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U Müller-Werdan

Publications and source records attributed to U Müller-Werdan.

At least 19 recordsLinked to original sources
PubMed2005

[Reversible autonomic dysfunction in a young woman with septic multiple organ dysfunction syndrome].

HISTORY: A 24-year-old woman was admitted for treatment of a meningococcal infection accompanied by fulminant autonomic dysfunction. INVESTIGATIONS: Laboratory tests indicated acute renal failure and disseminated intravascular coagulopathy (creatinine 183 mmol, D-dimer 1.52 mg/l). The initial central venous oxygen saturation was 60-65%. The diagnosis of severe septic shock was supported by a high procalcitonin level of 66.7 ng/ml, CRP of 79.8 mg/l, and a WBC count of 12.2 Gpt/l. TREATMENT AND COURSE: Treatment of sepsis with antibiotics (ciprofloxacin, penicillin G, ceftriaxon and erythromycin in standard dosages), activated protein-C, hydrocortisone and GMA-embedded immunoglobulin led to complete cure and restoration of normal autonomic function. CONCLUSIONS: This case shows that even in multiple organ dysfunction syndrome autonomic dysfunction can occur which is improved by adequate treatment.

Adult↗
PubMed2004

[Catecholamine therapy in cardiogenic shock: helpful, useless or dangerous?].

Cardiogenic shock is characterized by inadequate organ and tissue perfusion, due to cardiac dysfunction, predominantly following acute myocardial infarction. Mortality rates for patients with cardiogenic shock remain high, ranging from 50-70 % despite effective therapy. Rapid diagnostics, aggressive therapeutic approach (invasive or surgical revascularisation) and pharmacological support are currently used to improve the clinical outcome and survival. In the first line commonly sympathomimetics like dopamine, dobutamine, epinephrine and norepinephrine are used for the pharmacological treatment. They have a high affinity for alpha- and beta adrenergic receptors, leading to a positive inotropic cardiac function, an increase in heart rate, oxygen enhanced demand, and an increase in vasoconstriction. However, there are also some disadvantages in the use of sympathomimetics in patients with cardiogenic shock. Clearly, metabolic acidosis due to the increased oxygen demand can be observed. Vasoconstriction induced by sympathomimetics can lead to perfusion mismatch or even deficit within the microcirculation. Additionally, in some studies which give evidence that the use of sympathomimetics can directly lead to enhanced systemic inflammatory response due to an increased IL-6 expression. However, sympathomimetics are still first line therapeutics for treatment of cardiogenic shock -- with respect to dosage and duration of treatment.

Age Factors↗
PubMed2003

[End-organ damage in inflammation and sepsis].

Inflammatory components form part of the pathogenesis of infectious, but also non-infectious diseases. One of the most important revelations of the last decades was the finding of an activation of the natural immune response in numerous physiological and pathophysiological processes despite the absence of an infectious agent. Even physical exercise or psychical stress may evoke an inflammatory response. Substantial insight has been gained in the recent decades into the molecular mechanisms of cellular and organ dysfunction by the impact of mediators with inflammatory potential. Validated score systems allow a precise detection and quantification of organ dysfunctions in inflammation and sepsis. In contrast therapy of organ damage in severe septic and non-septic inflammatory processes presently is mainly still based on supportive therapeutic measures.

Humans↗
PubMed2002

Separation and identification of human heart proteins.

Heart failure is not a uniform disease entity, but a syndrome with various causes, including hypertension, ischemia and congenital heart disease, cardiomyopathy, myocarditis and intoxication. During the recent years a number of molecular and cellular alterations have been identified in the diseased heart, but a direct causative link between these changes and functional impairment, medical responsiveness, progression of the disease and the patients' outcome remains to be established. After an accumulation of large amounts of DNA sequence data in genomic projects, scientists have now turned their attention to the central executors of all programs of life, the proteins. In complementation of the genomic initiatives, proteomics based approaches have lined up not only for large-scale identification of proteins and their post-translational modifications, but also to study the function of protein complexes, protein-protein interactions and regulatory and signalling cascades in the cellular network. In concert with genomic data functional proteomics will hold the key for a better understanding and therapeutical management of cardiovascular diseases in the future.

Humans↗
PubMed2001

[Definition of shock types].

