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Biomedical subjects

F Rauscha

Publications and source records attributed to F Rauscha.

At least 19 recordsLinked to original sources
PubMed1992

Ticlopidine and platelet function in healthy volunteers.

The influence of a 4-weeks therapy with 500 mg ticlopidine daily on platelet function parameters was examined in 10 male healthy volunteers aged 20-33 years in order to extend the knowledge on the antiplatelet activity of this substance. Ticlopidine significantly (p less than 0.01) affected ex-vivo platelet aggregation induced by ADP and increased platelet sensitivity to the antiaggregatory action of PGI2. Generation of TXB2 from endogenous substrate during spontaneous clotting of blood (serum-TXB2), conversion of exogenous radiolabelled arachidonic acid into TXB2 and MDA-formation in isolated platelets were unaffected by the treatment. The TXB2-level in plasma of volunteers, however, was decreased, after administration of the drug. The diminished alpha-granule content liberation (beta-thromboglobulin: p less than 0.01; PDGF: p less than 0.01; PF4 not significant) indicates that ticlopidine induces a decrease in platelet activity. The beneficial effect on release reaction is not associated with a decrease in TXA2-formation. Our results demonstrate that ticlopidine inhibits platelet activity, especially the PDGF-release. These results confirm the value of this drug in the prevention of atherosclerosis and its thromboembolic complications.

Adult↗
PubMed1992

Modification of platelet function by isosorbide dinitrate in patients with coronary artery disease.

The effect of a four weeks oral treatment with 100 mg isosorbide dinitrate (ISDN) daily on platelet function was evaluated in 40 patients (aged 40-65 years) with proven coronary artery disease. Isosorbide dinitrate decreased platelet reactivity to ADP (p less than 0.001), increased platelet sensitivity to PGI2 (p less than 0.01) while the production of TXB2 from exogenous arachidonic acid substrate and from endogenous substrate were both significantly reduced. Circulating platelet aggregates as measured by the Wu-test were markedly reduced (p less than 0.001) but there was little change in the plasma concentration of the platelet proteins beta-thromboglobulin and platelet factor 4. Overall, platelet activation correlated with smoking, hypertension and a family history of coronary artery disease. The reduced platelet activation seen during treatment with isosorbide dinitrate may contribute to the therapeutic benefit seen with this drug in patients with coronary artery disease.

Adenosine Diphosphate↗
PubMed1992

Isradipine improves platelet function in hypertensives.

The effect of treatment for eight weeks with isradipine 1.25 mg twice daily for 4 weeks and thereafter 2.5 mg twice daily for 4 weeks on ex vivo platelet function was investigated in 10 male hypertensive patients, aged 51 (6.1) y. Systolic and diastolic blood pressure, platelet aggregation in response to ADP, serum thromboxane B2 and beta-thromboglobulin levels were significantly decreased at rest before exercise ergometry, during exercise and at rest after exercise. The platelet count, platelet sensitivity and the plasma levels of 6-oxo-prostaglandin F1 alpha were not affected by isradipine. It is concluded that a compound that lowers blood pressure and inhibits platelet activation may be of clinical benefit in the routine treatment of hypertension.

Analysis of Variance↗
PubMed1992

In vivo quantification of cholesterol content in human carotid arteries by quantitative gamma-camera imaging after injection of autologous low density lipoproteins (LDL).

Low density lipoproteins (LDL) were isolated by immunoaffinity chromatography from 18 patients (31-70 years) suffering from primary hypercholesterolemia with angiographically proven atherosclerosis of either one or both carotid arteries. LDL were labeled with 123I (1 mCi/mg LDL) by the iodine monochloride method followed by purification with dialysis and immediately reinjected thereafter. Gamma-camera serial controls over carotid regions allowed visual detection of uptake of the radiocompound uptake in 12 out of the 18 patients. The lipid entry ratio (LER; counts over the vascular region/pixel as compared to the contralateral side after background subtraction) confirmed the visual findings. Whole body images performed until 20 h after reinjection showed 3 different kinetic types of LDL-influx into the vessel wall: decreasing (type I), increasing and then decreasing (type II) and continuously increasing (type III) with time. Four patients underwent endarterectomy within 2-7 weeks after gamma-camera imaging. Histological control revealed an extensive amount of "foam cells" in tissue samples derived during surgery and an absence of endothelial lining in samples belonging to patients with type II kinetics.

