Evaluation of definitions of sepsis.
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
K Werdan
Publications and source records attributed to K Werdan.
Changes in skeletal muscle pO2 after administration of anti-TNF alpha-antibody in patients with severe sepsis: comparison to interleukin-6 serum levels, APACHE II, and Elebute scores.
In 20 patients with severe sepsis, skeletal muscle pO2 was continuously measured in order to assess whether a decrease of skeletal muscle pO2 was accompanied by an improvement of sepsis after repeated administration of F(ab')2 fragments of a murine anti-TNF alpha-antibody. Abnormally high skeletal muscle pO2 decreased from 43.5 +/- 10.9 mmHg (day 0) to 36.4 +/- 10.1 mmHg within 24 h after the first administration of anti-TNF alpha-antibody (day 1, p = .006, n = 20) and remained at 34.6 +/- 7.7 mmHg thereafter (mean day 2-7, p = .004). The decrease of skeletal muscle pO2 within 24 h exceeded 5 mmHg (-7 to -19 mmHg) in 11 patients in contrast to nine patients (-4 to +4 mmHg). Only in the patients showing a decrease of skeletal muscle pO2 did sepsis improve as determined by Elebute score, APACHE II score, and interleukin-6 serum levels. The change of skeletal muscle pO2 within 24 h was associated with a change of interleukin-6 serum levels within 24 h (r = .5, n = 20), with a change of Elebute score (r = .7, n = 20) and of APACHE II score (r = .62). These data suggest that a decrease of skeletal muscle pO2 might be an early indicator of improvement of sepsis after administration of anti-TNF alpha-antibodies.
Adult↗
Pseudomonas sepsis does not cause more severe cardiovascular dysfunction in patients than non-Pseudomonas sepsis.
To evaluate the clinical relevance of the experimental findings of a more severe cardiac depression in Pseudomonas (P.) than in non-P. sepsis, we retrospectively compared the hemodynamic data in 26 patients with P. sepsis (20 cases, single pathogen; six cases, more positive cultures with P. than with non-P. species), and 102 with non-P. sepsis. As in other studies, the left ventricular stroke work index (LVSWI) was used to assess cardiac performance. The two groups (all numbers are means) had a similar disease and sepsis severity profile (P. vs. non-P: septic shock, 81% vs. 87%; APACHE II scores, 29.1 vs. 29.2; Elebute sepsis scores, 18.1 vs. 18.1; mortality, 58% vs. 62%). Preload (pulmonary capillary wedge pressure 15.0 vs. 16.3 mm Hg) and systemic vascular resistance (588 vs 572 dyn.cm-5.sec) were comparable. Cardiac performance displayed no significant difference (LVSWI, 42.8 vs. 38.3 g.m/m2), a result reproduced in the subgroups with culture-proven bacteremia, with or without preexisting cardiovascular disease or septic shock. Thus, our data suggest that there is no difference in the degree of cardiovascular dysfunction in patients with Pseudomonas compared to non-Pseudomonas sepsis of otherwise equivalent disease severity.
Cardiovascular System↗
Preformed natural antibodies: their impact on beating neonatal rat cardiomyocytes.
Explore the source record for details and available documents.
Animals↗
Desensitization of rat cardiomyocyte adenylyl cyclase stimulation by plasma of noradrenaline-treated patients with septic shock.
The purpose of this study was to test the possibility that the mechanisms of catecholamine-induced desensitization of cardiac beta-adrenoceptor stimulation are modified in septic shock. Exposure of neonatal rat cardiomyocytes for 48 hr to plasma of noradrenaline-treated patients with septic shock led to a down-regulation of beta-adrenoceptors by 35%, an increase in the level of inhibitory G protein alpha-subunits by 60%, and a decrease in isoproterenol-stimulated adenylyl cyclase activity by 50% in membranes prepared from the rat cardiomyocytes. Similar alterations were observed following pretreatment of the cells with plasma of adrenaline-treated patients with cardiogenic shock. In contrast, exposure of the cardiomyocytes to plasma of intensive care patients without shock, and to plasma of dopamine-treated patients with septic shock did not induce alterations of the cardiomyocyte adenylyl cyclase system. The dosage of the catecholamines had to be increased within the first two days of treatment in the noradrenaline-treated patients, but not in the dopamine-treated patients with septic shock. Thus, this observed tolerance to noradrenaline in the treatment of septic shock may, in part, be due to a desensitization of cardiac beta-adrenoceptor stimulation induced by the beta-adrenoceptor stimulatory effect of noradrenaline.
