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Biomedical subjects

M M Müller

Publications and source records attributed to M M Müller.

At least 91 records · Page 5Linked to original sources
PubMed1994

Therapeutic whole-blood levels of cyclosporin A in heart and lung transplantation.

The use of cyclosporin A (CyA) as an immunosuppressive drug is limited because of its serious side effects. In order to minimise these toxic side effects while utilising immunosuppressive properties of CyA, the dosage of CyA is generally administered on the basis of the individual CyA whole blood level. Therefore, a frequent determination of CyA whole blood levels is necessary. The aim of our study was to establish therapeutic whole blood levels for patients after heart (HTX) and lung (LuTX) transplantation depending on the interval of time after transplantation. CyA levels were determined by HPLC and by fluorescence polarisation immunoassay (FPIA) with a monoclonal and a polyclonal antibody. Two hundred and ninety-five patients after HTX and 48 patients after LuTX were investigated and patients with rejection and/or pathological kidney and liver function were excluded. No significant differences between the two groups of patients were detected. Therefore, common therapeutic ranges for CyA can be used for adequate immunosuppression for patients after HTX and LuTX.

Antibodies, Monoclonal↗
PubMed1994

Influence of purines on endothelial high energy phosphates.

It was demonstrated that extracellularly available adenosine, which is reported to protect the endothelium during ischaemia and reperfusion [8], is predominantly uptaken and salvaged by HUVECs, thereby enriching the adenine phosphate pool. In this way adenosine could contribute to a regeneration of metabolically disturbed cells via increasing the intracellular ATP. In contrast, all other purines offered can hardly be used by HUVECs to increase the pool of energy rich phosphates.

Adenosine Diphosphate↗
PubMed1994

Endothelial cells' responses to hypoxia and reperfusion.

Our results suggest that longer periods of hypoxia lead to a deficiency of high energy phosphates. Reoxygenation leads to the formation of ROS, irrespectively of the duration of hypoxia. It might be concluded that a diminished level of intracellular high energy phosphates upon hypoxia followed by oxidative stress plays a key role in the reperfusion associated cellular dysfunctions.

Adenosine Triphosphate↗
PubMed1994

Failure mode of a new pericardial valve prosthesis (Sorin Pericarbon). A morphological study.

Between February 1986 and February 1992, 144 patients (mean age 69 years) received 149 bovine pericardial valve bioprostheses (Sorin Pericarbon). Out of this group 10 patients required reoperation because of valvular dysfunction. Defect bioprostheses (7 aortic valves, 3 mitral valves), removed 34 to 81 months after implantation, were studied by X-ray analysis as well as light and electron microscopy. Seven out of ten valves were explanted because of valvular stenosis, two valves had to be replaced because of valvular regurgitation and one because of paravalvular leakage. X-ray analysis revealed severe clacification of the cusps in all cases. Mineralization occurred predominantly next to commissural attachment zones. Cuspal tearing, associated with calcific degeneration of the tissue, was observed in two cases. Beside the commissures, accelerated tissue degeneration could be detected near the basal suture line: disintegration of collagen bundles by invading macrophages and mineral deposits was prominent in these regions. Scanning electron microscopy revealed the presence of circumscribed areas of endothelial-like cell lining on both surfaces of the cusps of five explants. Valvular stenosis, caused by severe calcification of commissural as well as basal regions of the leaflets, is the principal failure mode of the Sorin Pericarbon heart valve prostheses. As an additional aspect, the basal suture line must be assumed to be a critical determinant in accelerating tissue degeneration. Long-term clinical studies will be required to evaluate the clinical performance of this valve, focusing on thromboembolic complications, hemodynamic function and long-term durability.

Aged↗
PubMed1994

In vitro effects of hypoxia and reoxygenation on human umbilical endothelial cells.

