Special orthopaedic geriatrics (SOG) - a new multiprofessional care model for elderly patients in elective orthopaedic surgery: a study protocol for a prospective randomized controlled trial of a multimodal intervention in frail patients with hip and knee replacement.

BACKGROUND: Due to demographic change, the number of older people in Germany and worldwide will continue to rise in the coming decades. As a result, the number of elderly and frail patients undergoing total hip and knee arthroplasty is projected to increase significantly in the coming years. In order to reduce risk of complications and improve postoperative outcome, it can be beneficial to optimally prepare geriatric patients before orthopaedic surgery and to provide perioperative care by a multiprofessional orthogeriatric team. The aim of this comprehensive interventional study is to assess wether multimorbid patients can benefit from the new care model of special orthopaedic geriatrics (SOG) in elective total hip and knee arthroplasty. METHODS: The SOG study is a registered, monocentric, prospective, randomized controlled trial (RCT) funded by the German Federal Joint Committee (GBA). This parallel group RCT with a total of 310 patients is intended to investigate the specially developed multimodal care model for orthogeriatric patients with total hip and knee arthroplasty (intervention group), which already begins preoperatively, in comparison to the usual orthopaedic care without orthogeriatric co-management (control group). Patients ≥70 years of age with multimorbidity or generally patients ≥80 years of age due to increased vulnerability with indication for elective primary total hip and knee arthroplasty can be included in the study. Exclusion criteria are age < 70 years, previous bony surgery or tumor in the area of the joint to be treated, infection and increased need for care (care level ≥ 4). The primary outcome is mobility measured by the Short Physical Performance Battery (SPPB). Secondary outcomes are morbidity, mortality, postoperative complications, delirium, cognition, mood, frailty, (instrumental) activities of daily living, malnutrition, pain, polypharmacy, and patient reported outcome measures. Tertiary outcomes are length of hospital stay, readmission rate, reoperation rate, transfusion rate, and time to rehabilitation. The study data will be collected preoperative, postoperative day 1 to 7, 4 to 6 weeks and 3 months after surgery. DISCUSSION: Studies have shown that orthogeriatric co-management models in the treatment of hip fractures lead to significantly reduced morbidity and mortality rates. However, there are hardly any data available on the elective orthopaedic care of geriatric patients, especially in total hip and knee arthroplasty. In contrast to the care of trauma patients, optimal preoperative intervention is usually possible. TRIAL REGISTRATION: German Clinical Trials Register DRKS00024102. Registered on 19 January 2021.

[Perioperative management of ortho-geriatric knee or hip arthroplasty patients]. / Perioperatives Management orthogeriatrischer Patienten für die Endoprothetik von Knie oder Hüfte.

Due to the changing age structure of the Western population, an increase in geriatric patients in endoprosthetic care of hip and knee joints is to be expected in the future. The age-related frailty and the existing comorbidities pose great challenges for the entire treatment team. In the preoperative phase, geriatric patients should be identified as such and adjustable risk factors should be addressed prior to surgery. The primary goals of treatment are to minimize trauma from anesthesia and endoprosthetic surgery to ensure immediate postoperative mobilization of patients. At the same time, any perioperative complications, especially intensive care treatments, should be prevented. This is achieved excellently with algorithms that are well known from fast-track surgery.

Percutaneous Ablation of Hepatic Tumors Using Irreversible Electroporation: A Prospective Safety and Midterm Efficacy Study in 34 Patients.

PURPOSE: To evaluate the safety and efficacy of percutaneous irreversible electroporation (IRE) of primary and secondary liver cancer unsuitable for resection or thermal ablation. MATERIALS AND METHODS: In this prospective, single-center study, 65 malignant liver tumors (hepatocellular carcinoma, n = 33; cholangiocellular carcinoma, n = 5; colorectal cancer metastasis, n = 22; neuroendocrine cancer metastasis, n = 3; testicular cancer metastasis, n = 2) in 34 patients (27 men, 7 women; mean age, 59.4 y ± 11.2) were treated. Local recurrence-free survival (LRFS) according to the Kaplan-Meier method was evaluated after a median follow-up of 13.9 months. RESULTS: Median tumor diameter was 2.4 cm ± 1.4 (range, 0.2-7.1 cm). Of 65 tumors, 12 (18.5%) required retreatment because of incomplete ablation (n = 3) or early local recurrence (n = 9). LRFS at 3, 6, and 12 months was 87.4%, 79.8%, and 74.8%. The median time to progressive disease according to modified Response Evaluation Criteria In Solid Tumors was 15.6 months. Overall complication rate was 27.5% with six major complications and eight minor complications. Major complications included diffuse intraperitonal bleeding (n = 1), partial thrombosis of the portal vein (n = 1), and liver abscesses (n = 4). Minor complications were liver hematomas (n = 6) and clinically inapparent pneumothoraces (n = 2). CONCLUSIONS: IRE showed promising results regarding therapeutic efficacy for the percutaneous treatment of liver tumors; however, significant concerns remain regarding its safety.

