Hideo Ikarugi

High intensity exercise enhances platelet reactivity to shear stress and coagulation during and after exercise

Platelets play a crucial role in the pathogenesis of acute cardiac events, such as angina, myocardial infarction and sudden death. It is believed that regular low-intensity exercise can reduce, while high-intensity exercise may provoke acute cardiac events. The aim of the present study was to investigate the effect of acute exercise both at low and high intensities on the ventilatory threshold (VT), platelet reactivity and coagulation before and after exercise. Platelet reactivity and coagulation were measured under flow condition, using native blood, by hemostatometry. Seven healthy young men (age: 20–29 years) performed bicycle ergometer exercise for 30 min at intensities of 90% (Ex-VT90% or approximately 55% VO2max) and 130% (Ex-VT130% or 80% VO2max) of individual VT. Blood cell counts, hematocrit, blood lactic acid and plasma catecholamine levels were slightly but significantly increased after Ex-VT90% and markedly after Ex-VT130% after 30 min exercise. Subsequent to the exercise, the elevated blood cell counts decreased to the resting levels both at Ex-VT90% and at Ex-VT130%. Platelet reactivity to shear stress and dynamic coagulation were significantly enhanced immediately and 30 min after Ex-130%VT. In contrast, no significant changes occurred in those of Ex-90%VT. The present study suggests that high-intensity exercise-induced platelet hyperreactivity and hypercoagulable state may pose an increased risk for acute, sometimes fatal cardiac event. On the other hand, our findings support the view that low-intensity exercise does not present a risk of thrombosis.

Impaired spontaneous thrombolytic activity in elderly and in habitual smokers, as measured by a new global thrombosis test.

We used a new test (the Görög Thrombosis Test) for assessing the effect of aging, smoking and exercise habits on the overall thrombotic status including platelet reactivity and spontaneous thrombolytic activity of 30 healthy young males (mean, 21.1 ± 0.4 years) and 34 elderly males (64.5 ± 1.1 years). The occlusion time (OT) and the lysis time (LT) were measured from a single native blood sample. The OT is an index of platelet activation and subsequent occlusive thrombus formation by high shear stress, while the LT is an index of the resumption of blood flow due to thrombolysis. The LTs in the elderly group were significantly longer than in the young group (P < 0.001). The LTs of elderly smokers were significantly longer than those of non-smokers (P < 0.001). Exercise did not affect the LT significantly. Platelet reactivity to shear stress (OT) was not affected either by aging, smoking or exercise habits. Suppressed spontaneous thrombolytic activity in elderly males and smokers could be a mechanism of acute thrombotic events in these people.

First direct comparison of platelet reactivity and thrombolytic status between Japanese and Western volunteers: Possible relationship to the “Japanese paradox”

OBJECTIVE To determine and compare thrombotic and endogenous thrombolytic status in Japanese and Western populations. BACKGROUND Incidence of coronary heart disease (CHD) and AMI in Japan remains lower than in Western countries. Primary genetic effects are unlikely, given the increased CHD in Japanese migrants. For men, cholesterol and blood pressure have been similar in Japan and the U.S. Dietary factors are implicated, but how these effect CHD is unclear. We postulated that differences in thrombotic and/or thrombolytic status may contribute. METHODS We measured thrombotic and thrombolytic status in 100 healthy Japanese (J) from Japan and 100 healthy Westerners (W) from the U.K. using the Global Thrombosis Test (GTT). The GTT employs non-anticoagulated blood to create platelet-rich thrombi under high shear (occlusion time OT; seconds), and then measures the restart of blood flow, due to spontaneous thrombolysis (lysis time LT; seconds). RESULTS OT was longer in (J) compared to (W) (545 vs. 364, p<0.0001). LT was longer in (J) than in (W) (1753 vs. 1052, p<0.0001). Distribution of LT in (J) did not conform to a normal population, with markedly impaired thrombolytic status (LT>3,000 s) in 18%, compared to none of the Westerners (p<0.0001). CONCLUSIONS There are marked differences in thrombotic and thrombolytic status, with (J) having less prothrombotic (longer OT) but less favourable endogenous thrombolytic profile (longer LT). This may be important in the aetiology of thrombotic events. Since platelets and thrombolysis were both inhibited in (J) and yet incidence of AMI is lower, OT would seem more important than LT as a determinant of overall thrombotic risk in this population.

