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Biomedical subjects

P Fitscha

Publications and source records attributed to P Fitscha.

At least 55 records · Page 3Linked to original sources
PubMed1990

Prevalence of a shortened prostacyclin half-life in plasma in healthy adults: results of a screening investigation.

Out of a total of 1,981 adults (956 males, 1,025 females; aged 16-71 yr) undergoing a screening investigation for elevated cholesterol only 3 healthy participants with pathologically enhanced prostaglandin 12 (PG12) degradation in plasma in vitro were discovered. The PG12 half-life in these three screenings was shorter than 60 sec and persisted during several follow-up checks. In one patient a familial defect was discovered. Diseases known to be associated with this disturbance in PG12 metabolism have been excluded. The mean half-life of PG12 in 1,978 people amounted to 10.71 +/- 1.93 min. It still needs to be clarified whether this rare disturbance in PG12 metabolism is causally related to, or only associated with, thromboembolic events. A possible predisposition should be elucidated by regular monitoring of affected persons.

Adolescent↗
PubMed1990

Comparison of bopindolol and atenolol in chronic stable angina pectoris.

The efficacy of bopindolol and atenolol in the treatment of patients with chronic stable angina pectoris have been compared in a double blind, randomized study. Both bopindolol 1 mg and atenolol 100 mg for 6 weeks increased mean exercise time (25% and 22%, respectively, compared to placebo), time to angina (27% and 25%), and time to 1 mm of ST-segment depression (32% and 20%). Both drugs reduced ST-segment depression similarly at maximal and submaximal work levels. There was no significant difference in their antianginal efficacy.

Adrenergic beta-Antagonists↗
PubMed1990

Effects of taprostene, a stable prostacyclin analogue, on haemodynamics, platelet function and arachidonate metabolism in healthy volunteers.

In order to assess the effect of taprostene on haemodynamics, platelet function and arachidonate metabolism in 4 healthy volunteers an intravenous infusion of 25 ng.kg-1.min-1 was given for 6 h. During the infusion period systolic blood pressure dropped from 130 to 111 mm Hg and diastolic blood pressure from 77 to 69 mm Hg. The heart rate rose from 77 to 84 beats/min. During the taprostene infusion the slope and height of the ADP and collagen induced platelet aggregation curves were significantly inhibited and the sensitivity of platelets to PGI2 and PGE1 was increased. Plasma and serum thromboxane B2, conversion of exogenous radiolabelled arachidonic acid, WU-test, circulating endothelial cell count, concentration of platelet factor 4, beta-thromboglobulin, malondialdehyde and the PGI2-synthesis stimulating plasma factor did not show any clear drug-related alteration. It is concluded that infusion of taprostene 25 ng.kg-1.min-1 caused measurable inhibition of platelet function ex vivo.

Adult↗
PubMed1990

A double blind placebo controlled trial of intravenous prostacyclin (PGI2) in 108 patients with ischaemic peripheral vascular disease.

108 patients with ischemic peripheral vascular disease were randomly allocated to receive infusion of either PGI2 (6 ng/kg/min over 8 hours daily for 5 consecutive days) or placebo in a double-blind manner. All patients had Stage II disease (Fontaine classification). One month after infusion the absolute and relative walking times were significantly (p less than 0.05) longer in the PGI2- than in the placebo-treated group. Patients were further classified as treatment responders or non-responders on the basis of increase of absolute and relative walking times. After one month 44% (24 out of 54) of the PGI2- and 15% (8 out of 54) of the placebo-treated patients were positive treatment-responders (p less than 0.01).

Clinical Trials as Topic↗
PubMed1990

Effects of bopindolol on platelet function in hypertension at rest and during exercise.

The effects of bopindolol, a new nonselective beta-blocking agent, on platelet function have been studied in 10 male hypertensive patients given the drug (1 mg/day) in turn for eight weeks. Bopindolol significantly (p less than 0.01) decreased the bicycle exercise- (1.5 W/kg body weight for 6 minutes) induced increase in platelet aggregation. During bopindolol-treatment both the slope and the height of the platelet aggregation response curve were moderately decreased at rest before exercise and significantly (p less than 0.05) decreased at rest after exercise. During exercise the slope amounted to 75.4 +/- 44 degrees before and to 70.8 +/- 5.3 degrees after therapy (p less than 0.01), the height to 64.0 +/- 11.9% before and to 58.1 +/- 14.7% (p less than 0.05) after therapy. Furthermore, bopindolol significantly increased the exercise-induced decrease in platelet sensitivity to PGI2 (p less than 0.05; IC-50-value: 2.10 +/- 0.47 vs 1.88 +/- 0.31 ng/ml) and PGD2 (p less than 0.05; IC-50-value: (19.88 +/- 2.10 vs 18.57 +/- 1.63 ng/ml). Bopindolol also significantly (p less than 0.05) decreased the exercise-induced elevation in serum-TXB2 (244.9 +/- 35.2 vs 237.3 +/- 27.2 ng/ml) and plasma-TXB2 (15.7 +/- 6.3 vs 13.1 +/- 3.7 pg/ml). The platelet count, the plasma levels of 6-oxo-PGF1 alpha, beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) were not affected by bopindolol. It is concluded that bopindolol favourably affects platelet function, in that it lowers exercise-induced platelet aggregation and TXB2-formation in therapeutical doses and increases platelet sensitivity to antiaggregatory prostaglandins.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Additive benefit of PGI2 and PGE1 (via different mechanisms?) on inhibition of activation of human vascular smooth muscle cells?