We investigated metabolic changes in human umbilical venous endothelial cells, when these were incubated under hypoxic followed by hyperoxic conditions, thus simulating hypoxia and reoxygenation. The human umbilical venous endothelial cells were incubated with a degassed buffer (oxygen content: 0-0.5%) for either 3 h or 24 h, followed by a 60 min incubation with oxygen-perfused buffer (oxygen content: 100%). Three hours of hypoxia led to a slight decrease in the ATP and creatine phosphate content (-16% +/- 5%), while a pronounced decrease of high energy phosphates (-54% +/- 4%) was observed after 24 h of hypoxia. Reoxygenating the cells after 3 h of hypoxia led to restoration of the content of high energy phosphates, while reoxygenation after 24 h resulted in a strong decrease (-66% +/- 4%). The prostaglandin I2 release during the first 3 h of hypoxia exceeded the release in the following 21 h. In all cases, reoxygenation increased the prostaglandin I2 release. Under normoxic conditions the ratio between oxidised glutathione and reduced glutathione shifted from 1:100 to 1:4.5 after 3 h of hypoxia. The content of lipid peroxidation products was almost unaffected during hypoxia, whereas reoxygenation resulted in a pronounced increase (+380% +/- 60%). The results of this in vitro study suggest that relatively long periods of hypoxia lead to a deficiency of high energy phosphates in the cell. Reoxygenation leads to the formation of oxygen-derived radicals, irrespectively of a prior hypoxia.

Adenosine Triphosphate↗
PubMed1994

[Coping with anger by cardiovascular patients].

Patients with essential hypertension and coronary heart disease were compared to a healthy and clinical control group an the recently developed Müller-Anger-Coping Questionnaire (MAQ). The inventory measures the factors "Spontaneous Behavior" (f1), "Controlled Affect" (f2), "Guilt" (f3) and "Social Inhibition" (f4) as a trait. The patients, suffering from essential hypertension, in comparison to the healthy control group, showed significant differences on factors 2 to 4, indicating, that they are expressing anger to a lesser degree and that they are more likely to exhibit an anger-in/guilt coping style. The same was true for patients suffering from coronary heart disease with respect to factors 2 and 4. With respect to "Guilt" coronary heart disease patients showed a clear trend for more feelings of guilt after anger expression, as compared to the healthy control group. None of the groups showed significant differences on expressing anger-in an aggressive manner (factor 1). These results provide further evidence, that patients with cardiovascular disorders have a clear tendency to show anger to a lesser degree in an socially assertive manner and to suppress anger. If anger is expressed by these patients, they tend to feel guilty. Implications of the findings are discussed.

Adaptation, Psychological↗
PubMed1992

Decreased tissue reaction to bioprosthetic heart valve material after L-glutamic acid treatment. A morphological study.

Degenerative alterations of two different glutaraldehyde (GA)-fixed bioprosthetic heart valve materials were investigated in subcutaneous rat implants: Bovine pericardium, prepared according to clinically used bioprosthetic heart valve material (BHV) was compared to alternatively preserved pericardium (APHV), which was fixed in GA and treated with L-glutamic acid. Following 63 days of subcutaneous implantation, calcification of APHV implants was significantly lower as compared to BHV implants (13 +/- 6 versus 158 +/- 18 micrograms Ca/mg dry weight tissue; p less than 0.05). In BHV implants ultrastructural investigations showed nucleation of plate-shaped hydroxyapatite crystals at the surface of collagen fibrils and in remnants of connective tissue cells; no signs of calcification could be detected in APHV implants. The time-course of the inflammatory reaction was determined by quantification of immunohistochemical stained mononuclear host-cells invading the implants. In both preparation groups inflammatory reaction reached maximum 42 days after implantation. However, infiltration rate of inflammatory cells was markedly decreased in APHVs as compared to BHVs (p less than 0.05).

Animals↗
PubMed1992

Neopterin release from human endothelial cells is triggered by interferon-gamma.

Human umbilical vein endothelial cells (HUVEC) were investigated for their ability to produce neopterin, a biochemical marker for an activated immune system. Interferon-gamma (IFN-gamma), IL-1 alpha, IL-2, IL-6, tumour necrosis factor-alpha, granulocyte/macrophage colony stimulating factor, phytohaemagglutinin and concanavalin A were used to stimulate HUVEC. While IFN-gamma induced neopterin release from HUVEC in a time- and dose-dependent manner, all the other cytokines used had no effect on neopterin production. High neopterin levels are found in patients with rejection episodes or infections. Our results suggest that not only monocytes and macrophages, which are known to synthesize neopterin, but also endothelial cells are responsible for these high serum neopterin levels.