Subsyndromal delirium after cardiac surgery.

OBJECTIVES: To evaluate the incidence of subsyndromal delirium (SSD) after cardiac surgery and its impact on clinical outcome. DESIGN: In this prospective study, 506 patients were screened for SSD and clinical delirium (CD) using the Intensive Care Delirium Screening Checklist. RESULTS: 150 (34%) patients were classified as having SSD and 54 (12%) patients as having CD. 2% of SSD patients developed CD. Patients' age, EuroSCORE, postoperative the Acute Physiology and Chronic Health Evaluation II, the incidences of emergency operations, and the number of aortic surgery increased from non-delirious (ND) to SSD. Intensive care unit (ICU) and hospital stays were longer in CD compared with SSD patients. ND patients did not differ from SSD patients regarding duration of ventilation, ICU stay, or hospital stay. The rate of home discharge decreased from ND over SSD to CD patients. Mortality in SSD patients did not differ from ND or CD patients. CONCLUSION: SSD showed a prevalence of 34% in patients after cardiac surgery. SSD occurred independent of CD for the majority of patients. Except for a lower rate of home discharge, the clinical outcome did not differ from that of ND patients. According to our data, SSD does not represent a preliminary or resolving stage of delirium.

A comparison of three supraglottic airway devices used by healthcare professionals during paediatric resuscitation simulation.

OBJECTIVE: The aim of this study was to determine the best airway device among the laryngeal mask, I-gel and the laryngeal tube used by healthcare professional groups with different levels of experience with paediatric airway management. METHOD: Three groups of healthcare professionals were separately provided with brief supervised training in using the three devices. Afterwards the participants were asked to place the airway device. For every participant, the positioning of each device was recorded. The success rate and timing of insertion were measured. Furthermore, each insertion was scored for the ease of insertion, clinical and fibreoptic verification of the position and successful ventilation. RESULTS: A total of 66 healthcare providers (22 paramedics, 22 nurse anaesthetists and 22 anaesthesia residents) participated in the study. The median time of insertion of both the laryngeal mask and the tube was significantly longer than for the I-gel for all professional groups (p<0.001). The success rate with the I-gel was higher than that with the laryngeal mask or tube (p<0.001). Except for the laryngeal mask, there were no differences among the professional groups regarding the fibreoptic evaluation. CONCLUSIONS: In terms of both the time required for successful placement and the rate of successful placement, the I-gel is superior to the laryngeal mask and tube in paediatric resuscitation simulations by healthcare professional groups with different levels of experience with paediatric airway management.

Hypoactive delirium after cardiac surgery as an independent risk factor for prolonged mechanical ventilation.

OBJECTIVE: The authors' intention was to evaluate the incidence of the three subtypes of delirium, the risk factors of the subtypes in cardiac surgery, and the impact of the subtypes on clinical outcomes. DESIGN: A prospective study. SETTING: A university hospital. PARTICIPANTS: A total population of 506 patients undergoing cardiac surgery was screened for delirium. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Patients undergoing cardiac surgery were screened by using the Intensive Care Delirium Screening Checklist (ICDSC) and the Richmond Agitation and Sedation Scale (RASS). Patients with hypoactive delirium were compared with nondelirious patients. Outcomes measured were the duration of mechanical ventilation and the length of stay in the intensive care unit. The overall delirium incidence was 11.6%, whereas the incidence of the hypoactive subtype was 9%. Age (odds ratio [OR] 1.04; 95% confidence interval [CI], 1.01-1.09, p = 0.02), a history of depression (OR = 3.57; 95% CI, 1.04-10.74; p = 0.03), preoperative therapy with diuretics (OR = 2.85; 95% CI, 1.36-6.35; p < 0.01), aortic clamping times (OR = 1.01; 95% CI, 1.00-1.02; p < 0.01) and blood transfusions (OR = 1.18; 95% CI, 1.05-1.34; p < 0.01) were predictors for the development of hypoactive delirium. Preoperative therapy with ß-blockers (OR = 0.32; 95% CI, 0.16-0.65; p < 0.01) and higher hemoglobin before surgery (OR = 0.73; 95% CI, 0.60-0.91; p < 0.01) were associated with a lower prevalence of hypoactive delirium. Hypoactive delirium is an independent predictor for prolonged mechanical ventilation time (OR = 1.56; 95% CI, 1.25-1.92; p < 0.01) and the length of stay in the ICU (OR = 1.42; 95% CI, 1.22-1.65, p < 0.01). CONCLUSION: Hypoactive delirium itself is a strong predictor for a longer ICU stay and a prolonged period of mechanical ventilation. Some of the risk factors related to the intraoperative and postoperative setting are suitable for preventive action.

