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  IN THIS Article
 ::  Introduction
 ::  Material and methods
 ::  Results
 ::  Discussion
 ::  References

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Year : 1981  |  Volume : 27  |  Issue : 1  |  Page : 16-9

Clofibrate, fibrinolysis and experimental myocardial damage.







How to cite this article:
Saxena K K, Gupta B B, Srivastava R K, Singh R C, Prasad D N. Clofibrate, fibrinolysis and experimental myocardial damage. J Postgrad Med 1981;27:16


How to cite this URL:
Saxena K K, Gupta B B, Srivastava R K, Singh R C, Prasad D N. Clofibrate, fibrinolysis and experimental myocardial damage. J Postgrad Med [serial online] 1981 [cited 2019 Nov 19];27:16. Available from: http://www.jpgmonline.com/text.asp?1981/27/1/16/5669




  ::   Introduction Top

Clofibrate, a well known hypolipidaemic agent has drawn attention for over a past few years with regard to its efficacy in coronary artery disease. It has been shown to exert protective influence against the gross morbid effects in experimental myocardial infarction,[20] development of new infarction and sudden death in clinical cases.[2], [7], [10] Furthermore, it has recently been reported to reduce incidence and severity of arteriosclerosis,[6], [20] an important risk factor in precipitating myocardial infarction. However, the enthusiasm for prophylactic use of clofibrate has received a major setback following a five year U.S. multicenter study report regarding failure of clofibrate in reducing or preventing mortality in cardiovascular disorders.[19]
In view of the fact that altered fibrinolytic activity and plasma fibrinogen prevail following myocardial damage[4], [13], [14]. [16] and clofibrate influences fibrinolytic system[3], [5], [18] the present investigation was envisaged to explore its beneficial effects on fibrinolytic system in association with drug induced myocardial necrosis in rats.

  ::   Material and methods Top

Male Porter strain rats weighing 260 + 8 g were divided in four groups of ten animals each. Animals were fed on commercial rat diet and water was allowed ad libitum during the test period. Two groups of rats were fed clofibrate (100 mg/kg, suspended in 2% gum acacia, orally once daily) for seven consecutive days and the remaining two groups received matching volume of saline. One group each from clofibrate and saline treated animals was challenged with isoprenaline (85 mg/kg, s.c.) on day six and seven. On the eighth day, all the animals were anaesthetized with pentobarbitone sodium (40 mg/kg. i.p.) and blood samples were collected from the abdominal aorta in siliconized glass syringes for estimation of euglobulin clot lysis time (ECLT) I and plasma fibrinogen.[15] Hearts of isoprenaline challenged rats were dissected out and examined gross and microscopically. Cardiac lesions were graded from grade 0 to IV on a five point scale as described by Rona et al.[12]
Results were analysed by employing Student's `t' test and Fisher's exact probability test to calculate the level of significance.


  ::   Results Top

A. Effect of pretreatment with clofibrate on isoprenaline induced myocardial damage:
The distribution of grades of myocardial lesions and number of animals in clofibrate as well as saline pretreated, isoprenaline challenged rats have been depicted in [Fig.1]. As the data obtained do not conform to a normal distribution curve, Fisher's exact probability test was applied.[17] Grades of myocardial necrosis were divided into two groups arbitrarily; group A containing O, I and II grades and group B, III and IV grades. Number of animals in group A and B of clofibrate treated rats were then compared with saline receiving rats. Clofibrate provided significant (p < 0.05) protection from development of myocardial necrosis.
B. Effect of pretreatment with clofibrate on euglobidin clot lysis time (ECLT) and plasma fibrinogen (PF) in normal as well as isoprenaline challenged rats:
The results obtained have been summarized in [Table 1]. Clofibrate per se did not produce any significant alteration in ECLT or PF. Isoprenaline challenge produced marked (p < 0.001) rise in ECLT' and PF while pretreatment with clofibrate in such animals partially prevented this increase in ECLT and PF significantly (p <0.001 and <0.001 respectively) .

  ::   Discussion Top

Effect of clofibrate on fibrinolytic activity has been a matter of dispute.[3], [5], [18] In the present study, however, clofibrate per se did not exhibit any significant effect on fibrinolytic system as ECLT and PF remained unaltered [Table 1]. These findings are in agreement with those of Sweet et al.[18] Concomitant with myocardial necrosis, the massive doses of isoprenaline exhibited significant diminution in PFA (as evidenced by prolonged ECLT) and rise in PF levels [Table 1]. Interestingly clofibrate pretreatment afforded only partial protection (p < 0.05) to myocardium against isoprenaline induced necrosis. However, Wexler and Greenberg[20] failed to observe histological improvement in cardiac necrosis following isoprenaline challenge.
Results of the present study explicitly indicate that clofibrate significantly prevented the decrease in PFA and increase in PF levels which are inevitable consequences of myocardial infarction.[4], [16] Depression in fibrinolytic activity following myocardial infarction could in part be attributed to the antifibrinolytic property of lipids8 which are known to be raised following myocardial infarction.[11] Antilipaemic action of clofibrate could account for the prevention of the diminution in PFA. Registered improvement in PFA during acute stress of myocardial infarction in clofibrate treated animals, might as well be contributed by the steroids9 which are increased by clofibrate.[20] Since depression of PFA and elevation of PF are the responses of acute myocardial infarction4, [16] and clofibrate is devoid of a per se effect on fibrinolytic system, it will not be unfair to speculate that prevention of changes in PFA and PF are secondary to protection of myocardium from isoprenaline induced damage.
In view of the favourable effects of clofibrate on myocardial necrosis, abnormal PFA and PF, further clinical studies are required to re-evaluate its utility in cardiovascular disorders.

