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Biomedical subjects

V Wizemann

Publications and source records attributed to V Wizemann.

At least 19 recordsLinked to original sources

Protein adsorption by artificial membrane materials under filtration conditions.

Elevated plasma levels of numerous low molecular weight proteins (LMWP) in renal insufficiency are likely to contribute to the uremic syndrome. Dialysis-related amyloidosis, caused by the accumulation of beta 2-microglobulin (beta 2M), has highlighted the need for a renal replacement therapy that allows the elimination of LMWP in addition to small solutes. Synthetic membrane materials employed under hemofiltration conditions proved to be most effective in lowering elevated beta 2M plasma levels. In addition to convection, protein adsorption to artificial membrane materials is an important mechanism for beta 2M removal. Using an in vitro setup, 12 commercially available hemofilters representing 11 different membrane materials were perfused with human blood containing 125I-labeled plasma proteins. Under filtration conditions, total protein adsorption ranged from 338-2,098 mg/m2 of membrane surface, and the fraction of adsorbed LMWP varied between 14-70% of total protein adsorption and was negatively correlated to total protein adsorption. beta 2M adsorption showed up to an 8-fold difference between membranes, and was negatively correlated with total protein adsorption and positively correlated with the adsorption of LMWPs.

Adsorption

Influence of hydration state on plasma volume changes during ultrafiltration.

To assess the influence of hydration state on plasma volume (PV) changes during ultrafiltration, 11 clinically normhydrated patients on maintenance hemodialysis were studied intraindividually during 2 hydration states differing by 2-15% of lean body mass (LBM). Plasma volume was measured continually during a 15-min ultrafiltration test including an ultrafiltration of 1% of target weight and during a 45-min follow-up period of blood recirculation through the dialyzer without ultrafiltration. In all patients a maximal decrease in relative PV was more pronounced when there was less hydration and when the grade of hydration correlated inversely with the maximal response of PV decrease (r = -0.68, p < 0.001). The same was observed between the hydration state and the slope of the PV decrease (r = -0.69, p < 0.001). Plasma refilling was estimated in the period following ultrafiltration. The slope of the plasma volume increase correlated with the grade of hydration (r = 0.31, p < 0.05) as did the asymtote of PV (r = 0.4, p < 0.01). It is concluded that the less hydrated a dialysis patient is, the more pronounced will be the fall of the ultrafiltration-induced plasma volume and the less distinct will be the recovery of the plasma volume after the discontinuation of ultrafiltration.

Adult

Effect of erythropoietin on ischemia tolerance in anemic hemodialysis patients with confirmed coronary artery disease.

From a total of 81 patients on maintenance hemodialysis who underwent coronary angiography, 8 patients fulfilled the criteria: significant coronary artery disease, hematocrit less than 27%, reproducible (ECG) positive treadmill test, no disturbance of repolarization in ECG at rest. Exercise stress testing was performed at a hematocrit of 25 +/- 2% and following erythropoietin therapy at a hematocrit of 34 +/- 0.5%. Symptom-limited exercise performance increased in all patients (1.10 +/- 0.3 W/kg b.w. vs. 1.44 +/- 0.31 W/kg b.w., p less than 0.01) as well as exercise duration (489 vs. 362 s, p +/- 0.01). ST segment depression during maximal exercise was reduced from a mean of 2.1 to 0.4 mm (p less than 0.01). It is concluded that amelioration of renal anemia by erythropoietin in dialysis patients with significant coronary artery disease reduces exercise-induced myocardial ischemia.

Adult

Catecholamines and thrombocyte alpha 2-adrenoceptors in patients with acute myocardial infarction.

