[Management and Outcome of Surgery in Patients with Severe Pulmonary Hypertension--A Single-Center Experience]. / Management und postoperatives Überleben bei chirurgischen Eingriffen an Patienten mit schwerer pulmonaler Hypertonie--etrospektive Analyse eines Zentrums.

BACKGROUND: Patients with pulmonary hypertension (PH) are at high risk when undergoing surgery. Up to one-third of patients suffer complications; recent studies report a mortality rate of 1 to 7%. Frequent events are deterioration of right heart function and infectious or bleeding complications. METHODS: Data of patients (age ≥ 18) with precapillary PH who need to undergo elective surgery between January 2006 and March 2015 were included in this retrospective analysis. All patients who were planned for surgery underwent the same procedure. First, patients were evaluated in the PH center. Thereafter, PH-relevant data were discussed with the surgeon/anesthesiologist team for risk-adapted planning of anesthesia and intervention. The present analysis comprises patient characteristics and information about surgery and post-interventional course. RESULTS: This study analyzes 31 surgical procedures carried out in PH patients (male: n = 8; PH-group I: n = 23, group III: n = 3, group IV: n = 5, mean age: 59.5 ± 15.3 years). Patients were characterized by compromised hemodynamics and exercise capacity: pulmonary vascular resistance: 805.4 ± 328.5 dyn*s*cm(-5), mean pulmonary arterial pressure: 46.3 ± 9.3 mmHg, 6-minute walking distance: 350.3 ± 123.3 m.The majority of interventions were performed under general anesthesia (n = 24). In 25 cases, the intraoperative monitoring was complemented with right heart catheterization.Eight interventions were associated with complications, three of which were serious. One patient died postoperatively owing to sepsis and right heart failure. CONCLUSION: A careful and structured planning of surgical interventions in patients with PH and the choice of surgical procedure and anesthesia adapted to the conditions of PH might help avoid complications. Further multicentric studies are needed.

Intraoperative sRAGE kinetics. A new age-related outcome predictor of cardiac surgery.

BACKGROUND: Glycated proteins (advanced glycation endproducts, AGE) in tissue are associated with degenerative diseases. This study evaluated the role of sRAGE (soluble receptor for advanced glycation endproducts), a decoy receptor of AGEs in blood, for the outcome of patients after coronary artery bypass grafting (CABG). METHODS: A total of 90 patients undergoing CABG were analysed in two centres. Perioperative blood samples were collected before surgery up to 1 week postoperatively. sRAGE was measured by ELISA. Patients were subdivided regarding age (< 64 versus > 70 years, 14 % versus 35 % female), euroSCORE (< 3 versus > 4, 14 % versus 29 % female) and sRAGE changes between sternotomy and end of the operation (< 30 % versus > 45 %, 33 % versus 33 % female) and subsequently analysed with respect of postoperative outcome parameters. RESULTS: Preoperative sRAGE values did not correlate with the outcome of the patients. sRAGE levels increase within 10 min from 1,539 ± 96 to 5,311 ± 187 pg/ml after sternotomy, then returning to baseline levels within 2 days after surgery. Comparing the analysed possible risk factors age, euroSCORE and sRAGE changes, no difference was observed regarding 30-day mortality. Age and the euroSCORE are superior with respect of tachyarrythmia, whereas sRAGE kinetics seems to be superior with respect of prolonged postoperative respiration time/stay in the intensive care unit or catecholamine support. CONCLUSION: A prolonged, increased intraoperative sRAGE level is a new outcome predictor for patients undergoing CABG surgery, mutually complementary to the euroSCORE.

Glutamine and alanine-induced differential expression of intracellular IL-6, IL-8, and TNF-α in LPS-stimulated monocytes in human whole-blood.