Biopterins↗
PubMed1992

Improved biocompatibility of bioprosthetic heart valves by L-glutamic acid treatment.

Treatment of glutaraldehyde-fixed pericardium with L-glutamic acid and storage in bacteriostatic preservatives (paraben) stably antagonizes free, reactive aldehyde groups within the fixed bioprosthetic heart valve tissue. In 63-day subcutaneous implants in rats, the calcification rate of this treatment (13.3 +/- 2 mg calcium/g wt tissue) was markedly reduced as compared to conventionally treated tissue (169 +/- 24 mg/g; p less than 0.05). To test the influence of tissue-released toxic aldehydes on spontaneous endothelial cell ingrowth in vivo, vascular grafts (8-cm long, 6-mm diameter) from fixed pericardium treated with L-glutamic acid were interposed into the carotid arteries in ten sheep. They were compared to grafts from conventionally treated pericardium implanted at the contralateral side. Following 3 months of implantation, planimetry revealed 49% +/- 20% of the surface of conventionally preserved pericardium to be covered with red thrombus, but only 12% +/- 5% in L-glutamic acid treated pericardium (p less than 0.05). The ultrastructural findings of a closed endothelial cell layer on the graft surface reveals the new technique to be a promising approach towards increased biocompatibility of aldehyde-fixed bioprosthetic heart valves.

Animals↗
PubMed1992

Endothelial cell lining of bioprosthetic heart valve material.

In this in vitro study, the growth properties of cultured endothelial cells on conventionally treated pericardial valve material were measured. These data were compared to endothelial cell proliferation on an alternatively treated valve material. This alternative preservation procedure was developed in order to bind free, residual glutaraldehyde in the valve tissue by reaction with L-glutamic acid. In order to optimize endothelial cell attachment and proliferation, fibronectin and fibrillar collagen type I were tested as surface precoating substances. Cell viability of the seeded cells was evaluated by means of proliferation kinetics, antithrombotic activity, and morphological appearance. Endothelial cell death occurred within the first 2 days after seeding on conventionally treated valve tissue, independent of the type of precoating. On alternatively treated tissue, regular endothelial cell proliferation was observed. Precoating with fibrillar collagen markedly increased endothelial cell attachment and proliferation as compared to fibronectin. Maintenance of antithrombotic activity of the seeded cells was proven by regular release of prostacyclin.

Animals↗
PubMed1992

Endothelial cell lining of bioprosthetic heart valve materials.

To investigate the conditions for endothelial cell lining of glutaraldehyde-treated bioprosthetic heart valves, we examined in vitro the growth properties of endothelial cells on clinically used pericardial valve material and on glutaraldehyde-fixed pericardium treated with L-glutamic acid. To improve endothelial cell attachment to the valvular surface, we precoated both materials either with fibronectin or with fibrillar collagen (95% type I, 5% type III). Toxicity of glutaraldehyde, released from clinically used valve material, caused endothelial cell death, independent of the type of precoating. Treatment of the valve material with L-glutamic acid resulted in regular endothelial cell proliferation. We found that collagenous precoating, compared with fibronectin precoating, markedly enhanced endothelial cell proliferation and attachment (p less than 0.05). Maintenance of antithrombogenic potency of the seeded cells on L-glutamic acid-treated valve material was proved by regular release of prostacyclin. We conclude that bioprosthetic heart valve materials can be lined with endothelial cells if toxic glutaraldehyde released from the bioprostheses is eliminated.

Animals↗
PubMed1992

Aprotinin decreases release of 6-keto-prostaglandin F1 alpha and increases release of thromboxane B2 in cultured human umbilical vein endothelial cells.

