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Biomedical subjects

P Fitscha

Publications and source records attributed to P Fitscha.

At least 19 recordsLinked to original sources
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

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↗
PubMed1992

Antiatherosclerotic actions of isradipine.

Isradipine, a calcium antagonist of the dihydropyridine type, shows antiatherosclerotic actions that interfere with all three main mechanisms of atherosclerosis. These actions are mediated by the release of prostaglandin I2 and endothelium-derived relaxing factor, and the subsequent elevation of intracellular adenosine-3',5'-cyclic phosphate and 3',5'-guanosine monophosphate, respectively. These mechanisms have been proven in vitro and in animal models. Preliminary data in humans suggest that these mechanisms have clinical relevance in the long-term treatment of patients as well.

Arteriosclerosis↗
PubMed1991

Intravenous prostacyclin (PGI2) infusion to 108 patients with ischaemic peripheral vascular disease: phase II-open study.

We recently reported the results of a double-blind trial of PGI2 in 108 patients with ischaemic peripheral vascular disease Stage II according to Fontaine. They were randomly allocated to receive an intravenous infusion of either PGI2 (6 ng/kg/min over 8 hours daily for 5 consecutive days) or placebo and classified as treatment responders or non-responders on the basis of changes in absolute and relative walking times. Patients treated with placebo and those who did not improve in this double blind trial entered an open trial in which they all received infusion of PGI2 (6 ng/kg/min over 8 hours daily for 5 consecutive days). The results of this open trial are reported here. Patients who had been allocated to PGI2 in the blind trial had significantly (p less than 0.01) longer walking times as compared to placebo-treated patients prior to receiving the second (PGI2) infusion. PGI2-infusion caused significant (p less than 0.01) prolongation of walking times in both groups up to the 2nd follow-up month. One month after infusion 52% (23 patients) of the initially placebo-treated patients and 31% (14 patients) of the initially PGI2-treated patients were scored as positive treatment responders (p less than 0.01).

Aged↗
PubMed1991

Antihypertensive effects of isradipine and captopril as monotherapy or in combination.

The antihypertensive effects of isradipine and captopril were studied in 140 patients (70 men) with mild-to-moderate hypertension, aged 26 to 74 years, in a double-blind, randomized, between-patient comparative trial. Initial treatment started with 1.25 mg isradipine twice daily or 12.5 mg captopril twice daily. If normotension was not achieved after four weeks, doses were increased to 2.5 mg twice daily or 25 mg twice daily, respectively. If the maximum dose as monotherapy did not result in normotension, captopril (12.5 mg or, if necessary, 25 mg twice daily) was added to regimens of the isradipine-treated patients or isradipine (1.25 mg or, if necessary, 2.5 mg twice daily) was given in addition to the captopril-treated patients. After 24 weeks of active treatment, systolic blood pressure was significantly reduced (P less than .001) with isradipine (from 168 +/- 18 to 144 +/- 14 mm Hg) and with captopril (from 168 +/- 20 to 143 +/- 10 mm Hg). Diastolic blood pressure also fell significantly (P less than .001) in both groups (isradipine: from 105 +/- 5 to 84 +/- 5 mm Hg; captopril; from 105 +/- 4 to 85 +/- 4 mm Hg). With isradipine as monotherapy, diastolic blood pressure was normalized in 49% of patients compared with 56% with captopril as monotherapy (P = NS). Combining both drugs resulted in an increased rate of normalization (to 87%). The results indicate that combined treatment with a calcium antagonist and an angiotensin-converting enzyme inhibitor is effective in lowering blood pressure and is well tolerated during long-term therapy.

Adult↗
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

Isradipine, a calcium-entry blocker, decreases vascular [125-I]low-density lipoprotein entry in hypercholesterolemic rabbits.