  ::   References Top

1.Bucked, M.: The effect of citrate on euglobulin methods of estimating fibrinolytic activity. J. Clin. Path., 11: 403-405, 1958.  Back to cited text no. 1    
2.Carlson. L. A., Danielson, M., Ekberg, t.. Klintemer, B. and Rosenhamer, G.: Reduction of myocardial infarction by the combined treatment with clofibrate and nicotinic acid. Atherosclerosis, 28: 81-86, 1977.  Back to cited text no. 2    
3.Chakrabarti, R . , Fearnley, G. R. argil Evans, J. F.: Effect of clofibrate on fibrinolysis, platelet stickiness, plasma fibrinogen and serum cholesterol. Lancet, ii: 1007-1009, 1968.  Back to cited text no. 3    
4.Chakrabarti, R . , Hocking, E. D. and Fearnley, G. R.: Reaction pattern to three stresses-electroplexy, surgery and myocardial infarction-of fibrinolysis and plasma fibrinogen. J. Clin. Path., 22: 659-662, 1969.  Back to cited text no. 4    
5.Cotton, R. C. and Wade, E. C.: Clofibrate and the fibrinolysic system. Lancet, is 263-264, 1964.  Back to cited text no. 5    
6.Cucinotta, D., Ferretti, P. G., Dacco, L. and Mazzera, F.: The clofibrate-dipyridamol combination in the prevention and therapy of arteriosclerotic vascular disease and its complication. Geriat. Clin. Med., 58: 475-486, 1977.  Back to cited text no. 6    
7.Dewar, H. A. and Oliver, M. F.: Secondary prevention trials using clofibrate: A joint commentry on the New Castle and Scotish trials. Brit. Med. J., 4: 784-786, 1971.  Back to cited text no. 7    
8.Dubber, A. H. C., Rifkind, B. M., Gale, M., McNicol, G. P. and Douglas, A. S.: The effect of fat feeding on fibrinolysis, `stypven' time and platelet aggregation. J. Atheroscler. Res., 7: .225-232, 1967.  Back to cited text no. 8    
9.Fearnley, G. R.: Fibrinolysis, In: "Advances in Drug Research," Vol. 7, Eds. Harper, N. J. and Simmonds, A. B., Academic Press, London, 1970, p. 148.  Back to cited text no. 9    
10.Krasno, L. R. and Kidava, G. J.: Clofibrate in coronary heart disease-Effect on morbidity and mortality. J. Amer. Med. Assoc., 219: 845-851, 1972.  Back to cited text no. 10    
11.Oliver, M. F., Kurien, V. A. and Greenwood, T. W.: Relation between serum free fatty acid and arrhythmias and death after acute myocardial infarction. Lancet, is 710-715, 1968.  Back to cited text no. 11    
12.Rona, G., Chappel, C. 1., Balazs, T. and Caudry, R.: An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. A.M.A. Arch. Path., 67: 443-455, 1959.  Back to cited text no. 12    
13.Saxena, K. K., Gupta, B., Kulshrestha, V. K. and Prasad, D. N.: An experimental investigation to correlate changes in plasma fibrinolytic activity with isoprenaline induced myocardial damage. J. Postgrad. Med., 25: 147-153, 1979.  Back to cited text no. 13    
14.Saxena, K. K., Gupta, B., Srivastava, V. K., Kulshrestha, V. K. and Prasad, D. N.: On the significance of plasma fibrinogen level to assess the severity of myocardial damage-an experimental study. Ind. J. Expt. Biol., 17: 600-602, 1979.  Back to cited text no. 14    
15.Saxena, K. K., Srivastava, R. K., Kulshrestha, V. K. and Prasad, D. N.: A simple gravitnetric method for estimation of plasma fibrinogen. Ind. J. Physiol. & Pharmacol., 23: 137-139, 1979.  Back to cited text no. 15    
16.Saxena, K. K., Srivastava, R. K. and Prasad, D. N.: Myocardial damage vis-a-vis plasma fibrinolysic activity and fibrinogen level-an experimental study. Ind. .I. Med. Res., 70: 263-267, 1979.  Back to cited text no. 16    
17.Siegal, S.: "Nonparametric Statistics for the Behavioural Sciences", McGraw Hill Book Co. Inc., New York, 1956, p. 96.  Back to cited text no. 17    
18.Sweet, B., Rifkind, B. N., and McNicol, G. P.: The effect of Atromid-S on the fibrinolysic enzyme system J. Atheroscler. Res., 5: 347-350, 1965.  Back to cited text no. 18    
19.The Coronary Drug Project Research Group; Clofibrate and niacin in coronary heart disease, J. Amer. Med. Assoc., 231: 360-381, 1975.  Back to cited text no. 19    
20.Wexler, B. C. and Greenberg, B. P.: Protective effects of clofibrate on isoproterenol induced myocardial infarction in atherosclerotic and nonatherosclerotic rats, Atherosclerosis, 29: 373-395, 1978.  Back to cited text no. 20    

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Online since 12th February '04
2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
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