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Biomedical subjects

V Wizemann

Publications and source records attributed to V Wizemann.

At least 55 records · Page 3Linked to original sources

Influence of an uremia-associated serum factor on CNS alpha 2-adrenoceptors.

The action of blood serum from uremic rats and chronically hemodialyzed patients was investigated for effects on alpha 2-adrenoceptors labeled with 3H-clonidine. Compared to blood sera of rats and patients with normal kidney function, uremic serum significantly inhibited specific 3H-clonidine binding. In saturation experiments the density and affinity of alpha 2-adrenoceptors for 3H-clonidine was lowered by uremic serum. Heating, or trypsin or lipase treatment of the serum did not affect this phenomenon. The effect of the patient's serum could likewise be demonstrated after hemodialysis treatment. The presence of an allosteric regulating substance for clonidine binding to adrenoceptors could at least partially explain the altered and attenuated action of this drug in renal insufficiency.

Animals↗

Asymmetric septal hypertrophy and left atrial dilatation in patients with end-stage renal disease on long-term hemodialysis.

Some literature reports associate a reduced weekly duration of treatment (3 x 4 h/week) for patients on maintenance hemodialysis with an increased cardiovascular mortality. To determine whether the improved survival of patients on long weekly hemodialysis (LHD: 3 x 8 h/week) can be associated with different cardiac changes, the cardiac characteristics of a group of 50 patients on LHD were analyzed in a non-invasive assessment. The main findings were an increased left ventricular (LV) muscle mass (176 + 54 g/m2), mass/volume ratio (1.69 + 0.37 g/ml) and left atrial diameter (39.7 + 5.7 mm). The increase in LV muscle mass was due mainly to a high prevalence of asymmetric septal thickening. The ratio septum/LV posterior wall was directly correlated with the left atrial diameter (r = 0.52), LV end-diastolic diameters were inversely correlated with hemoglobin concentration (r = 0.62). LV dilatation and/or LV systolic dysfunction were not characteristic findings: Only 6% of patients had a moderately enlarged (less than 65 mm) LV diameter, LV ejection fraction was decreased in 12%. There was no significant correlation between the degree of LV hypertrophy or left atrial dilatation and patient age, total dialysis duration, interdialytic weight gain, hemoglobin concentration, parameters of blood purification, blood pressure before and after dialysis, history of hypertension. We conclude that cardiac characteristics in patients on LHD are comparable to those described for large patient groups on short hemodialysis. Our findings do not explain improved survival on LHD.

Adult↗

Catecholaminergic and muscarinergic receptors in chronic experimental uremia.

In chronic uremic rats the density of alpha 1- and alpha 2-adrenoceptors in the cerebral cortex was significantly increased while beta-adrenoceptors and muscarinergic receptors in heart and brain as well as cardiac alpha 1-adrenoceptors were unchanged. Only the binding of the alpha 2-selective ligand 3H-clonidine was inhibited by uremic serum. In isolated left ventricular muscle strips dose-effect curves of (-)-noradrenaline and (+/-)-dobutamine were not significantly different in uremic and control animals whereas the negative inotropic action of the muscarinergic agonist carbachol was attenuated.

Animals↗

Search for optimizing dialysis therapy. I. Acute effects of hemodiafiltration with a highly permeable membrane and a large dose of convection and diffusion.

Based on the concept that an optimisation of dialysis therapy might be achieved by increasing the removal of small metabolic substances as well as low molecular weight proteins, hemodialfiltration (HDF) was modified. In 9 ESRD patients, HDF was performed acutely for 4 h, where 60 liters of substitution fluid were infused per patient. Two polysulphone F60 membranes in line were used as hemodialfilters. As compared to conventional hemodialysis (HD), performed with a cuprophane dialyser, HDF resulted in higher extraction indices for small solutes assessed by HPLC. Due to the large amount of convection applied, HDF was followed by significant decreases of low molecular weight proteins ranging from 9.5 kdaltons (iPTH, p less than 0.01) to 17 kdaltons (myoglobin, p less than 0.01). Analysis of the protein pattern of the serum revealed a nonlinear function in the decrease of plasma proteins after HDF. It is concluded that even though the detoxification efficacy of the described HDF method is by far superior to conventional HD in quality and quantity, the efficacy is still far from that of excretory renal function. Thus, to further improve efficacy with respect to the catabolic renal function for low molecular weight proteins, membranes for HDF or hemofiltration barriers but should surpass the sieving properties of the glomerulus in the low molecular protein range.

Adult↗

Adenylate cyclase and alpha-2-adrenoceptors in thrombocytes of chronic uremic patients.