In 72 male rabbits aged 6 months, the endothelium of the abdominal aorta was abraded by a Fogarthy catheter. The animals were then fed a 1% cholesterol-supplemented diet for 4 weeks. In addition, half of the animals were treated for the entire period with isradipine (0.3 mg/kg daily), a dihydropyridine calcium antagonist; the other 36 animals served as controls. One hour and 3, 6, 12, 24, and 48 hours before the animals were killed, [125-I]low-density lipoprotein (LDL 10 microCi) was administered intravenously (i.v.) to six animals in each group. The [125-I]LDL entry was quantified in the abdominal aorta according to the type and presence of endothelial lining. Isradipine significantly reduced the [125-I]LDL entry at most time intervals. In parallel, an increase in vascular prostaglandin (PGI2) synthesis was noted, which might be the underlying mechanism for the decreased LDL entry.

Animals↗
PubMed1991

Evaluation of isradipine and captopril alone or in combination for the treatment of hypertension.

The antihypertensive effects of isradipine and captopril were studied in 231 patients with mild-to-moderate hypertension in a double-blind, randomized, between-patient trial. Treatment was started with 1.25 mg of isradipine or 12.5 mg of captopril twice daily which, if normotension was not obtained, was increased after 4 weeks to 2.5 mg or 25 mg twice daily, respectively. If the maximum dose of each drug alone did not result in normotension, captopril (12.5 mg or, if necessary, 25 mg twice daily) was added to the isradipine regimen, and isradipine (1.25 mg or, if necessary, 2.5 mg twice daily) to the captopril regimen. Following 24 weeks of active treatment, systolic blood pressure (SBP) was significantly (p less than 0.001) reduced by isradipine (170 +/- 17 vs. 153 +/- 17 mm Hg) and by captopril (170 +/- 19 vs. 155 +/- 19 mm Hg). Diastolic blood pressure (DBP) also fell significantly (p less than 0.001) in both groups (isradipine: 106 +/- 5 vs. 93 +/- 8 mm Hg; captopril: 106 +/- 5 vs. 95 +/- 10 mm Hg). After isradipine as monotherapy, DBP was normalized in 49% of patients compared with 52% after captopril monotherapy. Combination of both drugs increased the normalization rate to 84%. The results indicate that combined treatment with a calcium antagonist and an angiotensin-converting enzyme (ACE) inhibitor is effective in lowering blood pressure, and is well tolerated as long-term therapy.

Adult↗
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

Decreased prostaglandin-I2 stability in acute myocardial infarction.

It has been demonstrated that under certain conditions the in-vitro half-life of biologically active PGI2 in plasma is extremely shortened, which may result in-vivo in a local haemostatic imbalance. In 36 patients suffering from acute myocardial infarction a sequential change in in-vitro half-life of synthetic PGI2 was therefore studied during 3 weeks. 21 patients admitted turning out not to develop myocardial infarction served as follow-up controls. During and shortly after the acute episode the plasmatic half-life of PGI2 in-vitro was shortened by about 40%, improving continuously thereafter. No certain influence of either risk factors, sex or age could be discovered. A possible influence of various drugs administered in the hospital period has been excluded in 43 patients with proven coronary artery disease. No such changes occurred during acute angina pectoris attack in 12 patients. It remains to be established, whether the short-lasting destabilisation of PGI2 may be an acute disease-associated finding, or an important pathogenetic factor.

Aged↗
PubMed1990

Platelet kinetics in patients with atherosclerosis.

In 12 patients (8 males, 4 females; 59.4 +/- 6.2 years) with clinically manifest atherosclerosis (peripheral vascular disease stage II according to Fontaine and coronary heart disease) without any risk factor and 6 controls (4 males, 2 females; 58.5 +/- 7.06 years) autologous platelets were labelled using 100 microCi 111-In-oxine. In parallel, serum- and plasma-thromboxane (TX) B2 and conversion of exogenous radiolabelled arachidonic acid towards TXB2 were determined. No difference in labelling efficiency and recovery was noted. Platelet half-life was significantly (p less than 0.01) shortened in the atherosclerotics. Gamma-camera images were obtained during the first 64 minutes after reinjection as well as 2, 6, 18, 24 and daily up to 1 week after reinjection of autologous radiolabelled platelets. No difference between the patients suffering from atherosclerosis--having either visible atherosclerotic lesions or not--could be discovered. Serum-TXB2 was comparable, whereas plasma-TXB2 showed a trend towards an increase and the conversion from exogenous 14C-AA to 14C-TXB2 was increased in atherosclerosis.

Arachidonic Acid↗
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↗