To investigate the effects of the commonly-used immunomodulators l-glutamine, l-alanine, and the combination of both l-alanyl-l-glutamine (Dipeptamin(®)) on intracellular expression of IL-6, IL-8, and TNF-α during endotoxemia, lipopolysaccharide (LPS)-stimulated human monocytes in a whole blood system were investigated by flow cytometry. Whole blood of twenty-seven healthy volunteers was stimulated with LPS and incubated with three different amino acid solutions (1. l-glutamine, 2. l-alanine, 3. l-alanyl-l-glutamine, each concentration 2 mM, 5 mM, incubation time 3 h). CD14(+) monocytes were phenotyped in whole-blood and intracellular expression of cytokines was assessed by flow cytometry. Our investigations showed for the first time in whole blood probes, imitating best physiologically present cellular interactions, that l-glutamine caused a dose-independent inhibitory effect on IL-6 and TNF-α production in human monocytes stimulated with LPS. However, l-alanine had contrary effects on IL-6 expression, significantly upregulating expression of IL-6 in LPS-treated monocytes. The impact of l-alanine on the expression of TNF-α was comparable with glutamine. Neither amino acid was able to affect IL-8 production in LPS-stimulated monocytes. The combination of both did not influence significantly IL-6 and IL-8 expression in monocytes during endotoxemia, however strongly reduced TNF-α production. For the regulation of TNF-α, l-glutamine, l-alanine and the combination of both show a congruent and exponentiated downregulating effect during endotoxemia, for the modulation of IL-6, l-glutamine and l-alanine featured opposite regulation leading to a canceling impact of each other when recombining both amino acids.

[Pulmonary hypertension due to chronic lung disease. Recommendations of the Cologne Consensus Conference 2010]. / Pulmonale Hypertonie bei chronischen Lungenerkrankungen. Empfehlungen der Kölner Konsensus-Konferenz 2010.

The 2009 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) in chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians feel sometimes inclined to treat other form of pulmonary hypertension which may affect quality of life and survival of these patients in a similar manner. In June 2010, a group of German experts met in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. The conference was sponsored by the German Society of Cardiology, the German Society of Respiratory Medicine and the German Society of Pediatric Cardiology. One of the working groups was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The recommendations of this working group are summarized in the present paper.

[Perioperative infusion therapy in children].

A volume replacement therapy compensates a reduced intravascular volume to stabilize and maintain hemodynamics and vital signs. For this therapy, a physiologically-based solution comprising both, osmotic and colloid osmotic components, should be administered. The basic requirement for a sufficient fluid replacement and volume resuscitation therapy in children are the profound and special knowledge of the physiological and pathophysiological interactions in water balance and electrolyte metabolism in childhood, the pharmacology of the applied solutions and the adequate monitoring of this fluid and volume replacement therapy. Wrong dosages and side effects are reasons for a negative postoperative outcome in children.

[Training of anesthesiologists in Germany].

A structured and well-organized postgraduate professional education in medical doctors is an important and necessary component in health care these days. It is the foundation for a high quality and safety of physicians' daily work. The article describes the anesthesiological educational program, which is required to finish anesthesia residency in Germany successfully.

[Postoperative therapy for pain in children].

Treatment of acute pain is one of the most important tasks of perioperative pediatric anesthesia. Pain-relieving drugs are usually administered on the basis of the concept of balanced analgesia, which involves a combination of analgesics with either synergic or additive effects. The concept of balanced analgesia is successful under many circumstances, but continuous efforts are needed to improve management in dificult cases. The key problem is to decide if a child has pain. Establishing a high standard at an institution requires a regular evaluation and documentation of pain scores. Non-opioid analgesics are frequently administered just in the induction of anesthesia due to their long-term effects, and then combined with opioids or regional anesthetic techniques. The present review focuses on non-opioid analgesics that can be intravenously injected for the perioperative treatment of acute pain.

[Sepsis and multiple organ dysfunctions--pathophysiology and the topical concepts of treatment].

Severe sepsis with multiple organ dysfunctions is still the leading cause of death in non-cardiac intensive care units (ICU). The incidence is expected to rise in the future due to the growing number of older and immunocompromized patients, the use of invasive procedures, and an increase in the percentage of aggressive or resistant microorganisms. Despite the enormous investment in critical care resources, severe sepsis mortality remains to be high and ranges from 28 to 50%. Based on the disappointing experiences with anti-inflammatory strategies, the authors now realize that sepsis is more than just an inflammation. By taking into account pathophysiological changes, the new therapeutic concepts combine successful modulation with an improvement of the ICU management of multiple organ dysfunctions. This review discusses the actual sepsis intensive care concepts that may be useful in reducing unacceptable high mortality rates in patients with severe sepsis.