Definitions of shock types. Hypovolaemic shock is a state of insufficient perfusion of vital organs with consecutive imbalance of oxygen supply and demand due to an intravascular volume deficiency with critically impaired cardiac preload. Subtypes are haemorrhagic shock, hypovolaemic shock in the narrow sense, traumatic-haemorrhagic shock and traumatic-hypovolaemic shock. Cardiac shock is caused by a primary critical cardiac pump failure with consecutive inadequate oxygen supply of the organism. Anaphylactic shock is an acute failure of blood volume distribution (distributive shock) and caused by IgE-dependent, type-I-allergic, classical hypersensibility, or a physically, chemically, or osmotically induced IgE-independent anaphylactoid hypersensibility. The septic shock is a sepsis-induced distribution failure of the circulating blood volume in the sense of a distributive shock. The neurogenic shock is a distributive shock induced by generalized and extensive vasodilatation with consecutive hypovolaemia due to an imbalance of sympathetic and parasympathetic regulation of vascular smooth muscles.

Anaphylaxis↗
PubMed2001

Autonomic dysfunction in the ICU patient.

The sympathetic-parasympathetic balance may be altered in critically ill patients. Assessment of autonomic function provides information concerning prognosis, pathogenesis, and treatment strategies in ICU-relevant disorders. Proven tools are heart rate variability, baroreflex sensitivity, and, with limitations, cardiac chemoreflex sensitivity. New nonlinear methods are being evaluated that may predict risk more precisely in critically ill patients. This article summarizes application of these tools in the ICU. In addition, a model is introduced for investigating the impaired autonomic function in multiple organ dysfunction syndrome and sepsis, integrating extrinsic mechanisms and factors that are intrinsic to the cardiac tissue. By this combined approach, the authors hope to gain insight into the pathogenesis of multiple organ dysfunction syndrome. New pathophysiologic concepts are needed for the development of treatment strategies for this life-threatening disease.

Autonomic Nervous System↗
PubMed2000

[Anaphylactic shock].

IgE-dependent and IgE-independent hypersensitivity reactions, the latter due to physical, chemical or hyperosmolar stimuli, may evolve as anaphylaxis or an anaphylactoid reaction, by an escalating release of mediators from mast cells and basophils. Without immediate treatment, anaphylaxis goes along with substantial morbidity (shock, multiple organ failure) and mortality; within minutes this explosive clinical response can be fatal. The severity of anaphylactic/anaphylactoid reactions is graded from stages 0 to IV in order to guide the management of this disease, stage III corresponding to anaphylactic shock. Severe anaphylactic reactions may take a progressive course despite adequate therapy; even in the case of an initial favourable response to treatment measures life-threatening symptoms may recur; there may be late-phase reactions 6 to 12 hours after the initial reaction. For the initial emergency management a differentiation between IgE-mediated and IgE-independent anaphylactoid reactions is not required. These are the pertinent principles of therapy in hypotensive and hypoxic patients: removal of the likely noxious agent at the site of introduction, provision of a patent airway, 100% oxygen supplementation, intravenous fluid therapy and pharmacological support with catecholamines. After primary care the monitoring and therapy of the patient with anaphylactic shock has to be continued on the intensive care unit. Guidelines for management of acute anaphylaxis referring to both the stage of disease including shock and the main clinical manifestation (cutaneous, pulmonary, cardiovascular) have been established by a German interdisciplinary consensus conference and were published in 1994; consensus guidelines for emergency medical treatment have been communicated by the ILCOR (1997) and the Project Team of the Resuscitation Council (UK) (1999).

Acute Disease↗
PubMed2000

Heterogeneity of cardiac rat and human elongation factor 2.

Elongation factor 2 (EF-2) catalyses the last step of the elongation cycle, translocation, in the course of protein biosynthesis. A system for analyzing post-translational modifications of EF-2, which is a single polypeptide of 857 amino acids, is reported and its application to cytosolic extracts of cultured neonatal rat heart myocytes, neonatal and adult rat cardiac tissue, and extracts of human left ventricular myocardium is described. Comparing different pH ranges in immobilized pH gradient-isoelectric focusing (IPG-IEF), a range of pH 3 - 10 and 4 - 9 resulted in a highly defined and reproducible resolution of six different EF-2 variants of all extracts in the first dimension. These six variants were detected by the "imaging plate" (phosphor radiation image sensor) after specific labeling with Pseudomonas exotoxin A catalyzed [32P]ADP-ribosylation. This finding could be confirmed in Western blot analysis with a specific polyclonal rabbit antibody. Using two-dimensional polyacrylamide gel electrophoresis (2-D-PAGE), five to six EF-2 variants could be demonstrated in all extracts. By application of a second IPG indicator strip to the 2-D gel, they could be aligned with corresponding spots in a silver-stained 2-D separation of human myocardial tissue, revealing that the EF-2 variants belong to the group of low-abundance proteins.