Polymorphonuclear Cell Chemotaxis and Suicidal NETosis: Simultaneous Observation Using fMLP, PMA, H7, and Live Cell Imaging.

Chemotaxis and the formation of suicidal neutrophil extracellular traps (suicidal NETosis) are key functions of polymorphonuclear cells (PMNs). Neutrophil extracellular traps in particular are known to be significantly involved in the severity of inflammatory and immunological disorders such as rheumatoid arthritis and Crohn's disease. Therefore, detailed knowledge of PMNs is essential for analyzing the mechanisms involved in, and developing new therapies for, such diseases. To date, no standard method to analyze these cell activities has been established. This study used in vitro live cell imaging to simultaneously observe and analyze PMN functions. To demonstrate this, the effects of phorbol-12-myristat-13-acetat (PMA, 0.1-10 nM), N-formylmethionine-leucyl-phenylalanine (fMLP, 10 nM), and protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) on PMN chemotaxis and suicidal NETosis were studied. PMA (1 nM-10 nM) resulted in significant concentration-dependent behavior in chemotaxis and an earlier onset of maximum oxidative burst and NET formation of up to 44%. When adding H7, PMA-triggered PMN functions were reduced, demonstrating that all three functions rely mostly on protein kinase C (PKC) activity, while PKC is not essential for fMLP-induced PMN activity. Thus, the method here described can be used to objectively quantify PMN functions and, especially through the regulation of the PKC pathway, could be useful in further clinical studies of immunological disorders.

Flow-cytometric measurement of respiratory burst in rat polymorphonuclear granulocytes: Comparison of four cell preparation procedures, and concentration-response evaluation of soluble stimulants.

Polymorphonuclear neutrophils (PMNs) contribute to organ injury in sepsis, stroke, and other diseases. Evaluation of the oxidative burst by flow cytometry (FCM) is frequently applied to examine PMN status in humans, but rarely in rats. We established a method to assess granulocyte activation in rats by means of FCM analysis of oxidative burst. Two methods for PMN isolation involving Histopaque separation were investigated, and additionally two whole blood techniques. In addition, the concentration-response relation of the stimulants fMLP, PMA, TNF-alpha, and LPS has been determined, both as sole stimulants and for priming. A novel technique with diluted rat whole blood proved to be most appropriate for PMN preparation. One micromolar PMA and fMLP, respectively, are effective concentrations for PMN stimulation in rat whole blood. Priming with 0.1 mug/ml TNF-alpha and 1 mug/ml LPS, respectively, resulted in optimal additional stimulation. This study defined the appropriate conditions for evaluating the reactive oxygen derivate production in rat PMNs by flow cytometry. The rapid, simple, and reliable cell preparation procedure of whole blood dilution that preserves cell integrity and requires only small sample quantities. This is the first systematic dose-response evaluation of soluble stimulants of neutrophil respiratory burst in rats.

Application of three airway devices during emergency medical training by health care providers--a manikin study.

OBJECTIVE: The aim of this study was to evaluate the use of the Combitube (Kendall, Neustadt, Germany), Easytube (Rüsch, Kernen, Germany), and Laryngeal tube (VBM, Sulz, Germany) by health care providers with different experience in airway management. METHODS: This manikin study consisted of 2 sessions. In the first session, each participant received training in the use of the Combitube, Easytube, and Laryngeal tube. In the second session, each participant repeated the initial trial 4 weeks after the first session without further instruction or training. Time until successful insertion, success rate, level of education, and professional experience were recorded. RESULTS: The median time for insertion of the Combitube (P < .001) or the Easytube (P < .001) was significantly longer than for the Laryngeal tube. Success rate for the Combitube (P < .001) and the Easytube (P < .001) was lower than for the Laryngeal tube. There was no correlation between either years of professional experience and median time for successful insertion, or level of education and the number of unsuccessful insertions. Furthermore, there was no significant difference in the time for insertion between the first and the second sessions. CONCLUSION: Regarding the time required for successful placement and success rate, Laryngeal tube seems to be superior compared to Combitube and Easytube in a manikin model. The use of all 3 devices can be easily learned and is independent of previous experience in airway management. The present findings suggest good skill retention for the Laryngeal tube.