In 28 patients with first myocardial infarction plasma catecholamines and thrombocyte alpha 2-adrenoceptors were studied. The first determination (by HPLC and radioligand binding, respectively) was performed immediately after hospital admission and 6 weeks later. In the acute phase of myocardial infarction plasma adrenaline and noradrenaline levels were high. No significant differences in thrombocyte alpha 2-adrenoceptors and plasma concentrations of adrenaline and noradrenaline were observed between diabetic and non-diabetic patients. In three non-surviving patients only the affinity of the alpha 2-adrenoceptor to the radioligand was decreased (P less than 0.05), the relatively high catecholamine levels failed to reach statistical significance. Six weeks after hospital admission, adrenaline plasma levels were significantly decreased in diabetic and non-diabetic patients, while noradrenaline was only lowered in non-diabetic patients (P less than 0.05). Only in this group did the receptor number (BMAX) show a significant elevation 6 weeks after hospital admission. We conclude that, in acute myocardial infarction, alpha 2-adrenoceptors mainly interact with noradrenaline. Accordingly, no adrenoceptor alteration occurred in diabetic patients, who showed only a decrease in adrenaline but not in noradrenaline plasma concentrations 6 weeks following myocardial infarction. The different patterns in diabetic and non-diabetic patients suggest an alteration of catecholamine metabolism in diabetes mellitus.

Blood Platelets

Abnormal diastolic left ventricular filling by pulsed Doppler echocardiography in patients on continuous ambulatory peritoneal dialysis.

To determine characteristics of diastolic left ventricular (LV) function in patients on continuous ambulatory peritoneal dialysis (CAPD), two groups of CAPD patients without (n = 23; group 1) vs with (n = 25; group 2) LV hypertrophy (greater than 13 mm) were compared with a group of untreated non-renal hypertensive patients with LV hypertrophy (n = 11; group 3) using Doppler-echocardiography. Age and body surface area were comparable in all three groups, mean CAPD-duration (32 +/- 28 vs 26 +/- 23 months; p = NS) was comparable in renal patients. LV systolic function in echocardiography (LVEF: 62 vs 64 vs 63%) and systolic time intervals were normal and comparable in all three groups. Atrial maximum filling velocities (96 +/- 25 vs 91 +/- 25 vs 67 +/- 8 cm/s) were comparably increased, the ratio of maximal early/atrial filling velocities was comparably decreased (0.73 +/- 0.25 vs 0.77 +/- 0.21 vs 0.99 +/- 0.05) in both groups of renal patients as compared to group 3 (p less than 0.05-0.01). Atrial filling fractions were increased in all three groups, more pronounced in group 1 than in group 3 (50 +/- 11 vs 40 +/- 7%; p less than 0.05). The normal correlation of Doppler parameters with age and with LV radius/thickness ratio was altered in renal patients such that high patient age tended to have an additional negative influence on LV diastolic function of hypertrophied, but not of normal myocardium. Isovolumic relaxation time was prolonged in all three groups (134 +/- 38 vs 131 +/- 34 vs 116 +/- 17 ms; p = NS). We conclude that in patients on CAPD, diastolic LV filling is impaired both in normal and hypertrophied myocardium. High age is a factor that further attributes to diastolic dysfunction of hypertrophied myocardium in CAPD.

Age Factors

Cardiac structure and function in continuous ambulatory peritoneal dialysis: influence of blood purification and hypercirculation.

