Prostaglandin E1 decreases activation of arterial smooth-muscle cells.
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Adult↗
Biomedical subjects
H Sinzinger
Publications and source records attributed to H Sinzinger.
Bicyclo-prostaglandin E2 metabolite in congestive heart failure and relation to vasoconstrictor neurohumoral principles.
Vasodilator prostaglandins may play a role in maintaining circulatory homeostasis in patients with congestive heart failure (CHF). Plasma levels of bicyclo-prostaglandin E2 metabolite (PGEm), a chemically stabilized degradation product of the vasodilator prostaglandin E2, were determined in 45 patients with chronic CHF (New York Heart Association class II, III or IV). Mean circulating levels of bicyclo-PGEm were significantly elevated in patients with functional class III (72 +/- 8 pg/ml) or IV CHF (77 +/- 10 pg/ml) compared with control subjects (49 +/- 3 pg/ml) and patients with functional class II CHF (49 +/- 4 pg/ml). Bicyclo-PGEm concentrations correlated with plasma renin activity (r = 0.68, p less than 0.001) and plasma angiotensin II (r = 0.56, p less than 0.001) and plasma noradrenalin levels (r = 0.34, p less than 0.05). An inverse correlation was found between serum sodium concentrations and levels of bicyclo-PGEm (r = 0.46, p less than 0.01) as well as plasma renin activity (r = 0.66, p less than 0.001). Thus, prostaglandin E2 levels in plasma are increased in patients with severe CHF.
Adult↗
[Vasodilating effect of leukotriene C4 and D4 by stimulation of prostacyclin synthesis].
Since the original discovery and structural characterization of leukotrienes, these substances have attracted considerable interest due to their numerous biological activities. It is known that these substances exert a short lasting vasoconstrictory and a longer lasting vasodilatory response. However, the cause of this biphasic response is not clear as yet. Human coronary artery segments synthesize about 50 pg PGI2/cm2/min in vitro under pressure perfusion. At concentrations ranging from 1 to 100 ng leukotrienes C4 and D4 cause a dose-dependent increase in PGI2 generation. Inhibition by acetylsalicylic acid and 15-hydroxyperoxyarachidonic acid indicates the mechanism to be mediated via the cyclooxygenase. It is, therefore, concluded that the capacity of leukotrienes C4 and D4 to stimulate PGI2 formation might play a key role during acute inflammation at the site of white blood cell accumulation.
Coronary Circulation↗
Imaging of human atherosclerotic lesions using 123I-low-density lipoprotein.
In patients suffering from clinically manifest atherosclerosis autologous LDL-labelling has been done using 123I. This technique allows localization of areas with an increased LDL entry as well as a monitoring of kinetics. Normally, no tracer uptake can be seen in the vascular system. Positive camera images, however, can be obtained in pathological areas as early as 60 min after LDL-reinjection. Experimental data and morphological control reveal a very good correlation to the gamma-camera findings. The technique seems to be very promising for diagnosis in patients suffering from atherosclerosis and hyperlipoproteinemia.
Aged↗
Autologous platelet labelling using "Monovette" vials is not septic.
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Blood Platelets↗
Prostacyclin synthesis stimulating plasma factor in patients with primary hyperlipoproteinemia--effect of dietary and drug treatment.
Recent data have demonstrated a possible pathogenetic influence of the prostacyclin synthesis stimulating plasma factor (PF) in various diseases. Studying this PF in 26 patients with primary hyperlipoproteinemia (HLP) we examined patients suffering from types IIa (n = 8), IIb (n = 6) and IV (n = 12) classified according to Fredrickson. Plasma was withdrawn at the detection of the HLP, 4 weeks after a dietary intervention and again 4 weeks after the beginning of a drug treatment. Using various test models such as rat and minipig aortic tissue, human aorta and saphenous vein as well as cultured endothelial and smooth muscle cells, the data reveal an in part significant improvement of PF running parallel with the improvement of HLP. These findings suggest that even though a significant difference between healthy controls and patients suffering from severe atherosclerosis has not been found, there occurs a significant improvement of PF in hyperlipidemic patients after successful treatment. Thus, it can be concluded that normalization of PF is one of the many factors improving the hemostatic balance in patients undergoing beneficial dietary or drug treatment.
