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Biomedical subjects

K Werdan

Publications and source records attributed to K Werdan.

At least 19 recordsLinked to original sources
PubMed2001

Assessment of chemoreflex sensitivity in free breathing young subjects by correction for respiratory influence.

BACKGROUND: The assessment of autonomic function is an important tool for risk stratification in critically ill patients. Peripheral cardiac chemoreflex sensitivity has been considered a marker for increased risk of sudden cardiac death. In normals, the evaluation of peripheral cardiac chemoreflex sensitivity is performed under controlled breathing conditions during inhalation of hypoxic gas. Since this is poorly tolerated by patients, they are commonly studied under hyperoxic conditions, which are not physiological. METHODS: We studied 20 healthy volunteers who underwent free and controlled breathing of a hypoxic gas mixture (10% O2 in N2) over 5 min. Values of peripheral cardiac chemoreflex sensitivity, corrected for respiratory influence, were compared with the results obtained experimentally under controlled breathing conditions in the same subjects. RESULTS: We found a substantial difference between values obtained during free and controlled breathing (3.64 +/- 0.81 vs. 1.53 +/- 0.32 ms/mmHg, respectively; P < 0.05). After application of a respiratory correction, described and validated in this article, no significant difference was seen for these values (0.89 +/-0.91 vs. 1.53 +/- 0.32 ms/mmHg, P = 0.46). CONCLUSIONS: This approach allows the evaluation of peripheral cardiac chemoreflex sensitivity in free breathing subjects. This correction could improve the assessment of cardiac chemoreflex sensitivity in patients with cardiorespiratory disorders, who find it difficult to control their breathing according to an experimental protocol.

Adult↗
PubMed2001

Pathophysiology of septic shock and multiple organ dysfunction syndrome and various therapeutic approaches with special emphasis on immunoglobulins.

The pathophysiology of sepsis and septic shock is dominated by an imbalance of pro- and antiinflammatory mediators produced by toxin-activated inflammatory cells. Both the overshooting of proinflammatory mediators as well as the development of immune paralysis are deleterious to the patient. Available therapeutic approaches with monoclonal antibodies and antagonists targeted against toxins and mediators have focused mainly on inhibition of overshooting proinflammation: the results, however, have been disappointing. Due to these disappointing results of specific antiinflammatory regimens, adjuvant treatment of sepsis and septic shock with intravenous immunoglobulins (IVIgs) has regained interest although this indication has at best been validated in part. Likely beneficial mechanisms of action may include the improvement of serum bactericidal activity due to neutralizing and opsonizing IgG and IgM antibodies as well as stimulation of phagocytosis and neutralization of bacterial endo- and exotoxins; another attractive mode of action may represent Ig-mediated modification and specific suppression of proinflammatory cytokine release from endotoxin- and superantigen-activated blood cells. For the total group of patients with sepsis and septic shock, a reduction in mortality by IVIg could not be documented; however, in the SBITS study with 653 patients included, a moderate improvement in sepsis morbidity and multiple organ dysfunction syndrome was demonstrated. In defined sepsis sub-groups, a reduction in mortality by IVIg has been seen in each small, not yet confirmed trial. Thus, IVIg is not a magic bullet of sepsis treatment, but it may reduce morbidity and thereby may be useful in the therapeutic mosaic of sepsis treatment.

Animals↗
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↗
PubMed2000

Cerebrovascular reactivity is impaired in patients with cardiac failure.

AIMS: We undertook this study to evaluate potential changes in cerebral vasoreactivity in patients with cardiac failure and their consequent dependence upon cardiac functional variables. METHODS AND RESULTS: A total of 50 patients with various degrees of heart failure, 20 age-matched controls and 20 normal controls were examined. Cerebrovascular reactivity was examined with the carbon dioxide technique. Mean flow velocities of both middle cerebral arteries as well as end-tidal carbon dioxide partial pressure were continuously registered. Normal controls were examined on two different occasions, to evaluate the technique's reproducibility. Cerebrovascular reactivity was significantly reduced in all examined patients as compared to controls, and in NYHA IV as compared to NYHA II and III patients. A significant relationship between cerebrovascular reactivity and left ventricular ejection fraction was evident. Reproducibility of the technique was satisfactory. CONCLUSION: Our study provided evidence of significantly reduced cerebrovascular reactivity in patients with cardiac failure, which was significantly related to the NYHA grade and the left ventricular ejection fraction.

Blood Flow Velocity↗
PubMed1999

The overall concept: immunoglobulins as adjuvants for mediastinitis--does it make sense?

