DISORDERED

“FIBRINOLYTIC

CORONARY I .D. Walker;

POTENTlAL”

IN

HEART DISEASE.

J .F. Davidson;

I. Hutton

and T .D .V.

Lawrie.

Department of Haematoiogy and University Department Glasgow Royal Infirmary. of Medical Cardiology, Scot la rut. Glasgow,

(Received 23.7.1976; in revi.sed form l.3.12.1976. Accepted by Editor A.S. Todd. Received by Executive Editorial Office 28.1.1977) ABSTRACT 25 male patients with and 14 male controls without, angiographic evidence of coromry heart disease were each subjected to a 5 minute venous occlusion test of “fibrinolytic potential”. 13 of the patients had evidence of disordered “fibrinolytic potential” whilst all of the controls were normal. It is concluded that disordered “fibrinolytic potential” may be associated with coronary heart disease and it is suggested that disordered fibrinolysis should be corrsidered as a possible “risk factor” in the development of coror~~ry heart disease.

INTRODUCTION. The aetiology of atherosclerotic coronary heart disease is imperfectly understood, but it would appear to be multifactorial and the identification and evaluation of possible “risk factors” which are associated with the development of vascular disease continues. Rokitansky (1) first associated atherosclerosis with excessive fibrin deposition in the arterial intima and recently this thrombogenic theory of atherosclerosis has been reIt is postulated that normally in vivo an equilibrium exists between examined (2, 3). coagulation and fibrinolysis so that there is a balance between the deposition and t&set of this balance, by, for example a defect in the dissolution of fibrin (4). fibrinolytic system could permit continuous vascular fibrin deposition and consequently a predisposition to thrombosis and eventua I ly to atherosclerosis. The fibrinalytic activity of plasrw is largely due to the presence in the plasma Resting levels of of a labile protein the so-called vascular plasminogen activator. this activator are often low so that their measurement may yield conflicting results which Release of this fibrinolytic do not readily permit inter-individual comparisons. activator is enhanced by a number of different stimuli including, pyrogens, adremline, 509

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"FIBRINOLYTICPOTENTIAL"

nicotinic acid or other vasoactive agents and physical or emotioml

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stress. (5, 6, 7, 8,

9). Marked increases in local fibrinolytic activity also normally occur during venous occlusion of a limb. (TO, 11, 12). and this phenomenon has formed the basis of a number Providing the conditions are rigidly standardised, 20 minutes of clinically useful tests. venous occlusion can be used to assess “fibrinolytic capacity” (13) but 20 minutes venous occlusion is painful and appears to cause significant depletion of the endothelial stores A more convenient and acceptable test is the 5 minute venous of vascular aativator. cuff “fibrinolytic potential” which is less painful and can be repeated at short intervals (14). Recent studies have demonstrated an increased incidence of defective fibrinolytic response to venous occlusion in subjects with recurrent venous thrombosis (l5) and it is well documented that the South African Bantu, in whom coromry atherosclerosis is extremely tore, have much greater spontaneous fibrinolytic activity than their white counterparts in whom coromry artery disease is relatively common (l6, 17). In the study reported here, patients with coromry angiographic evidence of coronary heart disease have been studied, and the incidence of disordered “fibrimlytic potential” in a group of 25 such patients recorded.

PATIENTS

AND

METHODS.

Patients: 25 male patients (mean age 46 years) with angiogmphic evidence of occlusive coronary arterial disease and 14 male controls (mean age 45 years) with normal coronary All 25 patients had angina pectoris and 16 vessels on angiogmphy have been studied. of them had E .C .G. evidence of previous myocardial infarction. Nine of the 14 controls were men with a history of chest pain admitted to exclude commry heart disease. The remaining 5 controls had evidence of valvular disease of the heart and had diagnostic cardiac catheterisation with viswlisation of the coronary arteries by aortogmphy. Patients with peripheml vascular disease or a history of venous thrombosis were excluded and no one with diabetes mellitus or known or suspected neoplastic disease was examined. Special care was taken to exclude subjects who had been taking 13 adrenergic receptor blocking agents during the preceding 6 months and no one who had had any kind of invasive procedure in the month before admission was studied. Details of each subjects past (within 5 years) and present smoking habit were recorded. Patients and controls were admitted to the ward 24 -48 hours before entering the study and angiogmphy was not performed until after the last venous occlusion test had been aarried out. All 25 patients and the 9 controls with chest pain had Commry Artery Visualisation: coronary angiogmphy carried out using either the Judkin’s (l8) cr the Sane’s (l9) Left ventriculogmphy was performed and views of the right coromry artery technique. were obtained in the left anterior oblique, the left lateml and the right anterior oblique positions. Views of the left coronary artery were obtained in these positions and in’the posterior anterior position. The 6 controls with valvular disease of the heart had left heart catheterisations performed using a percutaneous technique with the femoml artery as the site of entry. Biplane cineangiogmphic views were obtained in the right anterior oblique and the left Jateml positions at aortogmphy thus allowing viswlisation