A sirs-based automated alarm system for the diagnosis of sepsis after burn injury.

The present study examined the effectiveness of an automated systemic inflammatory response syndrome (SIRS)-based alarm system for the early detection of sepsis in adult burn patients. In addition, the relevance of the sepsis criteria from the American Burn Association (ABA) and the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) for this patient group was determined. In this prospective observational study, we included 41 consecutive patients who were admitted to our burn ICU within a one-year period. SIRS alarms were calculated for these patients according to predefined criteria using the PREDEC ALARM automated alarm system and alarms generated according to ABA criteria and daily Sequential Organ Failure Assessment (SOFA) results. The alarms were not visible to the treating doctors and nurses. The alarms identified were related to episodes of sepsis with positive blood cultures. Twenty-one sepsis events were recorded in 41 patients. The receiver operating characteristic (ROC) curve revealed an area under the curve (AUC) of 0.72 for alarms using 2 SIRS criteria, 0.77 for 3 SIRS criteria, and 0.61 for 4 SIRS criteria. AUC values of 0.53 and 0.59 were calculated for the ABA criteria and Sepsis-3 definition, respectively. An alarm system using 3 SIRS criteria proved to be suitable for the early detection of sepsis in burn patients. The frequent number of false alarms requires further refinement of the alarm system. Based on the results of our study, the ABA criteria and the Sepsis-3 definition provide no advantages over the SIRS criteria in the early diagnosis of sepsis after burn injury.

Cette étude évalue l'efficacité d'un système automatique fondé sur les paramètres de SIRS pour la détection précoce du sepsis chez des adultes brûlés. En outre, il étudie la pertinence des critères d'infection de l'ABA et des critères de sepsis selon la conférence Sepsis- 3 chez ces patients. Nous avons inclus 41 patients consécutifs, admis dans notre USI pour brûlés, dans cette étude observationnelle rospective. Les alarmes du système automatique PREDEC ALARM ont été calibrées selon les critères de l'ABA et le score SOFA et comparés aux 21 épisodes septiques à hémocultures positives. Elles étaient cachées aux médecins et infirmières. Les aires sous courbes ROC étaient de 0,72 pour les alarmes basées sur 2 critères de SIRS ; 0,77 pour 3 critères et 0,61 pour 4 critères. Elles étaient de 0,53 pour les critères ABA et 0,59 pour les critères Sepsis-3. Une alarme basée sur 3 critères de SIRS semble donc être utilisable pour détecter précocement un sepsis chez les brûlés, mais le nombre élevé de faux positif nécessite un affinement du système. Les critères ABA et Sepsis-3 ne semblent pas plus efficaces dans ce but.

[Preoperative hypervolemic hemodilution with 6% hydroxyethyl starch 130/0,4 (HES 130/ 0.4) solution as a way of reducing needs for donor blood transfusion].

UNLABELLED: The efficacy of hypervolemic hemodilution (HHD) in reducing the rate of donor blood transfusion is controversely discussed. The present prospective, randomized, clinical study analyzes the impact of HHD with 6% hydroxyethyl starch (HES) 130/0.4 solution on the rate transfusion, laboratory parameters, and the incidence of complications as compared with those in the control group receiving no preoperative HHD. MATERIAL AND METHODS: 80 patients who had undergone total prostatectomy or cystectomy were randomized into 2 groups. Before anesthesia, the HHD group (n=40) received 15 ml/kg of 6% HES 130/0.4 solution. In the HHD and control (n=40) groups, 6% HES 130/0.4 was intraintraoperatively infused in its maximum dose of 33 ml/kg according to the patients' needs. Indicationsf or blood transfusion trigger were Hb <5 g/dl or packed cell volume < 0.24. Laboratory parameters (Hb, PCV, platelets, prothrombin index, prothrombin time, thrombin time, fibrinogen, antithrombin III were measured before surgery, after HHD and 2, 24, and 48 hours after surgery. The mean blood pressure (MBP), heart rate (HR), and central venous pressure (CVP) were determined before surgery, after HHD, and 2 hours postsurgery. Statistical measurements were made in all patients from the HHD and control groups, as well as in a subgroup, in which intraoperative blood loss was greater than 30% of the total blood volume (70 ml/kg body weight). RESULTS: Demographic data and surgical techniques were similar in both groups. After HHD, CVP rose significantly. The changes in MBP and HR were statistically insignificant. There were no complications after HHD. Of the 40 HHD-group patents, 5 needed donor blood transfusion while in the control group blood was transfused to 10 of the 40 patients in the control group. Comparing both groups showed a lower need for blood transfusion in the HHD-group patients than in the controls (10 versus 24 packed red cells). The postoperative Hb values showed no difference between both groups. CONCLUSIONS: Preoperative HHD in patients undergoing surgery with expected >30% blood loss leads to decreased needs for blood transfusion. The method is safe and easy-to-use.