Adenylyl Cyclases↗
[Continuous measurement of peripheral oxygen availability in skeletal muscle of patients with infection].
In patients with sepsis, a pathologic oxygen uptake supply dependence due to an oxygen extraction defect was suggested to result in tissue hypoxia--a hypothesis which is discussed controversially. In order to determine more directly whether the oxygen transport to tissue was reduced in patients with sepsis, the distribution of skeletal muscle pO2 was measured intermittently by polarographic needle electrodes in 28 patients with sepsis for 7 days. Comparison of intermittent with continuous measurements by pO2 catheters showed a close linear relation (r = 0.88; p < 0.001) and acceptable agreement. Therefore, continuous measurement of skeletal muscle pO2 by pO2 catheters can be used as an estimate of mean skeletal muscle pO2. Neither by intermittent nor by continuous measurements, skeletal muscle hypoxia was detected in patients with sepsis. In contrast, the skeletal muscle pO2 was statistically significantly higher on days with septic state (44.1 +/- 10.3 mm Hg) than on days with intermediate (30.1 +/- 8 mm Hg) and nonseptic (26.8 +/- 5.1 mm Hg) states. From our data we infer that the hypothesis of tissue hypoxia in sepsis must be questioned at least for the skeletal muscle. The increase of skeletal muscle pO2 in sepsis, however, suggested that oxygen utilization within skeletal muscle decreased the more severe the stage of sepsis was. A decreased oxygen utilization within tissue, which may result from a 'downregulation' of oxygen-dependent metabolic pathways, might account for a decreased oxygen extraction of peripheral tissue in sepsis.
Adult↗
[Early immunoglobulin therapy in high risk patients for infection after heart surgery].
The efficacy of early supplemental intravenous immunoglobulin G (ivIgG) treatment was investigated in 41 patients at risk for sepsis following cardiac surgery (APACHE II score > or = 19 on the 1st postoperative day). The ivIgG preparation (Psomaglobin N) was chosen because of its reported high antibody titers and effectiveness in animal models against gram-positive microorganisms, preponderant as infective agents after heart surgery. The control group consisted of a historical cohort of 42 cardiac surgical patients of comparable pretreatment disease and sepsis severity. Following ivIgG therapy on the 1st and 2nd days after surgery, we found a marked improvement in disease severity (fall in APACHE II scores) in contrast to the control patients, especially evident in the high-risk group of patients with an APACHE II score > or = 24 on the 1st postoperative day (n = 26). In this group, ivIgG therapy led to higher (p < 0.05) response rates defined as a score decrease > or = 7 within 4 days (ivIgG-treated patients 54%, controls 19%), and a reduction in mortality (ivIgG-treated patients 46%, controls 76%; p = 0.08). Given the good comparability of the study groups, the results of this trial indicate, despite its nonrandomized design, that early supplemental ivIgG treatment seems to decrease disease severity and probably also improve the prognosis in APACHE II score identified high-risk patients after cardiac surgery.
Aged↗
[Early detection of patients at risk for infection after heart surgery].
Since sepsis is a major cause of mortality after cardiac surgery, early identification of the patients at risk of developing septic complications is of considerable importance. In the present study on 110 patients after elective heart surgery, we, therefore, examined scoring systems as well as various single parameters with regard to an early prediction of septic complications. In a first step, the Elebute score definition for postoperative sepsis in general surgery patients (score > or = 12) could be confirmed for cardiac surgery patients as well. Septic complications, defined as an Elebute score > or = 12 on > or = 2 days, occurred in 16 patients and were associated with a significantly worse prognosis than in non-septic patients (mortality 69 vs. 1%). Consequently, other more practicable parameters were investigated: five additional scores (APACHE II, Goris, HIS, SAPS, SSS) were comparable and superior to plasma levels of elastase and neopterin, haemodynamic data, and clinical parameters in predicting septic complications as early as by the 1st postoperative day. For reasons of practicability and availability, the APACHE II score (predictive values: positive 86%, negative 96%, Youden index 0.73; diagnostic cut off point: > or = 19 on the 1st postoperative day) seemed to be best suited. Therefore, this was further investigated within a consecutive prospective study (independent group of 106 patients) which confirmed an APACHE II score > or = 19 as discriminating criterion (mortality 36 vs 0%). Thus, the APACHE II score may be useful for prospective screening, with the intention to treat, of patients after cardiac surgery who are at risk of postoperative septic complications.
Coronary Artery Bypass↗
Contractile dysfunction of "reperfused" neonatal rat heart cells: a model for studying "myocardial stunning" at the cellular level?
