Effect of lipids on thrombocyte aggregation in patients with ischemic heart disease

Platelet lipid composition was studied in healthy subjects and patients with coronary heart disease (CHD) and effects of various phospholipids (PL) were examined on aggregatory parameters. The patients with CHD was found to show higher levels of lysophosphatidylcholine (LPC), phosphatidic acid (PA), cholesterol (Chol), increased Chol/PL of saturated fatty acids, elevated malonic dialdehyde and lower phosphatidylinositol (PI) concentrations. Addition of liposomes from various PL classes to platelet-rich plasma indicated as follows. Phosphatidylserine (PS) liposomes caused a decrease in the platelet aggregation both in healthy subjects and CHD patients. Phosphatidylcholine- (PC), phosphatidylethanolamine- (PE), PI-, and LPC-liposomes increased the platelet aggregation in healthy subjects. Incubation of PE- and PI-liposomes with platelet-rich plasma from CHD patients resulted in lower platelet aggregation, whereas that of PC and LPC liposomes led to its increase. In CHD patients, the changes in the platelet lipid composition were likely to occur due to stimulation of lipid peroxidation and activation of platelet phospholipases, and diminished platelet aggregation caused by addition of PI- and PE-liposomes was likely to be associated with reconstruction of lipid composition and reduction of substrates of the phosphoinositide cycle.     

Effect of naftidrofuryl on viscoelasticity, thrombocyte aggregation and erythrocyte fluidity of blood]

In 30 patients suffering from cerebrovascular disease stage I with atherosclerotic plaques in the carotid's bifurcation the effect of a 7-days application with 400 mg Naftidrofuryl versus NaCl was tested. As parameters viscosity and elasticity of whole blood, plasma viscosity, erythrocytes' and membrane fluidity point, as well as platelet aggregation (spontaneous, ADP-, Epinephrine- and Collagen-induced) were determined before onset, after 4 days and after 8 days. After 8 days treatment with naftidrofuryl there was a significant improvement in viscosity and elasticity of whole blood as well as in erythrocytes' elongation, membrane-fluidity and in the induced test of platelet aggregation.     

New thrombocyte aggregation inhibitor in therapy of unstable angina

Unstable angina is a critical phase of coronary heart disease with a risk for myocardial infarction or death of up to 20% within 30 days. Glycoprotein IIb/IIIa antagonists are a new class of potent antiplatelet drugs. In several large randomized trials, it has been well established that the antibody abciximab, and the low molecular synthetic compounds tirofiban and eptifibatide, reduce the cardiac event rate by 10 to 70% in patients with and without percutaneous interventions. This effect was found to be predominately present in patients with elevated troponins. Accordingly, glycoprotein IIb/IIIa antagonists represent a major achievement for the treatment regimen of patients with unstable angina.     

Platelet membranes and thrombocyte aggregation in rats with spontaneous hypertension

Calcium binding was significantly reduced, and lipid microviscosity increased, in platelet membranes and erythrocyte shadows of spontaneously hypertensive rats (SHR). Their platelet sensitivity to calcium was already increased at the prehypertensive stage, and the rate of A23187-induced platelet aggregation was increased significantly by 24 weeks of life. The demonstrated biochemical properties of SHR's platelet membranes can account for their increased aggregative capacity and may be important in the pathogenesis of arterial hypertension.     

Zebrafish thrombocyte aggregation by whole blood aggregometry and flow cytometry

Zebrafish has become an excellent model system to study mammalian hemostasis. Despite our extensive efforts to develop technologies to measure zebrafish hemostasis and even with previously established thrombocyte qualitative and quantitative functional assays, quantifying thrombocyte function for high throughput applications has been a challenge. In this paper, we have developed two quantitative methods to estimate thrombocyte aggregation: one by whole blood aggregometry and the other by flow cytometry. We found that it is possible to conduct whole blood aggregometry using only 2?µl of blood and the currently available aggregometer. Each of three agonists, arachidonic acid, ADP, and collagen yielded impedance curves similar to those obtained with human blood. We were also able to use flow cytometry to indirectly quantify the extent of thrombocyte aggregation by labeling whole blood with mepacrine, aggregating in the presence of each of the above agonists, separating the aggregates from the white blood cells by centrifugation, and then sorting the resulting white cell fraction for thrombocyte numbers. These methods have high throughput capabilities and have the potential to be used in large scale screens to detect and characterize mutants with thrombocyte functional defects or to identify genes involved in thrombocyte function by large scale knockdowns.