[General and supportive therapy of pulmonary arterial hypertension]. / Allgemeine und supportive Therapie der pulmonal arteriellen Hypertonie: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted and supportive treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to general and supportive therapy of PAH. This article summarizes the results and recommendations of this working group.

[Decompensated right heart failure, intensive care and perioperative management in patients with pulmonary hypertension]. / Dekompensierte Rechtsherzinsuffizienz, Intensiv- und Perioperativ-Management bei Patienten mit pulmonaler Hypertonie: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the management of decompensated right heart failure, intensive care management and perioperative management in patients with pulmonary hypertension. This article summarizes the results and recommendations of the working group on decompensated right heart failure, intensive care and perioperative management in patients with pulmonary hypertension.

Multimodal evoked potential monitoring in asleep patients versus neurological evaluation in awake patients during carotid endarterectomy: a single-centre retrospective trial of 651 patients.

BACKGROUND: A controversy exists regarding which monitoring technique is superior in cases in which general anesthesia (GA) is necessary for carotid endarterectomy (CEA). Multimodal evoked potential (mEP) monitoring was investigated under GA during CEA and compared with a historical control group undergoing neurological evaluations awake under loco-regional anesthesia (LA). METHODS: We retrospectively studied 651 patients undergoing elective CEA. In groupHISTORY (N.=349; 1997-1999) LA was provided using superficial or deep/superficial cervical plexus blocks. In groupmEP, (N.=302; 2009-2013) GA was performed by administering remifentanil/propofol infusion. The multimodal EPs included the median-nerve-somatosensory and motor evoked potentials. The primary outcome was the rate of technical failure. The arterio-arterial shunt rate and immediate postoperative motor outcomes were also compared. RESULTS: GroupmEP showed a significantly lower rate of technical failure (OR 0.17; CI 0.03-0.6; P=0.002). Because the groups differed systematically, logistic regression analysis was used to compare shunt rates and motor outcomes. Since shunt rates were 8.3% (groupmEP) versus 8.2% (groupHISTORY), but logistic regression model showed significant differences (OR 3.77; CI 1.67-8.95; P=0.001) correct comparison was impossible. Immediate postoperative deficits were 4.3% (groupmEP) and 4.9% (groupHISTORY); logistic regression analysis: transient OR 0.77, CI 0.28 to 0.22, P=0.61 and permanent OR 0.37, CI 0.02-7.74, P=0.49. CONCLUSION: Monitoring mEPs was associated with less technical failure than awake evaluation and showed similar motor outcomes. Because the groups differed systematically, the interpretation of shunt rates was impossible. Monitoring mEP should be considered to detect intraoperative ischemia in cases in which patients undergo CEA under GA.

Transcranial motor evoked potentials during anesthesia with desflurane versus propofol--A prospective randomized trial.

