Changes in Blood Coagulation and Fibrinolysis in Rats Fed Atherogenic Diets

Abstract

Summary1. Groups of rats were fed thrombogenic diets and the effects on blood coagulation and fibrinolysis assessed.2. Animals fed a diet containing cholesterol, thiouracil and cholic acid developed high levels of coagulation factors I, II, V, VII—X, VIII, IX and X.3. Animals fed a similar diet with additional 40% beef fat developed even greater elevation of V, VII—X, VIII and X, similar elevation of factor II, and lesser (but still significant) elevation of factors I and IX. In addition marked elevation of blood platelets occurred.4. Euglobulin lysis time of the group not fed the additional fat was longer than in controls. Significant prolongation of euglobulin lysis time was not found in the group fed additional fat.5. If the increased levels of plasma fibrinogen were taken into account, it was found that a larger amount of fibrin was lysed per unit time in the euglobulin lysis test with plasma from rats fed either atherogenic diet compared with controls.6. Defective thromboplastin generation was present in both groups of rats fed an atherogenic diet. The defect was present in the serum and was not due to lack of a factor required for thromboplastin generation. An inhibitor was present in the serum which was capable of preventing the action of normal serum.7. No good correlation was found between the occurrence of changes in blood coagulation or fibrinolysis and the presence or absence of thrombosis and infarction.8. The exact cause of these anomalies remains unexplained, as does the cause of the thrombosis in these animals. Starvation per se does not account for these abnormal findings. They could not adequately be explained on the basis of “hypercoagulability” of the blood.

Increased Plasma Fibrinogen and Platelet-Aggregates in Type II Hyperlipoproteinaemia

“…While there is little doubt that subjects with Type II hyperlipoproteinaemia develop premature arterial disease (Lees and Wilson 1971), the mechanisms are not known, and there is as yet no definite evidence that reduction of plasma lipids by diet or drugs reduces this risk. We have shown that such patients have increased levels of plasma fibrinogen and platelet-aggregates, both of which can be induced in experimental animals by high cholesterol diets (Merskey andWohl 1964, Wu et al 1975). These abnormalities may play a part in the pathogenesis of atherosclerosis or arterial thrombosis.…”

“…Elevated levels of plasma fibrinogen are also associated with coronary artery disease (McDonald and Edgill 1957). Animals fed high-cholesterol diets to produce experimental atheroma develop high levels of plasma fibrinogen (Merskey and Wohl 1964) and platelet-aggregates (Wu et al 1975) measured by the technique of Wu and Hoak (1974). We compared levels of plasma fibrinogen and platelet-aggregates in patients with Type II hyperlipoproteinaemia and in matched controls.…”

Dietary Fats and Arterial Thrombosis

“…When fed to rats for 3-4 months, it produces thrombosis in about 50 % of the animals, whereas myocardial infarction is observed in about 25 %. As reviewed by H o w a r d and G resham [60], this type of diet produces hypercoagulability [81], hyperlipidemia and hyperlipoproteinemia [61], it does not affect platelet stickiness, but in creases the platelet count. The type of fat determines the thrombogenicity of the diet: butter, lard, hydrogenated coconut oil, cocoa butter, hydro genated groundnut oil and maize oil being thrombogenic, groundnut oil being nonthrombogenic.…”

Essentielle Hyperlipämie und verminderte Fibrinolyse-Aktivität

“…H owell (13) berichtete über eine Hemmung der Fibrinolyse. Zahlreiche Autoren prüften die Fibrinolyse unter Fettbelastung und kamen zu divergierenden Ergebnissen: G reig (11), J ames et al (14), M erskey et al (18) so wie H owell (13) beobachteten eine Hemmung, N itzberg et al (19), Fearnley (8) und R asmussen et al (22) (25) erfolgte die Blutentnahme stets morgens etwa 16 Stunden nach der letzten Nahrungsaufnahme. Blut wurde aus der Vena cubitalis gewonnen, in heparinisierten Zentrifugenröhrchen aus Plastik aufgefangen und sofort nach der Abnahme bei 3000 rpm und 4°C 10 Minuten lang zentrifugiert.…”