispose to alveolar fibrin deposition in the adult respiratory syndrome. J Clin Invest 1984; 84: 695-705
• 9 Idell S, Koenig KB, Fair DS, Martin TR, McLarty J, Maunder RJ. Serial abnormalities of fibrin turnover in evolving adult respiratory distress syndrome. Am J Physiol 1991; 261: L240-248
• 10 Gram J, Janetzko T, Jespersen J, Bruhn HD. Enhanced effective fibrinolysis after heparin neutralization in open-heart surgery increases the risk of post-surgical bleeding. Thromb Haemost 1990; 63: 241-245
• 11 Albrechtsen OK, Brakman P, Astrup T. The defibrination syndrome in rabbits following infusion of tissue thromboplastin in the jugular vein. Thromb Diath Haemorrh 1970; 24: 113-128
• 12 Jespersen J, Sidelmann J. A study of the conditions and the accuracy of the thrombin time assay of plasma fibrinogen. Acta Haematol 1992; 67: 2-7
• 13 Gram J, Jespersen J. Increased concentration of heparin cofactor II in diabetic patients, and possible effects on thrombin inhibition assay of antithrombin III. Clin Chem 1989; 35: 52-55
• 14 Lendrum AC. The staining of erytrocytes in tissue sections A new method and observations on some of the modified Mallory connective tissue stains. J Path Bact 1949; 61: 443-448
• 15 Matthews JNS, Douglas GA, Campbell MJ, Royston P. Analysis of serial measurements in medical research. Br Med J 1990; 300: 230-235
• 16 Muller-Berghaus G. Pathophysiologic and biochemical events in disseminated intravascular coagulation. Dysregulation of procoagulant and anticoagulant pathways. Semin Thromb Hemost 1989; 15: 58-87
• 17 Triantaphyllopoulos DC. Effects of human antithrombin on mortality and blood coagulation induced in rabbits by endotoxin. Thromb Haemost 1984; 51: 232-235
• 18 Paloma MJ, Paramo JA, Rocha E. Effect of DDAVP on endotoxin-induced intravascular coagulation in rabbits. Thromb Haemost 1992; 68: 306-309
• 19 Johnson A, Garcia-Szabo R, Kaplan JE, Malik AB. Fibrin degradation products increase lung transvascular fluid filtration after thrombin-induced pulmonary microembolism. Thromb Res 1985; 37: 543-554
• 20 Kaminski M, McDouagh J. Inhibited thrombins. Interactions with fibrinogen and fibrin. Biochem J 1987; 242: 881-887
• 21 Kaminski M, Siebenlist KR, Mosesson MW. Evidence for thrombin enhancement of fibrin polymerization that is independent of its catalytic activity. J Lab Clin Med 1991; 117: 218-225
• 22 Wilner GD, Danitz MP, Mudd MS, Hsieh K, Fenton IIJW. Selective immobilization of α-thrombin by surface-bound fibrin. J Lab Clin Med 1981; 97: 403-411
• 23 Novotny WF. Tissue factor pathway inhibitor. Semin Thromb Hemost 1994; 20: 101-108
• 24 Sandset PM, Wam-Cramer BJ, Rao LVM, Maki SL, Rapaport SI. Depletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation induced with tissue factor: evidence supporting a physiologic role of EPI as a natural anticoagulant. Proc Natl Acad Sci USA 1991; 88: 708-712
• 25 Sandset PM, Wam-Cramer BJ, Maki SL, Rapaport SI. Immunodepletion of extrinsic pathway inhibitor sensitizes rabbits to endotoxin-induced intravascular coagulation and the generalized Shwartzman reaction. Blood 1991; 78: 1496-1502
• 26 Busch C, Saldeen T. Amount of fibrin in different organs after intravenous intraportal and intraaortal injection of thrombin in the rat. Thromb Diath Haemorrh 1973; 29: 87-93