OBJECTIVE: This study aimed to evaluate differences in transcranial electrical motor evoked potential (tcMEP) amplitudes between desflurane/remifentanil and propofol/remifentanil anesthesia treatment plans in patients without preexisting motor deficits (PMDs) undergoing carotid endarterectomy (CEA). METHODS: This prospective trial included 21 patients who were randomly assigned to an effect group (Group(DESFLURANE); n=14) or a control group (Group(STANDARD-PROPOFOL); n=7). tcMEP amplitudes were measured 35 min post-induction (T1) either with desflurane or propofol. Treatment was then changed to propofol in Group(DESFLURANE). After an additional 35 min, the tcMEP amplitudes were reevaluated (T2). Differences in amplitudes (DW) between T1 and T2 were calculated for each patient, and the means of these differences were compared between groups. RESULTS: tcMEPs were recorded in all 21 patients. At T1, the mean amplitude was 840.1 (SD 50.3) µV and 358.9 (SD 74) µV for Group(STANDARD-PROPOFOL) and Group(DESFLURANE), respectively. The absolute mean difference (T1-T2) between groups was -496.75 µV (p=0.0006). CONCLUSION: Desflurane reduces the tcMEP amplitude significantly more than propofol in patients without PMDs undergoing CEA. SIGNIFICANCE: TcMEPs were recorded in all patients regardless of the anesthesia regimen. In patients with initially small amplitudes, desflurane may limit tcMEP recording because it produces a remarkable amplitude reduction, even in patients without PMDs.

Perioperative microbiologic monitoring of tracheal aspirates as a predictor of pulmonary complications after cardiac operations.

The value of preoperative and early postoperative microbiologic testing of tracheal aspirates as a prognostic indicator of the development of pneumonia was evaluated in a prospective study of 213 cardiac surgical patients. Tracheal aspirates were obtained immediately after intubation and after the patient's arrival at the intensive care unit. Diagnosis of pneumonia was accepted if at least three of the following criteria were fulfilled: leukocytosis > 15,000 cells/mm3, body temperature >38.5 degrees C, positive results of auscultation, positive results of radiography (new infiltrates that seemed to be consistent with pneumonia), and increased core-reactive protein for more than 2 days after operation. Potentially pathogenic microorganisms were found in 54 (25.4%) of the preoperative tracheal aspirates and in 27 (12.7%) of the early postoperative tracheal aspirates. Positive microbiologic findings correlated with pneumonia in the postoperative course in 24.1% (p < 0.001) if the preoperative culture results were positive, in 48.2% (p < 0.001) if the postoperative culture results were positive, and in 44.0% (p < 0.001) if both were positive. The risk of pneumonia was increased in male patients (p < 0.05) and in patients with chronic obstructive pulmonary disease (p < 0.05). Demographic variables, smoking, acute pulmonary symptoms, temperature, leukocyte count at the day of the operation, and data on the operation and the extracorporeal circulation were not significantly related to pneumonia in the early postoperative course. The risk of development of postoperative pneumonia is significantly higher among patients with colonization of the lower respiratory tract. Positive culture results in routine microbiologic monitoring of tracheal aspirates are predictive of pulmonary complications after cardiac operations.

Tumor necrosis factor-alpha production in whole blood after cardiopulmonary bypass: downregulation caused by circulating cytokine-inhibitory activities.

