[Life-threatening metabolic acidosis after ingestion of fire extinguisher powder]. / Lebensbedrohliche Acidose nach Ingestion von ABC-Löschpulver.

We present the case of a 31-year old male with ingestion of fire extinguisher powder in an attempted suicide. After consulting several poison information centres, the intoxication was initially classified as harmless; nevertheless, the patient was admitted to our intensive care unit for cardiopulmonary monitoring. Subsequently, due to the ingestion of ammonium sulphate and ammonium dihydrogen phosphate containing powder the patient developed severe metabolic acidosis with distinct electrolyte imbalance that required temporary haemodialysis.

[Anesthesia in children and adolescents with congenital heart defects]. / Anästhesie bei Kindern und Jugendlichen nach angeborenen Herzfehlern.

The incidence of congenital heart defects (CHD) has remained constant over many years; however, due to improved therapeutic options an increasing number of children and adolescents even with complex heart defects now reach adulthood. The increasing prevalence of adults with persisting or surgically corrected CHD as well as age-dependent non-cardiac comorbidities will increase the need for medical and non-cardiac surgical treatment in this population. Although elective medical care for these patients should be reserved for highly specialized centers, emergency treatment might become necessary in a non-specialized hospital setting as well. Due to the variety and complexity of CHD it is difficult to provide standardized guidelines for the anesthetic management. The treatment of patients with complex CHD requires a profound understanding of the underlying CHD and the current state of the hemodynamics by the anesthesiologist. Furthermore, typical comorbidities, such as chronic heart failure, altered coagulation and arrhythmia also have to be taken into account to ensure successful perioperative treatment. Especially in patients with shunt lesions or passive pulmonary blood flow the anesthetic management often substantially affects the hemodynamics and may be the starting point of severe decompensation. Awareness of anesthesia-induced changes of pulmonary and/or systemic vascular resistance as well as of preload alterations are the basis for successful anesthetic management. Finally, a multidisciplinary approach including cardiologists and radiologists in the planning is absolutely essential to achieve an optimal postoperative result for the patient.

[Rare complication after endoscopic discectomy]. / Seltene Komplikation der endoskopischen Nukleotomie.

Surgical treatment of the lumbar spine is a standard procedure in orthopedic and neurosurgery. After endoscopic discectomy an otherwise healthy patient developed massive dyspnea in combination with severe abdominal pain. Sonography revealed a large volume of free fluid in the abdominal cavity which proved to be surgical irrigation solution after computed tomography (CT) guided puncture. After insertion of a drainage channel fluid could be removed and the patient was transferred to a peripheral ward after a 24 h monitoring period. This review reports on the complications and anesthetic characteristics of percutaneous spinal interventions and presents differential diagnoses of postoperative dyspnea.

Pre-conditioning with synthetic CpG-oligonucleotides attenuates myocardial ischemia/reperfusion injury via IL-10 up-regulation.

The aim of the study was to investigate whether pre-conditioning with CpG-oligodeoxynucleotides (CpG-ODN) may change cardiac ischemia/reperfusion (I/R)-dependent inflammation and modulates infarct size and cardiac performance. WT and TLR9-deficient mice were pre-treated with 1668-, 1612- and H154-thioate or D-Gal as control. Priming with 1668-thioate significantly induced inflammatory mediators in the serum and a concomitant increase of immune cells in the blood and spleen of WT mice. Furthermore, it induced myocardial pattern recognition receptors and pro-inflammatory cytokines peaking 2 h after priming and a continuous increase of IL-10. 16 h after pre-conditioning, myocardial ischemia was induced for 1 h. Infarct size determined after 24 h of I/R was reduced by 75 % due to pre-conditioning with 1668-thioate but not in the other groups. During reperfusion, cytokine expression in 1668-thioate primed mice increased further with IL-10 exceeding the other mediators by far. These changes were observed neither in animals pre-treated with 1612- or H154-thioate nor in TLR9-deficient mice. The 1668-thioate-dependent increase of IL-10 was further supported by results of a micro-array analysis 3 h after begin of reperfusion. Block of IL-10 signaling increased I/R size and prevented influence of priming. In the group pre-treated with 1668-thioate, cardiac function was preserved 24 h, 14 days and 28 days after I/R, whereas animals without pre-conditioning exhibited impaired heart function 24 h and 14 days after I/R. The excessive 1668-thioate-dependent IL-10 up-regulation during pre-conditioning and after I/R seems to be the key factor for reducing infarct size and improving cardiac function. This is in agreement with the finding that IL-10 block prevents cardioprotection by pre-conditioning.