Explore the source record for details and available documents.
Adenine Nucleotides↗
Distinct pathways for beta-adrenoceptor-induced up-regulation of muscarinic acetylcholine receptors and inhibitory G-protein alpha-subunits in chicken cardiomyocytes.
Exposure of cardiomyocytes from chicken embryos for 3 days to the beta-adrenoceptor agonist, isoproterenol, lead to a down-regulation of beta-adrenoceptors by about 70% and to a decrease in isoproterenol-stimulated adenylyl cyclase activity by about 40% (homologous desensitization). In addition, the isoproterenol treatment induced an increase in the level of muscarinic acetylcholine receptors by about 30% and an increase in pertussis toxin-catalyzed ADP-ribosylation of two about 40 kDa proteins, most probably alpha-subunits of the inhibitory G-protein (Gi), by about a factor of two (heterologous desensitization). The purpose of the present study was to characterize the role of beta-adrenoceptor-dependent and -independent mechanisms in heterologous desensitization of adenylyl cyclase. Therefore, the effect of pretreatment with the beta-adrenoceptor antagonist, propranolol, with the partial agonists, celiprolol and xamoterol, and with the beta-adrenoceptor-independent adenylyl cyclase activators, prostaglandin E1 and forskolin, on beta-adrenoceptors, muscarinic acetylcholine receptors and pertussis-toxin-catalyzed ADP-ribosylation of G-protein alpha-subunits was studied. Pretreatment of the cardiomyocytes for 3 days with xamoterol or celiprolol, but not with propranolol, induced a small decrease in beta-adrenoceptor number and in isoproterenol-stimulated adenylyl cyclase activity by about 15-20%. Exposure to prostaglandin E1 and forskolin lead to a more pronounced decrease in beta-adrenoceptor binding and in isoproterenol-mediated adenylyl cyclase stimulation by about 40-60% (heterologous desensitization). An increase in the level of muscarinic acetylcholine receptors, similar to that induced by isoproterenol exposure, was only observed after pretreatment with the partial agonists, celiprolol and xamoterol, but not after pretreatment with the beta-adrenoceptor-independent agonists, prostaglandin E1 and forskolin, nor after pretreatment with propranolol. In contrast, prostaglandin E1 and forskolin exposure lead to a similar increase in pertussis toxin-catalyzed ADP-ribosylation of about 40 kDa G-proteins as isoproterenol exposure whereas treatment with propranolol, celiprolol and xamoterol had no or only a very small effect on pertussis toxin substrates. In summary, the data suggest that, similar as shown for homologous desensitization, cyclic AMP-dependent and -independent mechanisms are also involved in heterologous desensitization of adenylyl cyclase stimulation. The beta-adrenoceptor-induced upregulation of muscarinic acetylcholine receptors and of the alpha-subunits of pertussis toxin-sensitive G-proteins, most probably of Gi, seem to be mediated via distinct pathways.
Adenylyl Cyclases↗
Early prediction of septic complications after cardiac surgery by APACHE II score.
In 110 patients admitted to the intensive care unit after cardiac surgery, daily monitoring [clinical parameters, cardiac index (CI), left ventricular stroke work index (LVSWI) and APACHE II score] was performed in regard to its usefulness in the early prediction of septic complications, a major cause of postoperative mortality. Septic complications (defined as Elebute sepsis score of > or = 12 on > or = 2 days) occurred in 16 patients and were associated with a significantly worse prognosis (mortality 69% vs 1%, P < 0.0001) than was seen in patients without sepsis. While preoperative APACHE II score values did not differentiate between the patients with an uneventful postoperative course and those with septic complications, patients who ultimately developed septic complications had significantly (P < 0.001) higher scores as early as on the evening of the operation day ("day 0"). In addition, in contrast to patients without sepsis, whose scores dropped markedly (P < 0.001) between day 0 and day 1, patients with septic complications invariably had high scores. Compared to single parameters (fever, leucocyte count, CI, LVSWI), the APACHE II score proved to be superior in differentiating between patients who developed sepsis and those who did not. A score of 19 or more on the 1st postoperative day had a sensitivity of 75%, a specificity of 98%, a Youden index of 0.73, a positive predictive value of 86%, and a negative predictive value of 96% in regard to prediction of septic complications.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiac Surgical Procedures↗
Treatment of gram-negative septic shock with an immunoglobulin.
Explore the source record for details and available documents.
Gram-Negative Bacterial Infections↗
[Beta blocker therapy. New aspects--outdated opinions. Interview by G. Riecker].