It seems likely that the antiplatelet action of antiaggregatory prostaglandins (PGE1, PGI2) is not the pivotal mechanism of action involved in clinical improvement of peripheral vascular disease. Based upon earlier results that both of these agents may have a certain effect on proliferation of vascular smooth muscle cells, we approached that question of an "optimal therapeutic regimen" going one step further. Patients having to undergo amputation were given a randomized "last choice" therapy with either PGI2 (once or twice a day, 6 h, 5 ng/kg/min i.v.), PGE1 (once or twice a day, 1 ng/kg/min i.a.) or a combination of both with a 6 h interval in between for 5 consecutive days. The ones who underwent surgery had a pathomorphological examination of vascular segments removed during amputation. The counting of activated smooth muscle cells indicates a significant drop induced by both of the PG's alone. A second infusion a day with the same compound, however, did not induce a further decrease in the activation state. In contrast administering the complimentary PG caused a comparable, significant decrease (p less than 0.01) in activation of smooth muscle cells in the intima and the media as well. It thus seems, that different mechanisms may be involved inducing additive therapeutic benefit. PGI2 is hypothesised to act predominantly by blocking PDGF-release and interference with PDGF, whereas PGE1 may have a more direct vascular action. From these findings, as well as the beneficial clinical results to be reported elsewhere, a combined therapy by the infusion scheme used may be the optimal one for a PG-therapy at the moment, based upon platelet and smooth muscle cell action.

Age Factors↗
PubMed1989

Effects of Hydergine on platelet deposition on "active" human carotid artery lesions and platelet function.

Effects of co-dergocrine mesylate (Hydergine), a drug widely used for the therapy of cerebral vascular disease on local platelet accumulation in the carotid artery region was studied by means of the platelet uptake ratio (PUR) and on the systemic platelet-vascular wall interaction as calculated from platelet half-life were investigated. A placebo controlled, double blind, randomised protocol was used, 18 patients were treated with co-dergocrine and compared to placebo (n = 18). Co-dergocrine treatment resulted in a significant decrease in platelet deposition, PUR decreased from 1.28 +/- 0.05 before treatment to 1.25 +/- 0.06 on day 5 of therapy with a statistically significant (p less than 0.001) in the paired comparison. In the control group the corresponding changes from 1.29 +/- 0.04 before to 1.28 +/- 0.04 did not show a p-value of less than 0.05 in paired comparison. Platelet half-life (72 +/- 11 before vs. 76 +/- 11 hours after 5 days of co-dergocrine treatment) showed a statistically significant (p less than 0.001) prolongation, whereas in the placebo group no relevant change of T/2 was observed (71 +/- 10 before vs. 72 +/- 10 hours on day 5, p greater than 0.10). No relevant effects on ADP-induced platelet aggregation, platelet-release reaction, platelet aggregate ratio, TXB2 plasma levels and thrombin-induced MDA-formation could be detected. These results indicate that co-dergocrine decreased in-vivo platelet residence time to atherosclerotic lesions of the carotid artery. Co-dergocrine may thereby be of benefit in prevention of mural thrombus formation and prevention of transient ischemic attacks, but also of atherosclerosis in man.

Aged↗
PubMed1989

Isradipine: a potent calcium blocker with beneficial effects on platelet function and vascular prostacyclin production.

Calcium blockers inhibit platelet aggregation induced in vitro by various stimuli, such as ADP and collagen. In this study the in vitro effects of isradipine, a new dihydropyridine-derivative, and of nifedipine on platelet aggregation and malondialdehyde-production were tested. The lowest concentrations affecting ADP-induced platelet aggregation were 1.0 micrograms/ml isradipine and 12.5 micrograms/ml nifedipine. Both drugs exhibited an inhibitory action on malondialdehyde-production in concentrations 2 to 3 times lower than those affecting platelet aggregation. In vitro, PGI2-formation by rat aortic rings incubated with calcium blockers was increased in a dose-dependent manner. The lowest concentration of isradipine which increased PGI2-generation amounted 0.5 micrograms/ml. The corresponding value for nifedipine was 10 micrograms/ml. The findings demonstrate isradipine to be more potent than nifedipine in affecting in vitro platelet aggregation and enhancing PGI2-formation.

Adenosine Diphosphate↗
PubMed1989

Beneficial effect of long-term PGE1-treatment in left ventricular heart failure.

