Search PubMed⌕ Search

Biomedical subjects

H Sinzinger

Publications and source records attributed to H Sinzinger.

At least 235 records · Page 13Linked to original sources
PubMed1992

Aspirin abolishes the decreased low-density lipoprotein (LDL) entry into the rabbit arterial wall induced by the calcium channel blocker isradipine.

After deendothelialization and experimentally induced hypercholesterolemia in rabbits, an increased LDL entry into the vascular wall can be monitored using radiolabelled LDL. In male rabbits aged 6 months the abdominal aortic endothelium was removed by a Fogarty catheter. The animals fed a 1% cholesterol supplemented diet were treated either with isradipine (0.3 mg/kg/daily) (n = 36) alone or in combination with aspirin (5 mg/kg/daily) (n = 36) for four weeks. Thirty-six animals served as controls. 1, 3, 6, 12, 24 and 48 hours prior to sacrificing, 10 microCi 125I-LDL was administered intravenously to six rabbits in each group. The LDL entry was quantified in the abdominal aorta according to morphologically assessed type of surface lining. Aortic cholesterol content was assessed by Sudan-III staining and quantitative determination. Endothelialized segments exhibited a significantly (p less than 0.05 - p less than 0.001) lower LDL uptake as compared to re- or deendothelialized segments. The LDL entry was significantly lower with isradipine treatment than in controls. In parallel the cholesterol content decreased and the Sudan-III-positive areas were smaller in size. This beneficial effect as well as that on aortic lipid content was abolished by a pretreatment with aspirin. While in the isradipine-treated animals PGI2 synthesis was significantly (p less than 0.01) enhanced, it was almost completely blocked by aspirin. These findings indicate that the benefit of reduced LDL entry caused by isradipine may be mediated by an increased endogenous PGI2 synthesis.

Animals↗
PubMed1992

[Economic aspects of therapy for lipid metabolism disorders].

The primary and secondary prevention of cardiovascular diseases and, therefore, the therapy of hyperlipidemia is essential in strategies to lower morbidity and mortality from coronary heart disease (CHD), the most relevant atherosclerosis-associated disease. These programs imply not only a medical but also an economic challenge to our health system. That is why all therapeutic measures have to be evaluated regarding their cost-effectiveness. A cost-effectiveness profile was calculated for all the therapies of hyperlipidemia (nutritional therapy, dietetic nutritionals, drugs and LDL-apheresis) with respect to the following parameters: total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides. The daily costs of all interventional measures are compared to the success rate, whereby an index of daily therapy costs and 1% change per lipid parameter was calculated. Nutritional therapy is by far the cheapest, and LDL-apheresis the most expensive but also the most effective and reliable therapeutic measure. It has to be considered, however, that dietary intervention can be very successful in overnutrition while in rare cases of severe homozygous familial hypercholesterolemia there is no therapeutic alternative to LDL-apheresis. Life-style modifications, such as changing nutritional habits, may contribute towards reducing or removing one or more risk factor(s) (e.g. malnutrition is associated with overweight, hyperlipoproteinemia (HLP), hyperinsulinemia (syndrome X), hyperfibrinogenemia and hypertension). But neither health politicians nor the population seem to be conscious of the fact that life-style changes help to reduce medical expenditure. Considering the fact that nearly every medical service is getting more and more expensive, the need to introduce financial regulations is evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol↗
PubMed1991

Platelet survival in patients with dilated cardiomyopathy.

Dilated cardiomyopathy is associated with thromboembolic complications, which correlate poorly, however, with a visible left ventricular thrombus. Therefore, this study was performed to assess whether an abnormality of platelet function in vivo can be detected in patients with dilated cardiomyopathy. Platelet survival was measured after autologous labeling with indium-111 oxine in 28 patients with dilated cardiomyopathy and angiographically normal coronary arteries (mean ejection fraction 21 +/- 9% [standard deviation], range 4 to 39%) and in nine patients with coronary artery disease and similar left ventricular dysfunction (mean ejection fraction 21 +/- 10%). Plasma levels of beta-thromboglobulin and platelet factor 4 were measured in patients with idiopathic cardiomyopathy (n = 15) and platelet scintigraphic images of the heart (n = 24) were obtained in subsets of both patient groups. Platelet survival was significantly and similarly shortened in patients with idiopathic and ischemic cardiomyopathy (67 +/- 34 and 55 +/- 24 h, respectively) compared to controls (209 +/- 9 h, n = 12; p less than 0.001). Of the two platelet-specific proteins, beta-thromboglobulin was increased in the patients compared with controls (42 +/- 17 versus 22 +/- 6 ng/ml, p less than 0.001). Platelet scintigraphy 24 h (n = 24) and/or 48 h (n = 9) after labeling showed a diffuse pattern of enhanced platelet uptake over the heart which varied in intensity among patients, but which was never seen in controls (n = 6). This increased platelet uptake was similar in patients with idiopathic and ischemic cardiomyopathy but did not correlate with either ejection fraction or cardiothoracic ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Interaction between prostaglandin E1 and nitric oxide (NO).