In vivo TLR9 inhibition attenuates CpG-induced myocardial dysfunction.

The involvement of toll-like receptor 9 (TLR9), a receptor for bacterial DNA, in septic cardiac depression has not been clarified in vivo. Thus, the aim of the study was to test possible TLR9 inhibitors (H154-thioate, IRS954-thioate, and chloroquine) for their ability to protect the cardiovascular system in a murine model of CpG oligodeoxynucleotide- (ODN-) dependent systemic inflammation. Sepsis was induced by i.p. application of the TLR9 agonist 1668-thioate in C57BL/6 wild type (WT) and TLR9-deficient (TLR9-D) mice. Thirty minutes after stimulation TLR9 antagonists were applied i.v. Survival was monitored up to 18 h after stimulation. Cardiac mRNA expression of inflammatory mediators was analyzed 2 h and 6 h after stimulation with 1668-thioate and hemodynamic parameters were monitored at the later time point. Stimulation with 1668-thioate induced a severe sepsis-like state with significant drop of body temperature and significantly increased mortality in WT animals. Additionally, there was a time-dependent increase of inflammatory mediators in the heart accompanied by development of septic heart failure. These effects were not observed in TLR9-D mice. Inhibition of TLR9 by the suppressive ODN H154-thioate significantly ameliorated cardiac inflammation, preserved cardiac function, and improved survival. This suppressive ODN was the most efficient inhibitor of the tested substances.

[Cardiopulmonary bypass in cardiac surgery]. / Kardiopulmonaler bypass in der herzchirurgie.

Cardiopulmonary bypass (CPB) is a standard procedure in cardiac surgery; however, apart from its therapeutic options a CPB might also initiate systemic and organ-specific complications, such as heart failure, renal and pulmonary dysfunction, impaired coagulation as well as neurological and cognitive dysfunction. The immunological response to the extracorporeal circulation generates systemic inflammation which often meets the definition of systemic inflammatory response syndrome (SIRS). The main inducers of SIRS are contact of blood with the artificial surfaces of the CPB, mechanical stress which affects the blood components and the extensive surgical trauma. Hence, a number of technical and surgical developments aim at reduction of the inflammatory response caused by the CPB. By reason of surgical demands, the majority of cardiothoracic procedures still depend on the use of CPB; however, there is an on-going development of new techniques trying to reduce the surgical trauma and the negative consequences of CPB. Here, minimized systems with biocompatible surfaces have been shown to be effective in attenuating the inflammatory response to CPB. Alternative procedures such as off-pump surgery may help to avoid CPB-associated complications but due to specific limitations will not replace conventional bypass surgery.

[Traumatic tricuspid valve insufficiency with right-to-left shunt: bridging using extracorporeal venovenous membrane oxygenation]. / Traumatische Trikuspidalklappeninsuffizienz mit Rechts-links-Shunt: "Bridging" mithilfe der extrakorporalen venovenösen Membranoxygenierung.

The case of a young male motor vehicle driver is reported who suffered multiple trauma in a car accident with pulmonary and cardiac contusions. In the course of severe pneumonia and traumatic tricuspid valve insufficiency a right-to-left shunt with refractory hypoxemia developed across a pre-existing atrial septal defect (ASD). The patient could be successfully treated by the combination of extracorporeal membrane oxygenation for bridging, interventional ASD occlusion and in the long-term by operative reconstruction of the tricuspid valve.

[Student evaluation of anesthesiological teaching: steering instrument of a continuous improvement process]. / Studentische Evaluation der anästhesiologischen Lehre : Steuerinstrument eines kontinuierlichen Verbesserungsprozesses.