Adult↗
Effect of a single pentoxifylline administration on platelet sensitivity, plasma factor activity, plasma-6-oxo-PGF1 alpha and thromboxane B2 in healthy volunteers.
In eight male healthy volunteers aged 25-38 years 300 mg pentoxifylline (Trental, Hoechst AG, Frankfurt/M., Germany) were administered intravenously by a short term infusion for 10 minutes. Blood was withdrawn before as well as 30, 60, 90 and 120 minutes after the infusion. Throughout the entire investigation the volunteers were kept in an upright sitting position in a comfortable chair. Plasma levels of 6-oxo-PGF1 alpha and thromboxane B2 (TXB2), PGI2 release stimulating plasma factor (PF) activity and the platelet sensitivity to PGE and PGI respectively were evaluated at each interval. Plasma levels of 6-oxo-PGF1 alpha exhibited a significant (p less than 0.001) increase in mean values after pentoxifylline administration, reaching the maximum at 60 minutes after infusion. Only a trend (p less than 0.05) was detectable for a decrease in plasma TXB2 values. The PF activity did not change throughout the follow-up period. The platelet sensitivity to PGI2, however, exhibited a significant (p less than 0.01) increase as did sensitivity to PGE1 (p less than 0.005). These results are in accordance with earlier data showing that pentoxifylline is able to increase PGI formation by various tissues. The findings suggest, that the beneficial effects reported for this compound in clinical use might in part be due to its positive effects in local hemostatic regulation.
6-Ketoprostaglandin F1 alpha↗
Influence of type IIa, IIb and IV-hyperlipoproteinemia on platelet prostaglandin sensitivity, plasma thromboxane B2 and platelet half-life.
It is generally accepted that in hyperlipoproteinemia (HLP) the vascular prostacyclin formation is diminished. We wondered, whether HLP is also associated with changes in platelet sensitivity to antiaggregatory prostaglandins. Therefore, we examined the platelet sensitivity to the prostaglandins PGI2 and PGD2 as well as plasma thromboxane B2 (TXB2)-levels in 24 patients with HLP type IIa, IIb and IV. We found a marked decrease of platelet sensitivity to PGI2 in all the patients examined, which was more pronounced in type IIb than in types IIa and IV. Platelet sensitivity to PGD2 showed no difference in the hyperlipemic patients. Plasma TXB2-levels were significantly increased in comparison to a control group, the changes being most pronounced in patients with type IV HLP. Platelet half-life was significantly shortened in the HLP-patients. This in-vivo platelet function parameter was found to be reduced in patients with type IIa HLP to the greatest extent. Our findings suggest that platelet deposition in HLP is promoted not only by diminished vascular PGI2-formation, but also by decreased sensitivity of the platelets to antiaggregatory prostaglandins. The high TXB2-levels and the shortened platelet half-life reflect the in-vivo activated platelet population in these patients.
Adult↗
Prostacyclin formation around human abdominal aortic ostia.
Earlier studies have demonstrated an age dependent effect in the extent of sudanophilic and atherosclerotic lesions around aortic ostia in men. As prostacyclin may be a key determinant in the development of atherosclerosis we examined its formation around abdominal aortic ostia (coeliac, superior mesenteric and inferior mesenteric arteries) in-vitro. Prostacyclin formation was higher distal to the orifice as compared to proximal areas, but without reaching the level of significance. Prostacyclin formation was always higher in females than in males and in nonsmokers than in smokers, showing the greatest difference distal to the ostium, but again without significance. From the limited number of vessels examined, no trend for an age dependency can be noted. The relation between prostacyclin generation and morphological data is discussed.