A synergistic antiplatelet effect between prostaglandin I2 (PGI2), a cAMP-stimulator, and nitric oxide (NO), a cGMP-stimulator, has been described. Data on a PGE1-NO interaction, however, are lacking so far. We therefore examined the question in healthy volunteers, whether a similar synergism exist between PGE1 and NO on human platelets in vitro. Each of the substances alone caused a dose-dependent inhibition of ADP-induced platelet aggregation, PGE1 (1ng/mlPRP) reduced platelet aggregation by 27.8 +/- 14.6%, NO (0.3%) by 26.7 +/- 25.5%. The combination of these compounds caused an additive effect resulting in a reduction of 40.6 +/- 23.5%. The findings indicate that PGE1 (like PGI2) and NO have a synergistic antiplatelet action. The concomitant treatment with both compounds offers an interesting concept for clinical therapy.

Adult↗
PubMed1991

Platelet lipoxygenase defect (Wien-Penzing defect) in two patients with myocardial infarction.

In 2 male patients (35 and 38 years) presenting with myocardial infarction an abnormal conversion of exogenous 14C-arachidonic acid by the patients' platelets, incubated in vitro, was observed. Neither patient's platelets showed evidence of a lipoxygenase pathway. Platelet thromboxane formation from exogenous and endogenous substrate was high, while the platelet aggregation responses were normal. A myeloproliferative syndrome was excluded by bone marrow puncture. Similar defects have only been described so far in patients with myeloproliferative syndrome. This defect may be causative for the onset of clinical thrombotic events. It is speculative whether in vivo therapy with r-IFN alpha 1c might be able to eradicate the pathological platelet clone.

Adult↗
PubMed1991

Low density lipoprotein labelling characterizes experimentally induced atherosclerotic lesions in rabbits in vivo as to presence of foam cells and endothelial coverage.

The entry of autologous iodine-125 low density lipoprotein (125I-LDL) into the aortic wall in rabbits was measured. After abdominal endothelium abrasion with a Fogarthy catheter the animals were fed a 1% cholesterol-supplemented diet for 4 weeks. The animals were killed 1-48 h after administration of 25 muCi 125I-LDL. Local entry of radiolabelled LDL was estimated and correlated to endothelial surface lining and foam cell content, both controlled morphologically. Endothelialized segments showed the lowest entry of 125I-LDL, the maximum uptake was reached at around 8 h. In de-endothelialized segments the entry was higher and the peak later (12 h), while in re-endothelialized segments a continuous increase in 125I-LDL entry up to 48 h was measured. Number and extent of foam cells correlated with the entry of LDL. The data indicate the usefulness of LDL radiolabelling for qualitative in vivo information on surface lining and foam cell content.

Animals↗
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

Influence of no-donor (SIN-1) on functions of inflammatory cells.

NO-donor SIN-1 (0.01-1.0 mM) dose-dependently inhibited the basal and FMLP (30.0 mM)-stimulated release of beta-glucuronidase from rat peritoneal leukocytes and antigen-specific stimulation of Interleukin-2 production by T-hybridomas. I-123 LDL binding to human lymphocytes was inhibited by Iloprost (1 mM) but activated by SIN-1 (0.3 mM). We conclude that beside the smooth muscle cells and platelets the blood inflammatory/immune cells are under the PGI2/NO control, however, the precise regulation as well as physiological importance need further investigation.

Animals↗
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

Effect of prostaglandin E1 on low density lipoprotein apo-B-receptor binding in human, rat and swine liver in vitro.

