Prostacyclin synthesis by proliferative aortic smooth muscle cells.
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Biomedical subjects
Publications and source records attributed to H Sinzinger.
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Human lymphatics convert exogenously added 14C-arachidonic acid into PGE2, PGF2 alpha and the main metabolite 6-keto-PGF1 alpha. Thromboxane formation is undetectable either by radiothinlayer-chromatography or by radioimmunology. These data confirm and extend our earlier findings indicating an important PGI2-synthetic mechanism in human lymphatics. Assuming that lymphatic contractility is regulated at least in part by thromboxane A2, we propose that this derivative of arachidonic acid derives from extralymphatic sources.
Platelet labeling with 111-In-oxinesulfate allows visualization of platelet deposition in the vascular bed. Scintigraphic studies were performed in 6 patients with "active" (PUR greater than 1.20) and 8 patients with "inactive" (PUR less than 1.20) atherosclerotic lesions of the femoral artery. Platelet deposition was also studied in 11 patients with implanted prosthetic vascular grafts and in 21 patients with an abnormal aneurysm of the aorta. Infusing 5 ng/kg/min PGI2 during 6 hours for 5 days into patients with "active"-atherosclerosis and aneurysms of the aorta resulted in a significant decrease of platelet deposition even after having stopped the infusion. There was no influence of PGI2 on PUR in patients with "inactive" lesions. The group of patients with implanted prosthetic grafts demonstrated also a significant decrease of PUR values during the PGI2-infusion, but reached baseline values soon after stopping the infusion. When platelet deposition is increased gamma-camera imaging provides valuable date on the influence of any kind of therapy on the in-vivo platelet function.
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The quantitative estimation of luminal diameter of 102 aortas (ascending, thoracic and abdominal aorta) from neonates to adults of 80 years showed a continuous increase with a marked change until the age of 15. From the 20th up to the 80th year we observed a further enlargement of the inner vessel-diameter of about 50%.
In 20 patients with peripheral vascular disease treated with prostacyclin (5 ng/kg/min) we observed a significant activation of platelet function as measured by platelet proteins, ADP-induced aggregation platelet sensitivity and platelet count. Only the platelet survival was significantly prolonged by the treatment.
The possibility of detecting prostaglandins by means of indirect immunoperoxidase-method is reported allowing a differentiation between actual synthesis and inactive metabolites. This technique allows the detection of all important prostaglandins in tissue samples and opens a new route for discovery of prostaglandin synthesis profile of a particular cell type or the electron microscopical localization. Its application in normal and pathological tissue structures will assess the patho-diagnostic value of this new method in the near future.
A method for platelet migration testing is presented. The results are comparable using sodium citrate and acid citrate dextrose as anticoagulants, whereas other anticoagulants lead to lower absolute migration. The day-to-day variability of the method is higher than the intra-day variability. The variability between the patients is higher than that between measurements carried out on the same patient. There is no correlation to ADP-induced platelet aggregation.
Cultured endothelial and smooth muscle cells, as well as vascular tissue samples derived from human coronary arteries and minipig aorta produce thromboxane A2 in trace amounts. The identity of this substance was characterized using a specific thromboxane synthetase inhibitor. Thromboxane (TXB2) was measured by means of specific radioimmunoassay. The biological importance of this phenomenon is unclear.
Earlier investigations revealed morphological damage of the vascular wall after radiotherapy. The present investigation was undertaken to determine whether vascular prostacyclin synthesis plays a causative role in the genesis of vasculopathy. Rabbits were exposed to a focal radiation dose of between 500 and 5000 rad over various time intervals. Vascular PGI2-synthesis increased significantly immediately after radiation, with a subsequent decrease over the following days to levels below the starting values. Each repeated radiation dose induced a significant increase in PGI2-synthesis again. These observations were paralleled by severe morphological alterations, mainly localized in endothelial cells and elastic material. The findings suggest that a deterioration in PGI2-synthesis plays a key role in the genesis of radiation-induced vasculopathy.
It has been reported that low-dose aspirin inhibits prostaglandin synthesis of platelets, but not of endothelial cells. Whereas platelet prostaglandin synthesis is irreversibly inhibited by acetylation of cyclooxygenase, the nuclei-containing vascular wall cells are able to resynthesize this enzyme. The optimal optimal dosage in influencing vascular haemostatic regulation is still an open question in the literature. Hence, we examined the effect of a single dose of aspirin (50-500 mg), given to patients undergoing surgery for varicose veins, on venous wall PGI2 synthesis in a biopsy specimen and on plasma thromboxane B2 levels monitored continuously for up to 96 hours. Our findings demonstrate that a dose as low as 50 mg per day is able to inhibit thromboxane formation significantly. On the other hand, this dose does not influence vascular wall PGI2 synthesis. Based upon these data it is concluded that the optimal dosage to achieve a beneficial effect on haemostatic balance should not exceed 50 mg aspirin per day.
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EPH-gestosis is still today one of the most dangerous complications of pregnancy, threatening both, maternal and fetal life. Until now only symptomatic treatment was possible. A new mode of treatment of EPH-gestosis may evolve from the use of prostacyclin, a potent vasodilator and inhibitor of platelet aggregation. We tried prostacyclin therapy in three patients with severe gestosis. The results of prostacyclin infusion on this condition, the pregnancy, the fetus, the placenta and the morphology of the umbilical artery are discussed.
In 6 months old male Wistar rats 15 mg pentoxifylline/kg body weight were given intravenously in a single dose. The animals were sacrificed after 30, 60, 120 and 240 minutes respectively. It was confirmed that a single pentoxifylline administration enhanced prostacyclin generation by vascular and renal tissue samples, reaching its maximum 60 minutes after the treatment. The time course for PGI2-generation behaves differently in the tissues examined. It is concluded that the drug pentoxifylline might exert its beneficial role in the treatment of peripheral vascular disease at least in part by its influence on hemostatic balance at the endothelial-platelet interaction level.
The diagnosis of secondary or recurrent tumour growth after operations on primary maxillo-facial tumours is still only possible at a late stage. On the other hand, the prostaglandins of the E series assume an important role in connection with tumour growth. The present investigation succeeded for the first time in detecting an increase in the level of 6-oxo-PGF1 alpha, the stable metabolite of PGI2, before planned radical operation in patients with maxillo-facial tumours. In the further course of the illness it was possible to establish a correlation between the plasma values and the occurrence of metastasis or recurrence of disease. These results indicate that a certain significance can be attributed to 6-oxo-PGF1 alpha as a tumour marker.