Thromb Haemost 1970; 24(01/02): 085-099
DOI: 10.1055/s-0038-1654214
Originalarbeiten – Original Articles – Travaux Originaux
Schattauer GmbH

Effects of Trans-4-Aminomethylcyclohexane Carboxylic Acid as an Antifibrinolytic Agent on Arterial Wall and Experimental Atherosclerotic Lesions in Rabbits

N Kato
*   Department of Pathology (Director: Prof. Munetomo Enjoji) , Faculty of Medicine, Kagoshima University, Kagoshima, Japan.
,
M Morimatsu
**   Department of Pathology (Director: Prof. Kenzo Tanaka), Faculty of Medicine, Kyushu University, Fukuoka, Japan.
,
K Tanaka
**   Department of Pathology (Director: Prof. Kenzo Tanaka), Faculty of Medicine, Kyushu University, Fukuoka, Japan.
,
A Horie
**   Department of Pathology (Director: Prof. Kenzo Tanaka), Faculty of Medicine, Kyushu University, Fukuoka, Japan.
› Author Affiliations
Further Information

Publication History

Publication Date:
24 July 2018 (online)

Summary

Effects of trans-4-aminomethylcyclohexane carboxylic acid (t-AMCHA) as an antifibrinolytic agent on the experimental arteriosclerosis produced by cholesterol feeding and on the experimental thromboembolism induced by autogenous fibrin clot injection were observed in rabbits. Effect of inhibited fibrinolysis on the arterial wall itself was also observed.

Administration of 500 mg/kg body weight of t-AMCHA highly inhibited the lysis time of serum, but there was no influence on the plasma fibrinogen level.

There was no significant difference in the cholesterol level, sudanophilia of the aorta and the accumulation of foam cells in the aorta and pulmonary arteries between t-AMCHA + cholesterol group and cholesterol group.

Edema in the subendothelial layer of the aorta and elastic pulmonary artery, proliferation and swelling of the endothelial cells, and edema of the subendothelial layer of large muscular pulmonary arteries were increased in the incidence and severity in t-AMCHA treated animals. Localized intimai fibrous thickening was found in large muscular artery in t-AMCHA treated animals. Small fibrin thrombi and angitis were rarely found in muscular pulmonary artery in t-AMCHA treated animals.

Fibrinolytic activity of blood and dissolution of clots in the pulmonary arteries were depressed by t-AMCHA treatment in the animals injected autogenous fibrin clots, while the inflammatory reaction in the arterial wall was less severe as compared with that of untreated animals.

It was reasonable to presume that the inhibition of fibrinolysis would promote the development of atherosclerosis through its influence on the fibrin dissolution on and in the arterial wall, and on the vascular permeability of the arterial wall.