Thrombocyte adenylate cyclase regulation and alpha-2-adrenoceptors have been studied in uremic patients as well as in healthy controls. Stimulation of adenylate cyclase activity by PGE1 and forskolin as well as inhibition by (+/-)-epinephrine was not significantly different between both groups. Additionally, there was no evidence of an alteration of the thrombocyte alpha-2-adrenoceptor density, determined by 3H-rauwolscine binding as suggested by others.

Adenylyl Cyclases↗

Analysis of left-ventricular changes associated with chronic hemodialysis. A noninvasive follow-up study.

To assess the reasons for the frequent cardiovascular complications in patients with end-stage renal disease (ESRD), 61 out of 131 normotensive ESRD patients originally examined (mean ESRD duration: 71 +/- 41 months) were followed over 2.5 years by echo-, electro- and mechanocardiography. Clinical and biochemical parameters were comparable. The prevalence of pericardial effusion (3%), pericardial thickening (14%), aortic valve sclerosis (14%) and mitral valve anulus sclerosis (12%) was unchanged. The interventricular septum diameter (14.3 +/- 3.0 vs. 16.4 +/- 3.4 mm), index of left-ventricular (LV) wall asymmetry (1.25 +/- 0.30 vs. 1.52 +/- 0.36) and left atrial diameter (38.3 +/- 5.4 vs. 42.6 +/- 3 mm) increased (p less than 0.001). The LV end-systolic diameter decreased slightly (35.8 + 6.3 vs. 34.2 +/- 6.4 mm; p less than 0.05), with no significant changes for end-diastolic diameter (50.4 +/- 6.3 vs. 49.3 +/- 6.1 mm), muscle mass index (189 +/- 57 vs. 197 +/- 50 g/m2), stroke volume (86.1 +/- 26.2 vs. 85.7 +/- 26.7 7 ml/m2) and fractional shortening (29.1 +/- 7 vs. 30.8 +/- 8.6%). We conclude that the predominant finding in ESRD is an LV hypertrophy progressing towards an asymmetric septum hypertrophy, while the increase of the primarily enlarged left atrial diameter over 30 months reflects a further deterioration of the diastolic LV dysfunction.

Cardiomegaly↗

Interactions of heparin with alpha-2-adrenoceptors.

The interactions of the anticoagulant Heparin with the alpha-2-adrenoceptor in rat brain cortex membranes were investigated. Binding experiments with 3H-Clonidine were performed in both the absence and presence of Heparin. 1 uM Na-Heparin caused a significant decrease in the maximal number of binding sites (Bmax) from 129.4 fmol/mg protein to 93.7 fmol/mg protein with an associated decrease in affinity (KD = 0.79 pM vs. KD = 1.53 pM) of these binding sites. Addition of Na+-Heparin to 3H-Clonidine (3.1 nM) labelled membranes inhibited 50% of specific 3H-Clonidine binding (IC50) at a concentration of 0.95 uM. Based on our findings we conclude that the simultaneous long term administration of Na-Heparin and the antihypertensive agonist Clonidine should be regarded under consideration of the inhibitory effect of Na-Heparin to the alpha-2-adrenoceptors.

Animals↗

Sodium pump inhibitor in the serum of patients with essential hypertension and its partial purification from hemofiltrate.

A 3-fold higher concentration of "endogenous digitalis" is found in the serum of patients with essential hypertension than in the serum of normotensives, whose concentration was determined in 22 normotensive probands by an receptor assay using isolated (Na+ + K+)-ATPase as 76.3 +/- 9.3 nM ouabain equivalents. Since the concentration of "endogenous digitalis" was 7-19 fold higher in 2 patients, who had become uremic due to a malignant hypertension and since their serum levels fell 3-fold by hemodialysis, the hemofiltrate was used for partial purification of the substance. This was possible by hydrophobic chromatography on Amberlite XAD-2, octadecyl-coated silica gel, anion exchange chromatography and affinity chromatography on membrane-bound (Na+ + K+)-ATPase. The partially purified substance behaved like the material described by Cloix et al. (1985) Biochem. Biophys. Res. Commun. 131:1234-1240 and competed with digoxin for digoxin antibodies. Ascorbic acid isolated on the search for an inhibitor of (Na+ + K+)-ATPase from beef brain inhibited [3H]ouabain binding due to a decrease of the ouabain binding sites by a reduction of a group within the ATP binding site of the enzyme. Unsaturated fatty acids claimed to be "endogenous digitalis (Tamura et al. [1985] J. Biol. Chem. 260:9672-9677)" also lowered the capacity of the cardiac glycoside binding site but did not compete with ouabain.

Animals↗