Adult↗
PubMed1992

The diminished extracellular matrix production induced by isradipine, a calcium channel blocker, is completely abolished by cyclooxygenase inhibition.

Collagen and glycosaminoglycan synthesis are well known to be enhanced during early atherogenesis. In this experimental study the synthesis of collagen was determined using 14C proline incorporation, the glycosaminoglycan production by means of 35S-sulphate incorporation and subsequent quantification by means of autoradiography. Isradipine, a new calcium channel blocker of the dihydropyridine family at a dose of 0.3 mg/kg significantly (p less than 0.01) decreased the incorporation of both the radioactive precursors. This effect was abolished by a concomitant aspirin treatment, while aspirin alone did not exert any significant effect on the precursor incorporation. These data suggest that isradipine, which is known to stimulate PGI2 synthesis, may exert this antiatherosclerotic inhibitory action on extracellular matrix production via the endogenous liberation of PGI2.

Animals↗
PubMed1992

Prostaglandin I2 and the nitric oxide donor molsidomine have synergistic effects on thromboresistance in man.

1. In vitro synergistic effects of nitric oxide and prostaglandin I2 (PGI2) have been shown. Consequently we examined any potentiating effect of the nitric oxide donor molsidomine on the reduction in thrombogenicity produced by PGI2 in patients with peripheral vascular disease. 2. Thirty-six patients all with peripheral and also coronary artery disease were randomly allocated to receive PGI2 5 ng kg-1 min-1 for 6 h daily, 5 days a week for 5 weeks, alone (12 patients), with molsidomine 12 mg daily (12 patients) or molsidomine 12 mg daily alone (12 patients). 3. The effect of each treatment regimen was measured in terms of femoral artery platelet uptake and platelet survival after autologous 111Indium-oxine labelling. Molsidomine alone had no effect on platelet uptake or survival but in combination with PGI2 it significantly potentiated the decreased platelet uptake and prolonged platelet survival observed with PGI2 alone.

Aged↗
PubMed1991

Autologous low-density lipoprotein labelling allows characterization of human atherosclerotic lesions in vivo as to presence of foam cells and endothelial coverage.

The monitoring of local vascular kinetics after injection of autologous radiolabelled low-density lipoprotein (LDL) allows characterization of human atherosclerotic lesions as to the presence of foam cells and the quality of endothelial coverage. The following evidence exists: (1) dynamic imaging reveals two types of visual LDL accumulation in the vascular bed, one increasing, becoming visible sometimes only as late as after 24 h, and the other one appearing very early on, but decreasing with time; (2) the accumulation of iodine-123 LDL or iodine-131 LDL in the vascular bed shows three major types of local kinetic curves, which correlate with scintigraphic findings; (3) the accumulation of radiolabelled LDL in the vascular bed of humans in vivo is similar to its uptake in de- and re-endothelialized vessels of experimental animals using 125I-LDL; (4) morphological control in endarteriectomy samples confirms the hypothesis that this promising new approach may for the first time allow the in vivo monitoring of preclinical lesions in humans.

Adult↗
PubMed1991

Enhanced mitotic activity induced by irradiation is abolished by PGI2 pretreatment.