Supportive intravenous immunoglobulin (ivIg) treatment may reduce the incidence and severity of infections in a well-defined group of patients in intensive care, including those who have had cardiac surgery. Sternal wound infections and mediastinitis after cardiac surgery are to be investigated in the ATMI study with Pentaglobin. In this article I focus on optimising ivIg dosage, on likely mechanisms, on reasons why ivIg might improve a primarily gram-positive infection, and on the use of serial scoring as an endpoint in a trial of immunoglobulin.

Cardiac Surgical Procedures↗
PubMed1999

Hemofiltrate from patients with severe sepsis and depressed left ventricular contractility contains cardiotoxic compounds.

Myocardial dysfunction due to sepsis is common in patients with multiple organ dysfunction syndrome and is believed to be produced by inflammatory mediators. Some of these mediators may be eliminated by continuous hemofiltration, which is a standard procedure in an ICU for renal replacement therapy. This study was designed to directly compare the effects of ultrafiltrates from patients with sepsis (UFs) with ultrafiltrates from healthy volunteers (UFh) in well-characterized cardiomyocyte culture systems. Isovolemic hemofiltration (filtration rate: 2 L/h, polyamide membrane) was performed during 12 hours in 5 patients with severe sepsis (Elebute Score >20) and simultaneously reduced left ventricular contractility (left ventricular stroke work index [LVSWI] <30 g m/m2) and in 5 healthy volunteers. Inflammatory mediator concentrations (interleukin [IL]-1beta, IL-6, IL-8, tumor necrosis factor [TNF] alpha, C3a, and C5a) were measured in plasma and ultrafiltrate samples taken shortly after the beginning of the hemofiltration procedure. Cell culture experiments were done comparing UFs with UFh by using spontaneously beating or electrically driven neonatal rat cardiomyocyte cultures. UFs contained significantly higher amounts of IL-1, IL-8, and C3a when compared to UFh. Simultaneously, UFs induced a decrease in the contraction frequency of electrically-stimulated cardiomyocytes, whereas UFh had no effect. The cardiotoxic effect could be reversed by the addition of a high concentration (2.4 mM) of Ca++. Hemofiltration did not alter parameters of cardiac performance during 12 hours in patients with sepsis. UFs induced significant cardiotoxic effects in rat cardiomyocytes, whereas UFh showed no cardiotoxicity. Contact of blood with the hemofiltration membrane did not induce activation of cardiotoxic mediators. Significantly higher filtration rates may be required to improve left ventricular contractility in patients with sepsis by hemofiltration.

Adult↗
PubMed1999

Supplemental immune globulins in sepsis.

Intravenous immune globulins are widely used as supplemental treatment of sepsis, septic shock and systemic inflammation in the critically ill, although this indication has at best been validated in part. Likely beneficial mechanisms of action may include the improvement of serum bactericidal activity due to neutralizing and opsonizing immunoglobulin (Ig)G- and IgM-antibodies, as well as stimulation of phagocytosis and neutralization of bacterial endo- and exotoxins; another attractive mode of action may represent immune globulin-mediated modification and specific suppression of proinflammatory cytokine release from endotoxin- and superantigen-activated blood cells. For the "entire group of patients with sepsis and septic shock" a reduction in mortality by intravenous immune globulin could not be documented; however, in the score-based immunoglobulin in sepsis (SBITS)-study with 653 patients included, a moderate improvement in sepsis morbidity and multiple organ dysfunction syndrome was demonstrated. In defined sepsis subgroups, a reduction in mortality by intravenous immune globulin has been seen in individual small, not yet confirmed trials. Finally, the incidence of some severe infections in well characterized "patients at risk" and "operations at risk" is reduced by intravenous immune globulin prophylaxis. Thus, intravenous immune globulin is not a "magic bullet"of sepsis treatment, but it may reduce morbidity and thereby represent a useful piece of stone in the therapeutic mosaic of sepsis treatment.

Controlled Clinical Trials as Topic↗
PubMed1999

Reduction of circulating cholesterol and apolipoprotein levels during sepsis.

Sepsis with multiple organ failure is frequently associated with a substantial decrease of cholesterol levels. This decrease of cholesterol is strongly associated with mortality suggesting a direct relation between inflammatory conditions and altered cholesterol homeostasis. The host response during sepsis is mediated by cytokines and growth factors, which are capable of influencing lipid metabolism. Conversely lipoproteins are also capable of modulating cytokine production during the inflammatory response. Therefore the decrease in circulating cholesterol levels seems to play a crucial role in the pathophysiology of sepsis. In this review the interaction between cytokines and lipid metabolism and its clinical consequences will be discussed.

Animals↗