Explore the source record for details and available documents.
Adrenergic beta-Antagonists↗
Preformed natural antibodies: action on endothelial cells.
Explore the source record for details and available documents.
Animals↗
[Acute septic cardiomyopathy: a manifestation in multi-organ failure in infection?].
Explore the source record for details and available documents.
Heart↗
[Incidence of sudden heart arrest in mitral valve prolapse syndrome].
Among 1500 consecutive forensic autopsy cases 4 cases of sudden cardiac death due to a mitral valve prolapse syndrome could be found. Postmortem diagnosis depends on severe macroskopic changes of the valve leaflets. According to literature there is no increased risk of sudden cardiac death in cases of "silent" mitral valve prolapse. Only in 2%-4% of all cases severe mitral regurgitation or leaflet thickening above 5 mm leads to an increased incidence of sudden cardiac death. The 4 presented cases belong to this subgroup.
Adult↗
Tumor necrosis factor alpha up-regulates Gi alpha and G beta proteins and adenylyl cyclase responsiveness in rat cardiomyocytes.
Treatment of cultured rat cardiomyocytes in serum-free medium for 48 h with recombinant human tumor necrosis factor alpha (TNF alpha) led to a concentration-dependent increase in the level of membrane-inhibitory guanine nucleotide-binding protein (Gi) alpha-subunits and in pertussis toxin-catalyzed [32P]ADP ribosylation of 40 kDa proteins. Both Gi alpha protein subtypes present in rat cardiac myocyte membranes, Gi alpha 40 and Gi alpha 41, were up-regulated by the cytokine, with the maximal increase occurring at 10 U/ml TNF alpha. In contrast to noradrenaline exposure, which causes a similar, but apparently exclusive, increase in alpha i-subunits, treatment with TNF alpha in addition increased the level of membrane G protein beta 36-subunits. Furthermore, while noradrenaline exposure led to a decrease in receptor-dependent and -independent adenylyl cyclase activity, treatment of cardiomyocytes with TNF alpha caused a concentration-dependent increase in cyclase responsiveness to either forskolin, guanosine 5'-O-(3-thiotriphosphate) or isoproterenol, even though beta-adrenoceptor density was decreased by TNF alpha. The increase in adenylyl cyclase activity induced by TNF alpha was completely suppressed when the cells were cocultured with noradrenaline, a condition leading to an additive increase in Gi alpha level. The data indicate that the cytokine TNF alpha can potently modulate G protein-mediated signal transduction in rat cardiac myocytes. Although TNF alpha, like noradrenaline, exposure of the cells increased the level of membrane Gi alpha proteins, it did not decrease but rather caused an increase in adenylyl cyclase responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Diphosphate Ribose↗
The oxime HGG-12 as a muscarinic acetylcholine receptor antagonist without intrinsic activity in cardiac membranes.
Direct interactions of the bispyridinium oxime HGG-12 with muscarinic acetylcholine receptors were investigated in porcine cardiac atrial membranes. Competition binding experiments using the radiolabeled muscarinic receptor antagonist (3H)QNB revealed specific binding of HGG-12 to muscarinic acetylcholine receptors of porcine atrial membranes with a dissociation constant of 3.8 x 10(-7) mol/l. Muscarinic acetylcholine receptor-stimulated binding of the radiolabeled GTP analog (35S)GTP[S] to guanine nucleotide binding proteins (G-proteins) was used to study antagonistic and possible agonistic effects of HGG-12 at muscarinic acetylcholine receptors. HGG-12 completely inhibited carbachol- and oxotremorine-stimulated (35S)GTP[S] binding to pertussis toxin sensitive and insensitive G-proteins in a competitive manner. Inhibition constants (K1) of HGG-12 for blockade of carbachol- and oxotremorine-stimulated GTP[S]-binding (9.7 x 10(-7) mol/l and 1.7 x 10(-6) mol/l, respectively) were higher by about a factor of 100 than those of the muscarinic acetylcholine receptor antagonist atropine. In the absence of muscarinic acetylcholine receptor agonists. HGG-12 by itself had no stimulatory effect on (35S)GTP[S] binding in porcine atrial membranes. The results of this study show that the oxime HGG-12 is a competitive antagonist without intrinsic activity at porcine atrial muscarinic acetylcholine receptors. The stimulatory action of HGG-12 on muscarinic acetylcholine receptors which has been described by several authors is, therefore, suggested to be due to partial inhibition of acetylcholinesterase by the oxime rather than to direct agonism at muscarinic acetylcholine receptors.
Animals↗