BACKGROUND: The amendment to the higher education act ("Hochschulrahmengesetz") of 1998 postulates an evaluation of teaching for quality assurance. Hence, in the winter semester of 2004 the University Medical Center of Bonn introduced a semester questionnaire for students to evaluate the quality of teaching (EVALON). This evaluation is designed to be an objective benchmarking tool which is used for the distribution of university funds. It is also a steering instrument for direct improvement of teaching in clinical subjects. The aim of this study was to investigate, whether EVALON improved the quality of teaching between 2006 and 2010 and whether the department of anesthesiology improved its ranking in comparison with the other participating institutes. MATERIALS AND METHODS: Data from the EVALON questionnaire from the years 2006-2010 were analyzed for improvements in the quality of teaching in anesthesiology. This study focused on three essential contents of the EVALON questionnaire (structural content and organizational procedure of lectures and seminars, course presentation), which were used for the generation of a ranking list of all participating medical institutes and departments. On the basis of these results, 12.5% of the funding was assigned for educational purposes. RESULTS: There was an average return rate of the questionnaires of 74.5%. A significant increase in the overall assessment score of 43.4% could be observed from 5.3 in the summer semester of 2006 to 7.6 in the winter semester of 2009/10. The evaluation score for the department of anesthesiology concerning structural content of seminars and lectures increased by 79% from 4.8 in 2006 to 8.6 in 2010. The quality of organizational procedure was evaluated with a score of 4.9 in 2006 and improved by 74% to 8.5 in 2010. The course presentation skills of the teachers as evaluated by EVALON improved by 61% from a score of 5.2 in 2006 to 8.4 in 2010. In comparison with all other participating medical institutes the department of anesthesiology improved its ranking from position 36 in the winter semester 2006 to position 2 in the summer semester 2010. CONCLUSIONS: The reorganization of teaching anesthesiology, directly controlled by the results of EVALON improved the ranking of the department of anesthesiology. There was also a concomitant increase of the performance-oriented allocation of funds assigned to the department of anesthesiology based on the EVALON results.

Systemically administered ligands of Toll-like receptor 2, -4, and -9 induce distinct inflammatory responses in the murine lung.

OBJECTIVE: To determine whether systemically administered TLR ligands differentially modulate pulmonary inflammation. METHODS: Equipotent doses of LPS (20 mg/kg), CpG-ODN (1668-thioat 1 nmol/g), or LTA (15 mg/kg) were determined via TNF activity assay. C57BL/6 mice were challenged intraperitoneally. Pulmonary NFκB activation (2 h) and gene expression/activity of key inflammatory mediators (4 h) were monitored. RESULTS: All TLR ligands induced NFκB. LPS increased the expression of TLR2, 6, and the cytokines IL-1αß, TNF-α, IL-6, and IL-12p35/p40, CpG-ODN raised TLR6, TNF-α, and IL12p40. LTA had no effect. Additionally, LPS increased the chemokines MIP-1α/ß, MIP-2, TCA-3, eotaxin, and IP-10, while CpG-ODN and LTA did not. Myeloperoxidase activity was highest after LPS stimulation. MMP1, 3, 8, and 9 were upregulated by LPS, MMP2, 8 by CpG-ODN and MMP2 and 9 by LTA. TIMPs were induced only by LPS. MMP-2/-9 induction correlated with their zymographic activities. CONCLUSION: Pulmonary susceptibility to systemic inflammation was highest after LPS, intermediate after CpG-ODN, and lowest after LTA challenge.

Cytokines as emerging targets in the treatment of heart failure.

Recent studies have identified the importance of biologically active molecules such as neurohormones in disease progression in heart failure. More recently it has become apparent that in addition to neurohormones another portfolio of biologically active molecules termed cytokines are also expressed in the setting of heart failure. This article reviews recent clinical and experimental material which suggest that the cytokines such as tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6) may represent another class of biologically active molecules that are responsible for the development and progression of heart failure. In addition, we also review the early results from clinical trials that have utilized various targeted anti-cytokine strategies in patients with heart failure.

Role of Toll-like receptor 4 for the pathogenesis of acute lung injury in Gram-negative sepsis.