OBJECTIVES: Cardiopulmonary bypass is associated with the release of proinflammatory cytokines (tumor necrosis factor alpha, interleukin 1beta, interleukin 6, and interleukin 8) and anti-inflammatory cytokines (interleukin 10 and transforming growth factor beta(1)). On the one hand this cytokine release is related to the postoperative systemic inflammatory response syndrome, and on the other hand it is related to deterioration of the immune system, for example in monocyte or polymorphonuclear neutrophil function, leading to an increased susceptibility to infections. To gain further insight into the alterations of immune cell reactivity and possible regulatory mechanisms, we studied lipopolysaccharide-induced tumor necrosis factor alpha synthesis in whole blood from cardiac surgical patients. METHODS: Fifteen patients undergoing elective heart surgery with cardiopulmonary bypass were included in the study. Ex vivo lipopolysaccharide-induced tumor necrosis factor alpha synthesis was measured in a whole blood assay before, during, and after bypass. Corresponding tumor necrosis factor alpha messenger RNA levels were determined by semiquantitative reverse transcriptase-polymerase chain reaction. In addition, the influence of patient serum on whole blood responsiveness and its relationship to anti-inflammatory cytokines were evaluated in vitro. RESULTS: Tumor necrosis factor alpha synthesis was significantly reduced after 30 minutes of cardiopulmonary bypass and showed the lowest values at the end of bypass (mean +/- SD 0.109 +/- 0.105 ng/10(6) white blood cells after 30 minutes of bypass and 0.050 +/- 0.065 ng/10(6) white blood cells at the end of bypass, vs 0.450 +/- 0.159 ng/10(6) white blood cells preoperatively, P <.001). As a further indication of reduced cytokine biosynthesis, diminished messenger RNA levels for tumor necrosis factor alpha were detected. Serum withdrawn from patients at the end of cardiopulmonary bypass reduced tumor necrosis factor alpha synthesis in heterologous blood from healthy volunteers highly significantly to 39.93% +/- 23.18% relative to control serum (P =.005) and preoperatively drawn serum (P =.024). This effect was dose dependent and was not specific for lipopolysaccharide-induced tumor necrosis factor alpha synthesis. Anesthesia and heparin administration did not influence tumor necrosis factor alpha production significantly. Ex vivo tumor necrosis factor alpha synthesis was negatively related to interleukin 10 serum levels, positively but weakly related to interleukin 4, and was not related to transforming growth factor beta(1) (Spearman correlation coefficients -0.565, P <.001, 0.362, P <.001, and -0.062, P =.460, respectively). However, interleukin 10 levels in patient serum after cardiopulmonary bypass were 300-fold below the quantities needed for half-maximal inhibition of tumor necrosis factor alpha synthesis in vitro. Moreover, the inhibitory activity could not be removed by immune absorption of interleukin 10. CONCLUSIONS: These results suggest that during cardiac operations cytokine-inhibitory serum activities are released or newly formed. These activities could not be explained by the actions of interleukins 4 and 10 or transforming growth factor beta(1). Although their exact nature remains undetermined, these substances may contribute to the diminished immune cell functions after cardiopulmonary bypass and thus need further characterization.

Ischemic pre-conditioning of 5 minutes but not of 10 minutes improves lung function after warm ischemia in a canine model.

BACKGROUND: Protection from reperfusion injury by ischemic pre-conditioning (IPC) before prolonged ischemia has been proven for the heart and the liver. We now assess the efficacy of IPC to protect lungs from reperfusion injury. METHODS: Eighteen foxhounds (25 to 30 kg) were anesthetized, intubated, and ventilated with a fraction of inspired oxygen of 0.3 at a volume-controlled mode to maintain arterial pCO2 of 30 to 40 mm Hg. After left thoracotomy, we performed warm ischemia for 3 hours by clamping the left hilus, and followed with 8 hours of reperfusion (control, n = 6). In the treated groups, IPC was performed either for 5 minutes followed by 15-minute reperfusion (n = 6, IPC-5), or by 2 successive cycles of 10-minute ischemia, followed by 10-minute reperfusion (n = 6, IPC-10) before prior to the 3-hours warm-ischemia period. Pulmonary compliance and gas exchange were determined separately for each lung, and we recorded pulmonary and systemic hemodynamics. We performed bronchoalveolar lavage (BAL) at the end of the experiment and determined total protein concentration as well as tumor necrosis factor alpha (TNF-alpha) mRNA expression in cell-free supernatant and in BAL cells, respectively. We also assessed the wet/dry ratio of the lung. RESULTS: In the controls, on reperfusion, we encountered a progressive deterioration of gas exchange, especially of the reperfused left lung, which we could largely avoid using the IPC-5 protocol. Similarly, pulmonary compliance steadily declined but was much better in the ICP-5 group. Parallel to the improvement of gas exchange and lung mechanics, we found less total alveolar protein content and TNF-alpha mRNA expression in BAL cells in the IPC-5 than in the controls. However, we did not find IPC-10 to be paralleled by a significant improvement of lung function. Neither IPC-5 nor IPC-10 influenced the pulmonary vascular resistance index or the fluid accumulation in the lung. CONCLUSION: The major finding of the present study was that 5 minutes of IPC improved lung function after 3 hours of warm ischemia of the lung.