Adolescent↗
Biological half-life of prostacyclin and 6-oxo-PGF1 alpha levels in plasma of patients with colonic cancer.
Prostaglandins have been shown to play a central role in the formation of cancer. The synthesis of prostacyclin and its bioavailability may be an important local determinant for metastasis. As the amount of the biologically active substance is dependent in part on the half-life (T/2) we examined the question as to whether the T/2 of prostaglandin I2 (PGI2) is altered in patients suffering from colonic cancer at various stages of the disease. In addition, the influence of various therapeutic regimens was investigated. In 58 patients with various stages of colonic cancer no significant difference in PGI2-T/2 could be detected. No significant difference could be found before (10, 11 +/- 1, 9 min) and after (10, 03 +/- 1, 8 min) tumor resection, before (9, 89 +/- 1, 5 min) and after 10, 35 +/- 1,8 min) chemotherapy, before (10, 36 +/- 1, 5 min) and after (10, 89 +/- 2, 31 min) irradiation as well as before (8, 86 +/- 1, 9 min) and after (9, 07 +/- 1, 2 min) tumor resection at least 4 to 6 years ago. In 14 healthy people PGI2-T/2 (10, 05 +/- 2, 1 min) did not differ significantly. In all the 58 patients the plasma levels of 6-oxo-PGF1 alpha, the stable derivative of PGI2 were measured. As compared to healthy controls (less than 1 pg/ml) the actual 6-oxo-PGF1 alpha values of patients with colonic cancer were significantly increased. However, no correlation to the T/2 of PGI2 (r between 0, 03 and 0, 21, n.s.) in plasma in vitro could be discovered. After curative tumor resection and after chemotherapy the plasma levels of 6-oxo-PGF1 alpha were significantly lower than before. The data suggest that in patients suffering from colonic cancer the speed of degradation of PGI2 is not a key determinant in local hemostatic dysregulation favouring early metastasis. However, PGI2 or its stable derivatives may be involved in the development of colonic cancer.
6-Ketoprostaglandin F1 alpha↗
Degradation of prostacyclin in the plasma of patients with terminal liver insufficiency.
It has been suggested earlier that the increased bleeding tendency observed in patients with hepatic coma is due to prostaglandin I2. Various experimental studies have reported an increased prostaglandin I2-formation, an enhanced plasma factor activity and a prolonged synthesis in-vitro. However, the rate of degradation of prostaglandin I2 in plasma could be another determinant alterating the locally available biologically active substance but this has not been examined so far. Thus, we examined the half-life of synthetic prostaglandin I in-vitro in plasma from 25 patients with terminal liver insufficiency in different stages of hepatic coma. In 8 healthy volunteers a 6 months follow up showed no significant change. The half-life of prostaglandin I in controls was 10.21 +/- 2.70 minutes, no different from coma stage I (10.16 +/- 1.36 minutes), coma stage II (10.86 +/- 2.24 minutes), coma stage III (10.95 +/- 3.06 minutes) or coma stage IV (12.07 +/- 2.88 minutes). However, a modest trend towards a prolongation and an increase in standard deviation with the coma stage can be noted. No influence of various drugs commonly used in these patients could be seen. It can thus be concluded that there is no important difference in degradation speed of prostaglandin I2 in the plasma of patients with terminal liver insufficiency, which could account for the increased bleeding tendency.
Adult↗
Prostacyclin synthesis stimulating plasma factor in coronary heart disease.
Evidence has been presented that the prostacyclin synthesis stimulating plasma factor might be altered under various clinical conditions and thereby influence in a positive or negative way the hemostatic balance. Therefore, we studied angiographically verified coronary heart disease patients with a combination of various risk factors. Different test systems like cultured endothelial and smooth muscle cells, rat aorta, human coronary artery, minipig abdominal aorta and aorta of streptozotocin-induced diabetic rat have been used. With an increasing number of risk factors being present, the plasma factor activity shows a trend towards a decrease, however, in none of the groups was the difference statistically significant. It is thus concluded that changes in plasma factor activity are too small to be of clinical importance by influencing hemostatic regulation in humans.