BACKGROUND AND OBJECTIVE: Proinflammatory cytokines as well as nitric oxide (NO) play a major role in mediating the response to lipopolysaccharide (LPS). The present study tested the hypothesis that LPS induces proinflammatory cytokines in the lung via the Toll-like receptor 4 (TLR4)/CD14 signalling cascade. METHODS: Control mice and TLR4-deficient (TLR4-D) mice were used to test TLR4-mediated effects of LPS. Both strains received either Escherichia coli LPS (20 mg kg-1 intraperitoneal) or saline and their lungs were collected at different time points. Pulmonary nuclear factor kappaB (NFkappaB) activation was investigated with electromobility shift assay. mRNA expression of inflammatory mediators and their corresponding receptors were detected with Ribonuclease Protection Assay. Protein expression was detected by ELISA and western blotting. Inducible NO synthase (iNOS) expression was monitored by RT-PCR and iNOS activity by conversion of l-arginine to citrulline. Immune cells were sampled by bronchoalveolar lavage (BAL) and classified. RESULTS: LPS application induced CD14-, but not TLR4 protein expression in control mice. Activation of pulmonary NFkappaB was observed within 60 min in control, but not in TLR4-D mice. Six hours of LPS administration induced a significant increase in pulmonary tumour necrosis factor alpha-, interleukin-1beta- and interleukin-6 mRNA and protein expression in control mice compared to TLR4-D mice. Furthermore, LPS induced a significantly higher increase of the iNOS expression and catalytic activity in control mice than in TLR4-D mice. BAL revealed an increase in total cell count in all LPS treated mice. CONCLUSION: Our findings suggest that TLR4 plays a key role for regulating the expression of relevant cytokines within the lung during endotoxic shock.

Myocardial cytokine gene expression is higher in aortic stenosis than in idiopathic dilated cardiomyopathy.

OBJECTIVE: To investigate cytokine gene expression in patients with aortic valve stenosis (AS) and with idiopathic dilated cardiomyopathy (DCM), and to correlate wall stress with myocardial proinflammatory cytokine gene expression. METHODS: Human left ventricular (LV) myocardial biopsies were obtained for subsequent reverse transcription polymerase chain reaction of tumour necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and IL-6 mRNA. The study population consisted of 24 patients with AS and 10 patients with idiopathic DCM. RESULTS: Patients with AS had a larger ejection fraction (56 (5) v 37 (4)%, p < 0.01), smaller LV end diastolic volumes (146 (11) v 267 (21) ml, p < 0.01), and lower end systolic wall stress (44 (7) v 112 (11) kdyn/cm2, p < 0.001). Upregulation of TNFalpha, IL-1beta, and IL-6 gene expression was detected in both groups. However, TNFalpha gene expression was significantly higher in AS than in DCM (p = 0.009). No correlation was found between haemodynamic parameters and TNFalpha gene expression. In patients with AS there was a strong inverse relation between circulating TNFalpha and TNFalpha gene expression (r = -0.685, p = 0.014), between circulating TNFalpha and IL-1beta gene expression (r = -0.664, p = 0.018), and between soluble TNF receptor 2 and TNFalpha gene expression (r = -0.685, p = 0.020). Myocardial gene expression of TNFalpha was significantly higher in patients with well compensated AS than in patients with decompensated AS (p = 0.017). Similarly, patients with decompensated DCM were characterised by significantly lower TNFalpha gene expression than were patients with well compensated DCM (p = 0.011). CONCLUSION: TNFalpha gene expression is significantly higher in patients with pressure overload than in normal hearts, in patients with idiopathic DCM, and in patients with compensated versus decompensated heart failure. Secondly, in patients with AS proinflammatory cytokine gene expression did not affect systolic performance. The higher TNFalpha gene expression in patients with compensated heart failure suggests that cytokine gene expression has an adaptive role in the early phase of LV remodelling.

[Cytokines and heart failure]. / Die Bedeutung von Zytokinen bei der Entstehung einer Herzinsuffizienz.