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"FIBRINOLYTICPOTENTIAL"

of both right and left coromry arteries. 5 minute venous occlusion “fibrinolytic potential”: A standardbed 5 minute venous occlusion test has been developed to assess “fibrinolytic potential”. Resting spontaneous fibrinolytic activity is measured in blood collected from the right antecubital fossa and compared with the activity in blood collected from the left antecubital fossa after precisely 5 minutes venous occlusion of the left upper arm. Fibrinolytic activity is measured in euglobulin precipitates prepared from the plasma samples using a meticulous cold technique and adjusting the pH of the plasm0 dilutions to 5.9 (20). The assays were performed in triplicate on unheated plasminogen rich bovine fibrin plates and the product of two perpendicular diameters of the lysed areas arbitmrily expressed as the “area of lysis - in rnd#I. The methodology for this has been described in detail in a previous publication (14). On all subjects a total of three 5 minute venous occlusion testsweredone-atOhours(9am-Doyl),at5hounQpm-Dayl)andat72hours (9 am - Day 4). The subjects were resting supine during the tests and for at least 20 minutes prior to each test. They had been fasting for 12 hours before the tests at 0 hours and 72 hours but had had a light lunch 2 hours before the 5 hour test. Fasting Lipoprotein Status: Samples for measuring the fasting lipoprotein status were taken from the subjects immediately before the 0 hour venous occlusion test and after the subjects had been fasting for 12 hours. Total plasma cholesterol was measured using the method described by Annon (21) and a fluorometric assay of the triglycerides @2) was also done on each subjects plasma. In addition many of the subjects fasting plasmas underwent full lipoprotein fmctiomtion (23) by ultmcentrifugation and precipitation. The mnges used in assessing the results were the age related upper limits of normality described by Fredrickson 04).

RESULTS . Spontaneous Resting Fibrinolytic Activity: The mnges of fibrinolytic activity in samples taken from the resting subjects’ right (unoccluded)arms at 0 hours, 5 hours and 72 hours along with the means of these values are recorded in Table 1 . These mnges were very wide, especially in the patient group. There were no significant differences at the P (0.01 level between the patient and control means at any test time, but at 5 hours the control mean was significantly greater than the patient mean at the P 4 0.025 level. This significant difference is probably due to a reduction of fibrinolytic diurnal variation in the patient group. Two of the patients had no spontaneous fibrinolytic activity on any of the three occasions on which they were tested. One patient had no activity at 0 hours, and very low levels at 5 hours and 72 hours. All of the controls had evidence of spontaneous fibrinolytic activity every time they were tested but again the range of activity noted at each time was wide. The ranges of fibrinolytic activity in the samples Post Occlusion Fibrinolytic Activity: taken from the subjects’ left arms after 5 minutes venous occlusion along with the means of these values are recorded in Table 2. At 0 hours and at 72 hours, that is in the two tesk carried out at 9 am, no significant differences were observed in the mean post-occlusion activities in the patient group

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TABLE

0 hours Patients

tNumber Range (mm2) Mean (mm2) S.D. (mn$) S.E. (mm )

t value P value

I

1.

5 hours

I

Controls

Patienk

Controls

13 81-323 147 70 19

24 O-406 185 94 19

13 156-325 238 51 14

25 G355 116 77 15 1.277 LO.15

,

Disordered "fibrinolytic potential" in coronary heart disease.

DISORDERED “FIBRINOLYTIC CORONARY I .D. Walker; POTENTlAL” IN HEART DISEASE. J .F. Davidson; I. Hutton and T .D .V. Lawrie. Department of Ha...
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