Animals↗
Immunohistochemical detection of 6-oxo-PGF1 alpha and PGE2 in radicular cysts.
Prostaglandin synthesis in the wall of radicular cysts was determined by immunohistochemistry and radiothinlayer chromatography. PGE2 is predominantly produced by plasma cells and histiocytic elements, whereas much less is synthesized by fibroblasts and endothelial cells as estimated using immunohistochemistry. 6-oxo-PGF1 alpha, however, was primarily found to be generated by endothelial cells and fibroblasts; only small amounts seem to be derived from histiocytic elements and plasma cells. The response of the cystic epithelium to anti-PGE2 and anti-6-oxo-PGF1 alpha antibodies was negative or showed only minimal staining. It can thus be concluded that the granulation tissue and its cellular components modulating the inflammatory process are the main source of prostaglandin synthesis in the wall of radicular cysts and may therefore be responsible for the resultant osteolytic activity.
6-Ketoprostaglandin F1 alpha↗
Role of platelets in atherosclerosis.
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Animals↗
Jogging causes a significant increase in platelet sensitivity to prostacyclin.
Platelet function and platelet sensitivity to PGI2 was studied before and after jogging in seven males and four females in good health. The ADP-induced (1 microM) aggregation, being always increased after physical activity, showed during the entire follow-up period of 12 months a significant decrease at rest and after exercise compared with baseline values. The change in the aggregation response was significant for t alpha at month 1 and for delta tmax at month 2 after starting the jogging. The platelet sensitivity to PGI2, being always diminished after exercise, also increased significantly during the entire follow-up period compared with baseline levels. In contrast to the ADP-induced changes, the changes in platelet sensitivity were significant already at week 2. Our findings indicate that daily physical activity causes a significant improvement in platelet function and reduces platelet activation.
Adenosine Diphosphate↗
[Comparison of the renal ultrasound-furosemide test with the isotope nephrogram. Possible clue to the retention phenomenon?].
In 23 patients with essential hypertension renographic and sonographic examination of the kidneys was compared. No correlation could be observed for functional parameters and urinary excretion between the two different methods. Correlations have only been detected between renographic retentions and furosemide-conditioned swelling of the kidneys in sonography: patients with severe retention showed a statistically significant stronger response to furosemide. The increased retention in the renal pelvis could be responsible for alterations in sonographic findings. This study provides new data on the mechanisms of retention, whereby retention in the renal pelvis in some patients seems to be most probably caused by nephrosclerosis.
Adult↗
Inhibition of acetylcholine-induced bronchoconstriction in asthmatics by nifedipine.
The calcium-dependent constriction of bronchial smooth muscle cells and release of mediators derived from mast cells is important in the pathophysiology of asthma. We hypothesized that nifedipine, a slow calcium channel blocker, would inhibit or attenuate acetylcholine-induced bronchoconstriction in asthmatics. Because one consequence of mast cell activation is the release of platelet-activating factor, we wondered whether thromboxane levels would be increased during acute bronchial constriction in asthmatics. Bronchoconstriction was induced in 8 asthmatics (6 men, 2 women) by acetylcholine; each subject was pretreated either with placebo or nifedipine (20 mg sublingually) on 2 separate days. Vital capacity, forced expiratory volume in 1 s, peak expiratory flow rates and oscillatory resistance were measured prior to and after the intake of placebo or nifedipine as well as after an acetylcholine challenge. Pretreatment with nifedipine significantly attenuated acetylcholine-induced changes in all four lung function parameters studied, but did not significantly influence the increase in thromboxane B2 plasma concentrations observed after the acetylcholine challenge. From these data we conclude that nifedipine inhibits the acetylcholine-induced bronchoconstriction in asthmatics. This effect may be either a direct action on bronchial smooth muscle or may be due to the inhibition of mediators other than thromboxane.
Acetylcholine↗