Chronic heart failure is a major cause for mortality and morbidity in western civilizations. Previous hypothesises regarding the pathogenesis of chronic heart failure did not sufficiently explain the aetiology and the progression of the disease. However, it has been shown that a group of peptides called cytokines are expressed during chronic heart failure and that cytokines might play an important role for the pathogenesis. The expression of cytokines can be modulated from specific ACE-inhibitors as well as from different beta-blockers and angiotensin type 1 antagonists. Numerous investigations have shown that cytokines depress left ventricular function and can be responsible for different characteristics of chronic heart failure. The present article resumes experimental and clinical investigations and recent pharmacologic attempts for the treatment of chronic heart failure. The previous results demonstrate the importance to further investigate anti-inflammatory approaches to treat chronic heart failure.

Group B Streptococcus induces TNF-alpha gene expression and activation of the transcription factors NF-kappa B and activator protein-1 in human cord blood monocytes.

It has been postulated that production of TNF-alpha is central to the pathogenesis of septic shock induced by group B Streptococcus (GBS). In vitro studies using human cord blood monocytes have demonstrated that GBS induces TNF-alpha secretion, but little is known about the intracellular signaling pathways of TNF-alpha induction. In this report we show that heat-killed serotype III GBS induces host cell signal transduction pathways that lead to activation of the transcription factors NF-kappaB and AP-1. Using adenoviral transfer of IkappaBalpha (IkappaBalpha overexpression), the production of TNF-alpha induced by whole GBS was inhibited by only 20%. We also show that the p38 mitogen-activated protein kinase (MAPK) pathway is involved in GBS-induced TNF-alpha secretion, because TNF-alpha protein and mRNA levels in the presence of a specific inhibitor of p38 MAPK, SB 202190, were dramatically diminished. EMSAs showed that SB 202190 inhibited GBS-induced AP-1 activation, but had no effect on NF-kappaB-DNA binding activity. These results indicate that both NF-kappaB and AP-1 (via p38 MAPK) are involved in the regulation of TNF-alpha production in GBS-stimulated neonatal monocytes. Therefore, disrupting the signal transduction pathways induced by GBS has the potential to attenuate the production of immune response mediators, thereby halting or possibly reversing the course of this potentially fatal disease.

In vivo expression of proinflammatory mediators in the adult heart after endotoxin administration: the role of toll-like receptor-4.

Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and nitric oxide (NO) may play a role in lipopolysaccharide (LPS)-induced cardiac depression. Toll-like receptor-4 (TLR-4) mediates the cytokine response to LPS in immune cells. TLR-4 also is expressed in human and murine myocardial tissue. Therefore, the hypothesis that LPS induces proinflammatory cytokines in the heart via TLR-4 was tested. C3H/HeJ (TLR-4 deficient) and C3HeB/FeJ mice were studied. LPS induced a robust increase in myocardial TNF-alpha and IL-1beta mRNA in C3HeB/FeJ mice. The response in C3H/HeJ mice was blunted and delayed. Myocardial TNF-alpha and IL-1beta protein levels were higher in C3HeB/FeJ mice, as were inducible NO synthase protein and NO production. Activation of myocardial NF-kappaB was observed within 30 min in C3HeB/FeJ mice but not in C3H/HeJ mice. These findings suggest that myocardial TLR-4 is involved in signaling cytokine production within the heart during endotoxic shock.

[Implantable cardioverter/defibrillator: long-term stability of the defibrillation threshold with a unipolar electrode configuration (active-can")]. / Implantierbarer Kardioverter-/Defibrillator: Langzeitstabilität der Defibrillationsschwelle mit einer unipolaren Elektrodenkonfiguration ("Active-Can").