Continuous ambulatory peritoneal dialysis (CAPD) is associated with obvious hemodynamic and blood purification advantages over intermittent hemodialysis. To determine whether this is reflected in favorable left ventricular (LV) structure and function, a group of 55 normotensive patients (aged 58.4 +/- 11.0 years) undergoing CAPD was analyzed by means of echocardiography. Characteristic findings were LV hypertrophy (158 +/- 50 gm/m2), mainly the result of septal thickening (13.3 +/- 2.8 mm), and left atrial dilatation (40.9 +/- 7.4 mm). Mean LV diameter in end diastole and end systole and posterior wall thickness were normal. Parameters of LV systolic function (ejection fraction [EF]: 62.0 +/- 13.0%; velocity of circumferential fiber shortening [Vcf]: 1.58 +/- 0.46 circ/sec) were in the upper normal range at a hyperdynamic circulatory state (cardiac index [CI] 4.67 +/- 1.82 L/min/m2. The amount of LV hypertrophy was related to the amount of hypercirculation (CI: p less than 0.001; hemoglobin: p less than 0.025) and quality of blood purification (creatinine, urea: p less than 0.02) but not to blood pressure, age, or duration of dialysis. Left atrial dilatation was inversely related to LV systolic function (EF, Vcf: p less than 0.001) and directly related to LV muscle mass (p less than 0.02). A low prevalence (13%) of pericardial effusion was independent of blood purification. We conclude that in normotensive patients receiving CAPD, a high prevalence of left atrial dilatation and asymmetric septal hypertrophy is found, the latter being related both to the amount of hypercirculation and the quality of blood purification.

Adult

Time course of alpha 2-adrenoceptor desensitization induced by adrenaline infusion in man.

After a rapid increase in infusion rate of adrenaline to elevate the initial heart rate by more than 15%, a continuous infusion was sustained in order to maintain elevated adrenaline plasma levels. At the end of the first phase of the experiment, the thrombocyte alpha 2-adrenoceptor number (determined by radioligand binding) was significantly lowered. After the second part of the experiment, a further significant decrease in the density of binding sites was observed, while elevated adrenaline plasma levels were kept constant. The decrease in the number of binding sites was accompanied by a slight increase in affinity of the radioligand. Serum potassium concentration significantly decreased during the experiment, while other serum electrolytes showed no significant alterations.

Adult

Effects of a modified hemodiafiltration method on low-molecular-weight protein composition in plasma.

To assess the biochemical effects of a hemodiafiltration procedure where low-molecular-weight proteins can be removed from the plasma, 7 patients with end-stage renal disease were studied during a 6-month period of high-flux dialysis as well as during a succeeding 6-month period of hemodiafiltration. Distinct changes in the plasma protein composition occurred during the hemodiafiltration period, which cannot be explained solely as a result of molecular-weight-dependent filtration. Low-molecular-weight proteins in the plasma were reduced but losses of larger proteins occurred simultaneously. It is concluded that by increasing the dose of diffusive and convective transport in hemodiafiltration the renal tubular function in the catabolism of low-molecular-weight proteins cannot be replaced. The main obstacle to achieve such a goal appears to be the low selectivity of current high-flux membranes for low-molecular-weight proteins.

Adult

Plasma catecholamines and alpha 1-adrenoceptor function in hemodialysis-associated hypotension.

alpha 1-Adrenoceptor function and plasma catecholamine levels were investigated in chronically hemodialyzed patients with and without hemodialysis-induced hypotension. In the interdialytic period blood pressure responses as well as the mydriasis after topical application of the alpha 1-selective agonist phenylephrine were not significantly different in patients with or without hypotension during dialysis, although patients with hypotension were more susceptible to miosis induced by the muscarinergic agonist carbachol. In the normotensive group the blood pressure increasing effect of phenylephrine was attentuated after 120 min of hemodialysis therapy. Plasma noradrenaline levels were not significantly different in both groups and did not change significantly during hemodialysis, while plasma dopamine was significantly increased in the hypotensives. Thus, evidence for a pathophysiological role of a postsynaptic alpha-adrenoceptor dysfunction in hemodialysis-induced hypotension was lacking.

Blood Pressure

Increased concentrations of a circulating sodium pump inhibitor in essential hypertension and uraemia and its partial purification from haemofiltrate.

Patients with essential hypertension have 3.2 fold and patients with chronic uraemia 11.7 fold higher serum concentrations of endogenous digitalis-like activity than normotensives (76.3 +/- 9.3 nM). Upon haemodialysis this serum activity drops to almost normal values. A low molecular factor could be partially purified from 4000 l haemofiltrate.

Aged

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