IL-10 and TGF-beta differ in their regulation of aminopeptidase N/CD13 expression in monocytes.

Human monocytic cells express considerable amounts of aminopeptidase N (APN)/CD13, a transmembrane protein proposed to play a role in the modulation of kinins, neuropeptides and chemotactic mediators as well as in adhesion and cell-cell interactions. Previous studies have shown that APN/CD13 participates in antigen processing and presentation, trimming peptides protruding out of MHC class II molecules. In several inflammatory processes, macrophages have been shown to express especially high amounts of MHC class II molecules and of this peptidase. To learn more about the regulation of APN/CD13 on monocytes we investigated its expression under the influence of cytokines. Here, we report a dose- and time-dependent up-regulation of APN/CD13 mRNA and protein expression by transforming growth factor (TGF)-beta on human monocytes. To the contrary, we found IL-10 down-regulating the expression of APN/CD13 mRNA and protein. Both the regulation of the APN/CD13 protein assessed by immunofluorescence and the gene expression assessed by real-time PCR were highly correlated. Using the Dual-Luciferase reporter assay, we demonstrate that TGF-beta treatment of monocytes results in a higher activity of the APN/CD13 myeloid promoter. Our results implicate differences in the expression of the membrane peptidase APN/CD13 and therefore in the peptide-modulating ability of monocytes after exposure to these two immunosuppressive cytokines, TGF-beta and IL-10.

Plasma levels of immunoinhibitory cytokines interleukin-10 and transforming growth factor-beta in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Cardiovascular surgery with extracorporeal circulation causes a systemic inflammatory response, which can lead to organ failure and increased postoperative morbidity. Advances in knowledge about the interactions between markers of cellular and humoral immunity involved in the inflammatory response to cardiopulmonary bypass (CPB) may reduce the deleterious effects and improve the outcome for patients undergoing cardiac surgery. METHODS: To determine the release of immunoinhibiting cytokines during CPB, we measured plasma levels of interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) in 30 patients undergoing elective coronary artery bypass grafting. Arterial blood samples were collected at eight time points before, during and after CPB, using a standardized ELISA-technique. RESULTS: Plasma IL-10 and TGF-beta increased significantly after weaning off CPB (P < 0.05) and peaked respectively at time of skin closure (IL-10, 308 +/- 180 pg/ml; TGF-beta, 1860 +/- 906 pg/ml; mean peak +/-S.D.). Postoperatively, 6 h, IL-10 decreased to 19.8 +/- 9.8 pg/ml (P < 0.05) and TGF-beta decreased to 1133 +/- 547 pg/ml (P < 0.05). CONCLUSIONS: Both cytokines are major immunoregulatory factors with negative influence on T cell-mediated immunologic response. The significantly elevated levels at the end of CPB indicate that IL-10 and TGF-beta may be important factors of immunologic dysregulation following CPB.

Different expression of cytokines in survivors and non-survivors from MODS following cardiovascular surgery.

OBJECTIVE: Cardiopulmonary bypass is often associated with pathophysiological changes in form of systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS). In the present study, we investigated plasma levels of pro- and anti-inflammatory cytokines in survivors and non-survivors from MODS in the early postoperative course following open heart surgery. DESIGN: Prospective clinical study. SETTING: A University Cardiothoracic Intensive Care Unit. METHODS: Levels of cytokines (IL-6, IL-8, IL-10, IL-18, and TGF- ) and procalcitonin (PCT) were measured at the first four postoperative days in 16 adult male patients with an Apache II-score >24 and two or more organ dysfunctions after myocardial revascularization. MAIN RESULTS: All pro-inflammatory cytokines, except for IL-6, were significantly elevated in non-survivors from MODS, with peak values at the first two postoperative days. The plasma levels of immunoinhibitory cytokines showed no differences between the groups. CONCLUSIONS: The results of our study show a different expression of pro-inflammatory cytokines in survivors and non-survivors from MODS following operations with extracorporeal circulation. In addition to Apache-II score, especially IL-8, IL-18, and PCT may be used as parameters for the prognosis of patients with organ dysfunctions after cardiac surgery.