The majority of cardioverter/defibrillator (ICD) implantations are currently performed with a non-thoracotomy approach. From November 1993 to January 1995, 46 patients underwent implantation of a PCD 7219C with an "active-can" lead configuration at our institution. While the chronic stability of the defibrillation threshold (DFT) for an epicardial lead system is well established, the results are still inconsistent for non-thoracotomy lead systems. Accordingly, the aim of the present study was to compare the acute and chronic defibrillation thresholds of the ICDs implanted with an "active-can" lead system in order to assess the chronic stability of these systems. The defibrillation energy requirements were measured at implant, prior to hospital discharge, three, six and twelve months after implantation of the defibrillator. The patient group consisted of 8 females and 38 males with a mean age of 57.2 years. The mean left ventricular ejection fraction was 43.8%. The most frequent underlying heart disease was coronary artery disease in 31 of 46 patients. Eight patients had idiopathic dilated cardiomyopathy. In 39 of 46 patients, the defibrillation threshold could be successfully determined at all 4 time points after implantation. The mean defibrillation energy requirement at the time of implantation was 9.2 +/- 5.9 Joules (J). The subsequent mean energy requirements were 7.6 +/- 4.8 J at pre-hospital discharge, 8.6 +/- 5.7 J at the 3 month, 8.1 +/- 6.0 J at the 6 month and 8.6 +/- 5.8 J at the 12 month follow-up visits. The mean defibrillation threshold was lowest at the time of prehospital discharge, significantly lower than at the time of initial implantation (p = 0.021). However, at all later time points up to one year, there was no significant difference in the DFT as compared with the time of initial implantation. Comparing the DFT at the time of implantation and the DFT at all other time points, there were no significant differences (9.23 vs. 8.56 J, p = 0.291). Although there was an initial decrease in the DFT at seven to ten days, the long-term stability of the DFT up to one year remained stable in the devices with the "active-can" lead system.

Gender differences in the expression of heat shock proteins: the effect of estrogen.

The heat shock proteins (HSPs) are an important family of endogenous, protective proteins that are found in all tissues. In the heart, HSP72, the inducible form of HSP70, has been the most intensely studied. It is well established that HSP72 is induced with ischemia and is cardioprotective. Overexpression of other HSPs also is protective against cardiac injury. Recently, we observed that 17beta-estradiol increases levels of HSPs in male rat cardiac myocytes. We hypothesized that there were gender differences in HSP72 expression in the heart secondary to estrogen. To test this hypothesis, we examined cardiac levels of HSP72 by ELISA in male and female Sprague-Dawley rats. In addition, three other HSPs were assessed by Western blot (HSP27, HSP60, and HSP90). To determine whether estrogen status affected HSP72 expression in other muscles or tissues, two other muscle tissues, slow twitch muscle (soleus muscle) and fast twitch muscle (gastrocnemius muscle), were studied as well as two other organs, the kidney and liver. Because HSP72 is cardioprotective, and females are known to have less cardiovascular disease premenopause, the effects of ovariectomy were examined. We report that female Sprague-Dawley rat hearts have twice as much HSP72 as male hearts. Ovariectomy reduced the level of HSP72 in female hearts, and this could be prevented by estrogen replacement therapy. These data show that the expression of cardiac HSP72 is greater in female rats than in male rats, due to upregulation by estrogen.

Brief murine myocardial I/R induces chemokines in a TNF-alpha-independent manner: role of oxygen radicals.

Early chemokine induction in the area at risk of an ischemic-reperfused (I/R) myocardium is first seen in the venular endothelium. Reperfusion is associated with several induction mechanisms including increased extracellular tumor necrosis factor (TNF)-alpha, reactive oxygen intermediate (ROI) species formation, and adhesion of leukocytes to the venular endothelium. To test the hypothesis that chemokine induction in cardiac venules can occur by ROIs in a TNF-alpha-independent manner, and in the absence of leukocyte accumulation, we utilized wild-type (WT) and TNF-alpha double-receptor knockout mice (DKO) in a closed-chest mouse model of myocardial ischemia (15 min) and reperfusion (3 h), in which there is no infarction. We demonstrate that a single brief period of I/R induces significant upregulation of the chemokines macrophage inflammatory protein (MIP) -1 alpha, -1 beta, and -2 at both the mRNA and protein levels. This induction was independent of TNF-alpha, whereas levels of these chemokines were increased in both WT and DKO mice. Chemokine induction was seen predominantly in the endothelium of small veins and was accompanied by nuclear translocation of nuclear factor-kappa B and c-Jun (AP-1) in venular endothelium. Intravenous infusion of the oxygen radical scavenger N-2-mercaptopropionyl glycine (MPG) initiated 15 min before ischemia and maintained throughout reperfusion obviated chemokine induction, but MPG administration after reperfusion had begun had no effect. The results suggest that ROI generation in the reperfused myocardium rapidly induces C-C and C-X-C chemokines in the venular endothelium in the absence of infarction or irreversible cellular injury.