The effect of PGE1 on low density lipoprotein (LDL) apo-B-receptor binding was examined in human, rat and swine liver. Autologous LDL (for humans and swines) and homologous LDL (for rats) were isolated by ultracentrifugation and labelled with 123I using Iodogen followed by purification with dialysis. LDL-concentrations of 0.1-6 micrograms protein/ml were used for direct binding assays investigating the specific binding of labelled LDL in presence of increasing PGE1-concentrations (100 pM to 100 microM). In separate experiments the effect of PGE1 on displacement of specifically bound 123I-LDL by unlabelled ones was studied. The binding capacities estimated by Scatchard analysis were similar for human and rat liver LDL-apo-B-receptor binding, however, swine liver exhibited a significantly (p less than 0.001) lower binding capacity for 123I-LDL. PGE1 significantly (p less than 0.01-0.001) increased the amount of 123I-LDL specifically bound to the liver apo-B-receptors and the binding affinity in all liver preparations of the 3 species in a dose-dependent manner. PGE1 also significantly increased competition of unlabelled LDL for 123I-LDL bound to its specific apo-B-receptors in a dose-dependent manner (p less than 0.01-0.001) with an ED50 of 123 +/- 64 nM for human liver, 901 +/- 102 nM for rat liver obtained during anaesthesia, 74 +/- 23 nM for rat liver obtained after decapitation and 941 +/- 121 nM for swine liver. In human liver iloprost (ED50 = 876 +/- 53 nM) and PGI2 (ED50 = 52 +/- 12 microM) were less effective than PGE1, PGE2 had no effect on LDL-induced competition. It is concluded that PGE1 renders LDL more sensitive for apo-B-receptor binding suggesting a potential hypolipidemic action of PGE1.

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

Comparison of different methods for LDL isolation and radioiodination on liver LDL receptor binding in vitro.

Lipoproteins were isolated either by immunoaffinity chromatography (LDL and VLDL) or ultracentrifugation (LDL). Purified lipoproteins were labeled with 123I using either Iodogen or iodine-monochloride (IC1) each followed by purification with gel-chromatography or dialysis (total of 4 combinations). Lipoprotein-concentrations of 0.1-6 micrograms protein/mL were used for direct binding assays investigating the specific binding of labeled lipoproteins (in the presence of a 50-fold excess of unlabeled lipoproteins) to human liver apo-B, E-receptors. In separate experiments displacement of bound 123I-lipoproteins (labeled by the methods mentioned) by unlabeled ones was studied. The binding capacities estimated by Scatchard analysis were similar to each other (141-163 ng protein bound/mg liver plasma membrane protein) independent from the method used for isolation and labeling. Also the affinity constants were very similar and ranged from 0.9 to 1.7 micrograms protein/L. It is concluded that immunoaffinity chromatography or ultracentrifugation for isolation of lipoproteins and the Iodogen or IC1-method for radiolabeling can be recommended to be equally good for in vitro receptor investigation.

Adult↗
PubMed1991

Thiopental and ether anaesthesia decrease the prostaglandin receptor density of the rat liver.

Male Sprague-Dawley rats were killed either by decapitation or during anaesthesia with thiopental or diethylether by aortectomy. Livers were removed and liver plasma membranes were prepared using standard techniques. Direct binding experiments with 3H-PGE1 and 3H-iloprost revealed heterogeneity of the binding sites (high and low affinity binding sites), whereas 3H-PGE2 demonstrated only high affinity binding to the liver. The highest binding capacity for all radioligands was found for livers after decapitation. Livers obtained during anaesthesia showed a significantly (p less than 0.05 to p less than 0.001) lower binding capacity and binding affinity for 3H-PGE1, 3H-PGE2 and 3H-iloprost. The reduction in binding activity was more pronounced in livers obtained during inhalation than thiopental anaesthesia. Specific binding amounted to 82.1 +/- 7% for 3H-PGE2, 75.3 +/- 9% for 3H-PGE1 and 78.9 +/- 8% for iloprost in livers obtained after decapitation. In livers obtained during anaesthesia specific prostaglandin binding was significantly (p less than 0.01) decreased, again being more pronounced during inhalation than thiopental anaesthesia. These results suggest that some anaesthetics interfere with prostaglandin receptors of the liver.

Alprostadil↗
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↗