 
  • References

  • 1 Astrup T. The biological significance of fibrinolysis. Lancet II: 565-568 1956;
  • 2 Astrup T, Müllertz S. The fibrin plate method for estimating fibrinolytic activity. Arch. Biochem 40: 346-351 1952;
  • 3 Becher J, Borgström S. Incidence of thrombosis associated with epsilon-aminocaproic acid and subcutaneous heparin therapy. A study in experimental animals and in clinical material. Acta chir. scand 134: 343-349 1968;
  • 4 Brunner E, Deutsch E. Einfluß der e-Aminocapronsäure auf die Ausbildung der Arteriosklerose beim Kaninchen. Yerh. dtsch. Ges. Inn. Med 70: 974-976 1964;
  • 5 Campbell R. S. F. Early atherosclerosis in the pig, a histological and histochemical study. J. atheroscler. Res 05: 483-496 1965;
  • 6 Copley A. L. Fibrinolysis and atherosclerosis. Lancet I: 102-103 1957;
  • 7 Crawford T, Levene C. I. The incorporation of fibrin in the aortic intima. J. Path. Bact 64: 523-528 1952;
  • 8 Dubber A. H, McNicol G. P, Douglas A. S. Amino methyl cyclohexane carboxylic acid (AMCHA) Anew synthetic fibrinolytic inhibitor. Brit. J. Haemat 11: 237-245 1965;
  • 9 Duguid J. B. Thrombosis as a factor in the pathogenesis of coronary atherosclerosis. J. Path. Bact 58: 207-212 1946;
  • 10 Duguid J. B. Thrombosis as a factor in the pathogenesis of aortic atherosclerosis. J. Path. Bact 60: 57-61 1948;
  • 11 Fritsch H, Czygan P, Kommerell B, Barth P. Effect of e-aminocaproic acid and b-amino- propionitrile of the nutritional atheromatosis of the rabbit. J. atheroscler. Bes 08: 811-820 1968;
  • 12 Greig H. B. W. Inhibition of fibrinolysis by alimentary lipaemia. Lancet II: 16-18 1956;
  • 13 Heard B. E. Mural thrombosis in the renal artery and its relation to atherosclerosis. J. Path. Bact 61: 635-637 1949;
  • 14 Herschlein H. J, Steichele D. F. Die Wirkung des Fibrinolyseinhibitors AMCHA auf die Blutgerinnung bei gesteigerter thromboplastischer Aktivität. Klin. Wschr 46: 102-106 1968;
  • 15 Kato N. Effects of epsilon aminocaproic acid on experimental atherosclerosis in rabbits. Fukuoka Acta med 58: 612-618 1967;
  • 16 Kwaan H. G, Astrujp T. Aortic arteriosclerosis in rabbits. Fed inhibitors of fibrinolysis. Arch. Path 78: 474-482 1964;
  • 17 Kwaan H. G, McFadzean A. J. S. Inhibition of fibrinolysis in vivo by feeding cholesterol. Nature (Lond.) 179: 260 1957;
  • 18 Lewis J. H, Ferguson J. H. Studies on proteolytic enzyme system of blood. I. Inhibition of fibrinolysin. J. clin. Invest 29: 486-490 1950;
  • 19 Momose T, Ueda Y, Yamamoto K, Masumura T, Ohta K. Determination of total cholesterol in blood serum with perchloric acid, phosphoric acid, ferric chloride reagent. Analyt. Chem 35: 1751-1753 1963;
  • 20 Movat H. Z, Haust M. D, More B. H. The morphologic elements in the early lesions of arteriosclerosis. Amer. J. Path 35: 93-97 1962;
  • 21 Naimi S, Loncin H, Wilgram G. F, Proger S. The relevance of lipemia and changes in blood coagulation and fibrinolysis to the pathologenesis of atherosclerosis and arterial thrombosis. In Memorias del IV Congress Mundial del Cardiologica. Mexico: 1962. IY-A, 258.
  • 22 Ohta G. Morphology of the vascular endothelium. An investigation of morphogenesis of incipient thrombosis. Acta path. Jap 10 (Suppl.) 377-394 1960;
  • 23 Okamoto S, Takada Y, Okamoto U. Antifibrinolytic activity of transform of AMCHA (4-Aminomethylcyclohexane-l-carboxylic acid_. J. Physiol. Soc. Japan 27: 207-213 1965;
  • 24 Oneda G, Yoshida Y, Takatama M, Sekiguchi M, Kato M. Effect of epsilon-aminocaproic acid as an antifibrinolytic agent on arterial lesions in hypertensive rats with surgically constricted renal arteries. Keio J. Med 11: 157-166 1962;
  • 25 Pryce D. M, Pike G, Gorrill R. H. A convenient method for producing embolic pulmonary lesions in rabbits. J. Path. Bact 62: 452-453 1950;
  • 26 Ratnoff O. D, Menzie C. A new method for the determination of fibrinogen in small samples of plasma. J. Lab. clin. Med 37: 316-320 1951;
  • 27 Studer A, Reber K, Lorez H. P. Experimentelle Untersuchungen zur Frage der Bedeutung intravasaler Fibrinabscheidung für die Entstehung arteriosklerotischer Wand Veränderungen. Path. Microbiol 27: 287-302 1964;
  • 28 Sumiyoshi A. Fibrin (fibrinogen) in the arterial wall and atherosclerosis. Fukuoka Acta med 59: 542-557 1968;
  • 29 Vick J. A, Branchard R. J, Perry Jr J. F. Effect of epsilon aminocaproic acid on pulmonary vascular changes produced by snake venom. Proc. Soc. exp. Biol. (N. Y.) 113: 841-844 1963;
  • 30 Wenger R, Krihaber E, Holzner H, Kaufmann F. Weitere tierexperimentelle Untersuchungen über die Arteriosklerose Entstehung. Z. Kreisl.-Forsch 52: 511-582 1963;
  • 31 Woolf N, Garstairs K. C. Infiltration and thrombosis in atherogenesis. A study using immunofluorescent techniques. Amer. J. Path 51: 373-381 1967;