Detection of a prothrombotic state after acute aerobic exercise

Angina, myocardial infarction, and sudden cardiac death are associated with thrombus formation in coronary arteries. It is generally believed that these conditions benefit from long-term exercise. However, the evidence for such amelioration or prevention is inconclusive and so is the mechanism through which long-term exercise exerts its beneficial effect on various ischaemic conditions. Because of the thrombotic events, the effects of exercise on platelet reactivity, blood coagulation and fibrinolysis have been extensively studied, but the findings are not consistent (1-9). This is mainly due to methodological problems. Analysis of platelet response to a variety of agonists and the dozen of coagulation and fibrinolysis variables makes the assessment of the overall platelet function, coagulation and fibrinolysis status extremely difficult.

Antithrombotic effect of taurine in healthy Japanese people may be related to an increased endogenous thrombolytic activity

INTRODUCTION Prevention of arterial thrombotic diseases has high priority in developed countries. Taurine (2-aminomethylsulfonic acid), which is rich in sea foods, showed antithrombotic effect in animal models of thrombosis. The present study aimed to investigate such effect in healthy human volunteers. METHODS AND RESULTS In 101 healthy Japanese people the overall thrombotic status was accessed from non-anticoagulated blood sample by the Global Thrombosis Test (GTT). There was no significant correlation between taurine concentration in urine samples and GTT-Occlusion Times (OT; mainly reactivity of platelets). In contrast, a significant inverse correlation was demonstrated between urine taurine concentrations and GTT-Lysis Times (LT; showing spontaneous thrombolytic activity). CONCLUSIONS Our findings suggest that taurine enhances endogenous thrombolytic activity which could be a mechanism of the earlier observed cardioprotective and antithrombotic effect.

Mechanism of the Antithrombotic Effect of Dietary Diacylglycerol in Atherogenic Mice

Introduction: We have shown earlier that diacylglycerol (DAG) but not triacylglycerol (TAG) inhibited thrombus formation. The aim of the present study was to investigate the mechanism of this antithrombotic effect of DAG. Materials and Methods: Four different diets, the (1) Western-style high-fat diet (HFD) containing 20% lipid and 0.05% cholesterol (w/w), (2) TAG-rich and (3) DAG-rich HFDs containing 20% lipid and 0.05% cholesterol, but all lipid replaced by TAG or DAG oil with very similar fatty acid composition and the (4) Japanese-style low-fat diet (LFD) containing 7% oil but no cholesterol were given to apolipoprotein E and low-density lipoprotein (LDL) receptor double-deficient mice. Atherogenicity was assessed by morphology, mapping the whole aorta and measuring the total area of lipid-stained lesions. Endothelial function was measured by the flow-mediated vasodilation test. Platelet reactivity was assessed from native blood sample by a shear-induced platelet function test (hemostatometry). Serum lipoprotein profile was measured by HPLC. Results: Both the Western-style and the TAG-rich HFDs have accelerated atherosclerosis. In contrast, DAG-rich HFD inhibited the atherosclerotic process to an extent comparable with the Japanese-style LFD. There was no significant difference in platelet and coagulant activity between the studied diet groups. DAG-rich but not the TAG-rich HFD significantly suppressed serum LDL cholesterol level. Conclusions: The present findings suggest that the mechanism of antithrombotic and anti-atherogenic effect of DAG may involve the protection of the vascular endothelium from injury and lowered serum LDL cholesterol.

The exercise paradox may be solved by measuring the overall thrombotic state using native blood

While exercise is widely believed to prevent atherothrombotic diseases, it occasionally causes sudden death. This exercise paradox may be due to the inadequate testing of the thrombotic and thrombolytic status. A recently developed shear-induced thrombosis/endogenous fibrinolysis test performed with non-anticoagulated blood samples allows the assessment of the thrombotic state of an individual both at rest and after exercise. This sensitive and physiologically relevant test may help to solve the aforementioned exercise paradox.

Prevention of thrombotic disorders by antithrombotic diet and exercise: evidence by using global thrombosis tests

Prevention of thrombotic disorders has priority over treatment. There are only two pathologically relevant tests which are suitable for measuring the overall thrombotic status both in experimental conditions and in humans. The Global Thrombosis Test (GTT) and the Global Parallel-Plate Thrombosis Test can detect the pathologically relevant global thrombotic status. These tests have been successfully used for monitoring the effect of antithrombotic drugs and for developing novel antithrombotic agents. By using GTT, varieties of fruits, vegetables, and regular physical exercise have been tested for the effect on global thrombotic status. This review discusses the published evidence for the benefit of diet of selected fruit and vegetable varieties and doing regular physical exercise on improving thrombotic status. Future clinical trials monitored by GTT or Global Parallel-Plate Thrombosis Test could decide on the effectiveness of an experimentally proven antithrombotic diet with regular physical exercise in the prevention of thrombotic diseases.