Five male patients aged 34-47 years with congestive heart failure showed an improvement of left ventricular ejection fraction (LVEF) at rather low PGE1-doses (10-30 ng/kg/min) without affecting blood pressure or heart rate. LVEF was estimated by means of radionuclide ventriculography (RNV) prior to and during i.v.-infusion of PGE1 at increasing dose rates (10-100 ng/kg/min). Therefore, we administered to these responders PGE1 at a rate of 20 ng/kg/min i.v. continuously on a long-term basis by means of a portable infusion pump. Until up to 4 months the remarkable benefit in LVEF induced by PGE1 was still present to a comparable extent in all the patients. No rebound desensitization phenomenon occurred either on platelet activity or on LVEF. PGE1, via a more practical route of application or by a stable analogue, may be a promising therapy at this stage of cardiomyopathy (CMP).

Adult↗
PubMed1989

Glucocorticoid-treatment does not influence the synthesis of thromboxane B2 and bicyclo-PGE2 in humans.

It has been reported that the anti-inflammatory action of glucocorticoids is due to the inhibition of phospholipases. Consequently, after high-dose steroid treatment in humans a decrease in cyclooxygenase products should be expected. In 15 patients (10 males, 5 females, 29-62 y) undergoing 6-methyl-prednisolone-treatment (40-80 mg daily) for various clinical reasons and in 5 healthy volunteers (4 male, 1 female, 28-37 y) receiving 500 mg 6-methyl-prednisolone daily for 3 days plasma- and serum-thromboxane B2 (TXB2), as well as bicyclo-prostaglandin E2 (bicyclo-PGE2) were monitored over 3 weeks. In the entire follow-up period, however, no significant change in either serum- or plasma-TXB2 or bicyclo-PGE2 could be measured in either, patients and volunteers, under glucocorticoid-treatment. These findings indicate that even high-dose glucocorticoid-treatment does not affect the serum- and plasma-metabolites of the eicosanoids examined. It is concluded that in humans a significant inhibition of phospholipases by glucocorticoids and subsequently reduced formation of cyclooxygenase products seems to be rather unlikely.

Adult↗
PubMed1989

Effects of taprostene, a chemically stable prostacyclin analogue, in patients with ischaemic peripheral vascular disease: a placebo controlled double-blind trial.

Thirty patients with ischaemic peripheral vascular disease and intermittent claudication were randomly allocated to receive either placebo or taprostene, a chemically stable prostacyclin analogue, intravenously at a rate of 25 ng/kg/min for 6 hours daily on 5 consecutive days. Taprostene produced a significant (p less than 0.05) increase in absolute walking time compared to placebo on one day after infusion and at 1, 4 and 8 weeks (14% vs 2.8%) later. Taprostene also produced a significant (p less than 0.05) increase in the pain-free walking time compared to placebo in the follow-up period (8 weeks after infusion: 23% vs 3.8%). During the infusion period systolic and diastolic blood pressure decreased (p less than 0.05) and heart rate was accelerated (p less than 0.05) in the taprostene treated group whereas no change was monitored in the placebo group. The ankle/brachial Doppler index was unaffected by taprostene. The platelet half-life was significantly (p less than 0.05) prolonged following taprostene-infusion (72.6 +/- 9.35 vs 77.9 +/- 7.44 hours). However, no change on platelet half-life was found in the placebo group (p less than 0.05). Various measures of platelet function parameters followed in vitro (ADP-induced aggregation, platelet sensitivity to PGI2, PGE1, PGD1 and taprostene, concentrations of platelet factor 4 and beta-thromboglobulin) showed no change with taprostene. Measures of circulating platelet aggregates and endothelial cells count showed no changes during the 2 months follow-up period too. It is assumed that taprostene may be of clinical benefit in patients with ischaemic peripheral vascular disease. However, future investigations have to be carried out to assess the optimal dose regime.

Alprostadil↗
PubMed1989

Pathomechanisms of atherosclerosis beneficially affected by prostaglandin E1 (PGE1)--an update.

The antiplatelet action of PGE1 was the basic concept for introducing this substance into clinical therapy of atherosclerosis. However, in the meanwhile a variety of other mechanisms have been discovered, which might be of importance, especially concerning the long-term benefit seen after treatment with PGE1, such as stabilization of endothelial lining, reflected by a decreased number of circulating endothelial cells and a decreased thrombogenicity (potentiated by endogenous EDRF-release), an inhibitory action on smooth muscle cells of the vessel wall such as decrease in mitotic and proliferative activity associated with a diminished extracellular matrix formation, an increase in fibrinolytic capacity, beneficial effects on white and red blood cells and some beneficial effects on the lipid metabolism by decreasing the arterial wall cholesterol content and upregulation of LDL-receptors as well as a moderate drop in serum cholesterol, seen in severe hypercholesterolemics only. It is assumed, that especially the vascular effects together with the hypolipidemic actions of PGE1 might be of major importance underlying the long-term benefit.

Alprostadil↗