Use of the proteinase inhibitor aprotinin significantly improves hemostasis and reduces bleeding after operations in which extracorporeal circulation is used. The mechanism of action, however, has been only partially clarified. In this work we investigated whether aprotinin influenced the production and release of the eicosanoids prostacyclin, measured as the stable metabolite 6-keto-prostaglandin F1 alpha, and thromboxane A2, measured as the stable metabolite thromboxane B2, from endothelial cells. Human umbilical vein endothelial cells were incubated with different concentrations of aprotinin (5.5, 20, 55, and 100 mumol/L). The levels of 6-keto-prostaglandin F1 alpha and thromboxane B2 were measured at baseline and after thrombin stimulation. A concentration-dependent effect of aprotinin on 6-keto-prostaglandin F1 alpha synthesis was demonstrated. After incubation with 100 mumol/L of aprotinin, a 90% reduction in 6-keto-prostaglandin F1 alpha production was seen (31.69 versus 307.44 picograms per million cells; p less than 0.001). Conversely, thromboxane B2 production showed a 345% increase after incubation with aprotinin (287.80 versus 83.82 picograms per million cells; p less than 0.0001). Since 6-keto-prostaglandin F1 alpha inhibits and thromboxane B2 strongly enhances platelet aggregation, it appears that one mechanism of the clinically observed effectiveness of aprotinin lies in the altered ratio of 6-keto-prostaglandin F1 alpha: thromboxane B2 in endothelial cells, which leads to enhanced platelet aggregation and improved vessel sealing.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Serum lipid peroxide levels in the course of coronary by-pass surgery.

Reperfusion of the ischemic myocardium is associated with the extension of already existing injury. Investigation of the reperfused myocardium under different conditions revealed ultrastructural changes as well as functional disturbances which were identified as free radical-mediated damage. Free radical scavengers and antioxidant agents have been shown to reduce the size of the infarct, in which a temporary regional ischemia was followed by reperfusion. Elaborately designed in vitro and animal models strongly suggest that reperfusion injury might be of clinical significance in operations involving extracorporeal circulation, as in coronary by-pass surgery. However, there is limited information on the relationship between reperfusion injury and subsequent clinical conditions. In our study, we determined lipid peroxide concentrations in timed serum samples of patients who had undergone coronary by-pass surgery. Preoperative lipid peroxide concentrations were 2.50 +/- 0.50 mumol/l. This value increased to 3.30 +/- 1.00 mumol/l after six hours and showed a second increase to 4.20 +/- 0.80 mumol/l 48 hours after the onset of reperfusion. These results suggest that postoperative increases in lipid peroxide concentrations can be of multifactorial origin and may be an indication of reperfusion injury to the myocardium. Further studies are under way to elucidate the relevance of this increase in different groups and clinical conditions.

Aged↗
PubMed1992

Glutaraldehyde affects biocompatibility of bioprosthetic heart valves.

A marked release of glutaraldehyde from commercially available pericardial bioprosthetic heart valve (BHV) material in washing solutions was found by high performance liquid chromatography (up to 1.8 ppm of glutaraldehyde per gram of dry tissue). In vitro endothelial cell proliferation rate was impaired dose-dependently in the presence of increasing glutaraldehyde concentrations of the cultivation medium (r = 0.9; p less than 0.05). Cultivation of endothelial cells was impossible on the surface of commercially available BHV material, but successful and uninhibited when toxic glutaraldehyde ligands of the BHV material were antagonized by treatment with L-glutamic acid.

Animals↗
PubMed1991

Regulation of eicosanoid release in human umbilical endothelial cells.

The concentration dependent influence of adenine nucleotides, thrombin and ionophore A 23187 on eicosanoid-production of human endothelial cells was investigated. The prostaglandin I2 (PGI2)-and thromboxane A2 (TXA2)-release were highest at concentrations of 1 mmol/l and 4 mmol/l adenine nucleotides, respectively. TXA2-release decreased at higher concentrations. Ionophore-induced eicosanoid-formation reached its maximum at 15 mumol/l for both PGI2 and TXA2. Thrombin stimulation resulted in a bell shaped concentration dependency, whereby most TXA2 was released at a concentration of 1 U/ml and most PGI2 at 5 U/ml. Intracellular cAMP showed significant (p less than 0.01) increases stimulating cells with ADP- and ATP-concentrations higher than 500 mumol/l, whereas ionophore and thrombin did hardly affect cAMP levels.

6-Ketoprostaglandin F1 alpha↗