It is well known that irradiation may induce pronounced vascular lesions. Experimental studies revealed that irradiation induces an increased mitotic activity. As PGI2 has been claimed to be an antilesional agent, we wondered whether a pretreatment with PGI2 might abolish some of the effects induced by irradiation. 2 Groups of 24 rabbits were studied. 8 Rabbits each were irradiated with either 5 or 10 Gy on an abdominal aortic segment; 8 animals were sham treated. In each of the 3 groups half of the animals (n = 4) received PGI2 and half the buffer vehicle only. It is demonstrated that PGI2 is able to depress the enhanced mitotic activity induced by irradiation. In comparison to the controls, vascular thromboxane formation is decreased, the temporary increase in PGI2-formation by the vessel wall is less pronounced, whereas the conversion of exogenous arachidonic acid is unchanged. It is hypothetized that stable PGI2-analogues given during irradiation may probably prevent at least in part radiation-induced vascular changes and finally radiation-induced vasculopathy; this claim has to be proven in human.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

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

The effects of eight weeks of treatment with isradipine (1.25 mg twice daily for four weeks, followed by 2.5 mg twice daily for four weeks) on ex vivo platelet function were investigated in ten male patients with hypertension. Systolic and diastolic blood pressures, platelet aggregation in response to adenosine diphosphate (ADP), serum thromboxane B2, and beta-thromboglobulin levels were significantly decreased (P less than .05) at rest before exercise ergometry, during exercise, and at rest after exercise. The platelet count and plasma levels of 6-oxo-prostaglandin F1 alpha (PGF1 alpha) were not affected by isradipine. It is concluded that treatment of hypertension with a compound that lowers blood pressure and inhibits platelet activation may be of clinical benefit when routinely applied in hypertensive patients.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

13,14-dihydro-PGE1, an in-vivo metabolite of PGE1, decreases mitotic activity induced by corticosteroid administration.

PGE1 has antimitotic activity by virtue of its effect in increasing cAMP in vascular smooth muscle cells. The present study compares the effect of 13,14-dihydro-PGE1 (13,14-DH-PGE1) with PGE1 in an experimental model of stress induced by desoxycorticosterone in the rabbit. 13,14-DH-PGE1 significantly inhibited the stress-induced increase in mitotic activity, measured by autoradiography as percentage of 3H-thymidine positive cells, in all 3 abdominal aortic wall layers. Administration prior to stress was more effective than after stress, while combined administration was most effective. 13,14-DH-PGE1 exerts approximately 90% of the antimitotic activity of PGE1. It seems possible that the antimitotic activity observed after administration of intravenous PGE1 is attributable in part to 13,14-DH-PGE1.

Alprostadil↗
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

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↗
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↗
PubMed1988

[Defects in the prostaglandin system. VI. Acquired plasma factor defect].

A 44 year-old male was admitted to hospital in October 1984 presenting with enzymatic and electrocardiographic signs of posterior wall myocardial infarction. At this time 2 separate examinations revealed normal plasma factor activity. At the 1 year follow-up (November 1985) plasma factor activity was still present. However, in February 1987 for the first time, the patient's plasma failed to enhance PGI2 synthesis from vascular tissue in vitro. 3 further follow-up examinations within the next 6 weeks again revealed an acquired absence of plasma factor activity of unknown cause. No deterioration in clinical condition occurred. All relatives tested showed normal plasma factor activity.

Adult↗
PubMed1988

[Return to work following myocardial infarct].

The aim of this retrospective study involving 471 patients was to investigate the percentage of patients who returned to work after acute myocardial infarction. In the group of 350 patients who did not undergo subsequent aortocoronary bypass operation 70% returned to work, whereby half of these patients started work again within 6 months after infarction. A significantly higher number of patients who were enrolled in a cardiac rehabilitation programme returned to work as compared with patients not participating in such a programme (72% vs. 59%, respectively; p less than 0.04). There was, however, no difference between these 2 groups with respect to either the time point of resumption of work after myocardial infarction or the duration of employment between infarction and eventual retirement. Of the 121 patients who underwent an aortocoronary bypass operation, only 38% returned to work (p less than 0.001 vs. patients without bypass surgery).

Coronary Artery Bypass↗