Adenosine Diphosphate Ribose↗
PubMed2000

Immune modulation by catecholamines--a potential mechanism of cytokine release in heart failure?

Cytokine blood levels are found to be moderately elevated in chronic heart failure, as a function of severity of disease. The source of these cytokines and the trigger mechanisms stimulating cytokine release are a matter of intense research. Potential players include bacterial endotoxin from intestinal translocation, a neurohumoral dysbalance with an enhanced sympathetic tone or an overspill of cytokines from the failing heart itself. We present arguments in favor of a direct link between the chronically enhanced sympathetic tone in heart failure and the clinically overt activation of the immune system, particularly interleukin 6 release.

Catecholamines↗
PubMed2000

Improved outcome of APACHE II score-defined escalating systemic inflammatory response syndrome in patients post cardiac surgery in 1996 compared to 1988-1990: the ESSICS-study pilot project.

OBJECTIVE: Cardiac surgery using extracorporeal circulation leads to the release of cytokines and subsequently to a systemic inflammatory response syndrome, which is thought to be a negative prognostic factor for patients' outcome. A stratification for the risk of an escalating systemic inflammatory response syndrome had been achieved in a monocenter study carried out in 1988-1990, using APACHE II scoring on the morning of the 1st postoperative day. We now re-evaluated this concept prospectively in three independent centers. METHODS: The APACHE II based risk stratification was put to test in three independent heart surgery centers in the period from June to December 1996. Nine hundred and forty-five patients after elective cardiac surgery (excluding heart transplantation) with the assistance of the cardiopulmonary bypass were prospectively monitored. RESULTS: We found an increase in mortality with higher APACHE II score values determined on the 1st postoperative day. The mortality rose to nearly 50% with an APACHE II score of > or = 28. Patients at high risk for the development of a systemic inflammatory response syndrome (APACHE II score > or = 24) significantly differed from patients at lower risk (APACHE II score < 19) in the duration of mechanical ventilation and extracorporeal circulation, age and New York Heart Association (NYHA) classification (P < 0.05). CONCLUSION: The APACHE II score determined on the morning of the 1st postoperative day helps identifying the subgroup of patients with escalating systemic inflammatory response syndrome. Comparison with the data obtained in the years 1988-1990, suggests a better prognosis in the current trial for patients at high risk with a similar degree of escalating systemic inflammatory response syndrome.

APACHE↗
PubMed1999

Impaired energy metabolism in hearts of septic baboons: diminished activities of Complex I and Complex II of the mitochondrial respiratory chain.

Recent findings support the view that the bioenergetic part of septic organ failure is not caused by insufficient supply of oxygen but by disturbances of the mitochondrial function. Therefore, the aim of the present study was to investigate key enzymes of energy metabolism in septic hearts to answer the question whether or not impairment of mitochondrial or glycolytic enzymes occur under these conditions. For this purpose the well established model of septic baboons was used. Baboons under general anesthesia were made septic by infusion of Escherichia coli. Single challenge with infusion of high amounts of bacteria was compared with a multiple challenge protocol (less bacteria infused). Some animals obtained no E. coli (sham). The hearts of the baboons were removed after 72 h (survival: yes) or after death (survival: no) of the animals, frozen in liquid nitrogen, and stored at -80 degrees C until spectrophotometrical measurement of nine mitochondrial and glycolytic enzymes. A reduction of the activity of NADH:cytochrome-c-reductase (Complex I + III) to 67% and succinate:cytochrome-c-reductase (Complex II + III) to 45% was found in the hearts of surviving animals after infusion of high amounts of bacteria. After multiple challenge with lesser amounts of bacteria, no significant changes in enzyme activity were detectable. After lethal septic shock, activities of Complex I + III (12%) and Complex II + III (13%) as well as of phosphofructokinase (16%) were found to be strongly diminished. Decylubiquinol:cytochrome-c-reductase (Complex III, 59%), cytochrome-c-oxidase (51%), succinate dehydrogenase (60%), glucosephosphate isomerase (61%), lactate dehydrogenase (61%), and citrate synthase (120%) were less or unaffected. Similar but less pronounced effects were found after infusion of lesser amounts of bacteria. By means of inhibitor titrations of succinate: cytochrome-c-reductase, it was shown that the loss of activity is not caused by Complex III but by disturbances in Complex II. It is concluded that E. coli-induced sepsis causes decreased activities of Complex I and Complex II in baboon heart mitochondria in a dose-dependent manner.

Animals↗