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Hemorheological Changes in Senile Cerebro-vascular Conditions and Its Inter


 

By Liao Fulong  Institute of Chinese Materia Medica, China Academy of Traditional Chinese Medicine, Beijing 100700)

The pioneer of biorheology, A. L. Copley, pointed out that hemorheology is a science dealing with flow and deformation of blood and blood vessels at macroscopic, cellular and even molecular levels. Copley described blood and blood vessels as ''vessel-blood organ". Therefore, hemorheological investigation on senile cerebrovascular conditions should include the above mentioned aspects and their interactions.

Hemorheological studies show that blood rheological parameters have a tendency of increase with-aging, such as hemaiocrit, fibrinogen level and plasma viscosity. As blood viscosity is concerned, the reports show a pattern of diversity. However, hemorheological impairments are common at pre-senile or senile stages.

Clotting rheology is interested in plasma coagulation factors and their rheological behavior. Determinations on V: C, V?: C, V? R: Ag and fibrinogen show that hypercoagulation exists in the elderly. Studies show that the tendency of thrombosis is significantly enhanced due to platelet hyperactivity. Platelet intracellular calcium, membrane P-selectin and release of ß-TG are all increased with aging. Platelet aggregation and thrombus formation tests show marked elevations in the elderly.

Vascular degenerative changes with aging are indicated by stiffness of vessel wall and an increase in micro-vascular systolic pressure. CT data of 298 cases of normal elderly showed 164 cases of calcification at intracranial segment of internal carotid, including 82 cases of transit ischemic attack, 20 cases of thrombosis and 2 cases of hemorrhage late on. Ultrasonic Doppler investigation on 188 cases of senile cerebrovascular diseases showed that sclerosis of extracranial internal carotid is a risk factor for cerebrovascular ischemic diseases.

Cerebro-thrombosis appears to be the highest incidence in cerebrovascular diseases. Plasma fibrinogen is elevated during the acute phase of cerebrothrombosis. Increase in platelet P-selectin and decrease in membrane fluidity of red and white cells are reported.

The above mentioned changes in hemorheology indicates that a tendency of hyperviscosity, hypercoagulation and being prone to thrombosis is characteristic in normal elderly. The pathological development will be a matter of interactions between blood, blood flow and blood vessel under abnormal conditions. Susceptibility to atherosclerosis and stenosis of arteries in the elderly will lead to abnormal high wall shear stress of blood flow. Shear-induced platelet aggregation (SIPA) is likely to happen in cerebrovascular domain due to its high flow volume and velocity. Therefore, to study SIPA in the elderly isreasonable and rneaningful, Plasma vWF, platelet membrane GP Ib, GP Iib/? a and calciurn inflow are all involved in SIPA.

Chinese herbal medicine contributes a great deal to the health of the Chinese nation. Blood stasis syndrome (BSS) is one of the most significant pathological syndromes in traditional Chinese medicine (TCM). The approach of treatment for BSS is activating blood circulation to remove blood stasis (ABCRBS). In 1982, diagnostic criteria for BSS were established by the Committee of ABCRBS. Chinese Association of integration of Traditional Chinese and Western Medicine. It consists of three categories of criteria, namely, the main manifestations, the supplemental manifestations and the laboratory criteria. In fact, since 1980's, using the theory of TCM as a guide coupled with the help of modern science and technology, achievements have been gained in the exploration on the nature of BSS. Many promising reports on clinical practice are found. Microcirculatory and hemorheological abnormalities are recognized as the important laboratory parameters. The parameters are widely employed in the diagnosis of BSS and in the evaluation of efficacy of treatment. In recent years, many of the main diseases have been treated by ABCRBS.

Buyang Huanwu Tang, as a well-known prescription for cerebrovascular disorders, is widely applied clinically. Modern pharmacological studies reveal its effects on improvement in blood viscosity, plasma viscosity, hematocrit and fibrinogen level. Ligustrazine, a compound contained in one herb of Buyang Huanwu Tang, exhibits many beneficial effects. Inhibition of SIPA is attracting attention since it can not be inhibited by aspirin. The effect of ligustrazine on SIPA is investigated by a cone-plate shear device equipped with laser source. Maximum SIPA was determined from the recording of the scattered light. The 50 ok inhibition concentration (IC50 ) of ligustrazine was determined as 0.22, 0.28 and 0.52 mmol/L at shear stress levels of 20 , 40 and 52dyn/cm2 accordingly. The correlation between IC50 and shear stress r follows IC50 = aebr. Laser confocal microscope and calcium probe Fluo-3 and platelet membrane GP Ibantitody were employed to study mechanism of action. Ligustrazine showed significant inhibition on platelet intracellular calcium. Pharznacokinitic study showed the drug could pass the blood-brain barrier. Clinical investigation supports the beneficial inhibition of SIPA by ligustrazine. It appears to be a promising drug for senile cerebrovascular conditions.

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