Evaluation of a new arterial pressure-based cardiac output device requiring no external calibration.

BACKGROUND: Several techniques have been discussed as alternatives to the intermittent bolus thermodilution cardiac output (COPAC) measurement by the pulmonary artery catheter (PAC). However, these techniques usually require a central venous line, an additional catheter, or a special calibration procedure. A new arterial pressure-based cardiac output (COAP) device (FloTractrade mark, Vigileotrade mark; Edwards Lifesciences, Irvine, CA, USA) only requires access to the radial or femoral artery using a standard arterial catheter and does not need an external calibration. We validated this technique in critically ill patients in the intensive care unit (ICU) using COPAC as the method of reference. METHODS: We studied 20 critically ill patients, aged 16 to 74 years (mean, 55.5 +/- 18.8 years), who required both arterial and pulmonary artery pressure monitoring. COPAC measurements were performed at least every 4 hours and calculated as the average of 3 measurements, while COAP values were taken immediately at the end of bolus determinations. Accuracy of measurements was assessed by calculating the bias and limits of agreement using the method described by Bland and Altman. RESULTS: A total of 164 coupled measurements were obtained. Absolute values of COPAC ranged from 2.80 to 10.80 l/min (mean 5.93 +/- 1.55 l/min). The bias and limits of agreement between COPAC and COAP for unequal numbers of replicates was 0.02 +/- 2.92 l/min. The percentage error between COPAC and COAP was 49.3%. The bias between percentage changes in COPAC (DeltaCOPAC) and percentage changes in COAP (DeltaCOAP) for consecutive measurements was -0.70% +/- 32.28%. COPAC and COAP showed a Pearson correlation coefficient of 0.58 (p < 0.01), while the correlation coefficient between DeltaCOPAC and DeltaCOAP was 0.46 (p < 0.01). CONCLUSION: Although the COAP algorithm shows a minimal bias with COPAC over a wide range of values in an inhomogeneous group of critically ill patients, the scattering of the data remains relative wide. Therefore, the used algorithm (V 1.03) failed to demonstrate an acceptable accuracy in comparison to the clinical standard of cardiac output determination.

Species- and concentration-dependent differences of acetyl- and butyrylcholinesterase sensitivity to physostigmine and neostigmine.

Previous and more recent studies show that cholinesterase inhibitors (ChE-Is) are an important possibility for therapeutic intervention in Alzheimer's Disease, sepsis and other inflammatory syndromes. ChE-Is maintain high levels of acetylcholine (ACh) determining beneficial effects on the disease process. Despite numerous efforts to identify the appropriate choice of agents and dose of ChE-Is, a common protocol regarding concentration- and species-dependent differences in inhibitory potency (IC 50) of clinical relevant ChE-Is is still not available. To evaluate the in vitro sensitivity of Acetyl- and Butyrylcholinesterase (AChE, BChE), we compared the concentration-response effects of physostigmine and neostigmine on cholinesterases in whole blood from rat and human. A spectrophotometrical test system based on in vitro Ellman's reagent has been used to determine the kinetic properties of clinical relevant ChE-Is. In vitro, the enzyme activity of human AChE and BChE was inhibited in a concentration-dependent manner until a residual activity of 4-6% for AChE and 20-30% for BChE (IC 50 human AChE: 0.117 ± 0.007 µM physostigmine, 0.062 ± 0.003 µM neostigmine; IC 50 human BChE: 0.373 ± 0.089 µM neostigmine; 0.059 ± 0.012 µM physostigmine). The inhibition curve of rat BChE in contrast showed no concentration-dependency for physostigmine and neostigmine (87% residual activity even at high inhibitor concentrations). Rat AChE was inhibited in a concentration-dependent manner until a residual activity of 53%. The results suggest that cholinesterases from human and rat show marked species- and inhibitor-dependent differences in sensitivity to physostigmine and neostigmine. Knowledge of such differences may be critical in assessing the possible therapeutic effects of ChE-Is in both species and may guide researchers in the optimal design of future experiments regarding the application of ChE-Is.

Geriatrics in medical students' curricula: questionnaire-based analysis.

BACKGROUND: Demographic development is accompanied by an increasingly aging society. Concerning medical education, the treatment of older people as well as the scientific research and exploration of ageing aspects in the coming years need to be considered. Aim of the study was to ascertain medical students' knowledge, interest, and attitudes regarding older patients and geriatric medicine. METHODS: Each participant completed a self-designed questionnaire. This questionnaire was based on three validated internationally recognised questionnaires ("Facts on Aging Quiz--FAQ", "Expectations Regarding Aging--ERA" and the "Aging Semantic Differential--ASD"). The inquiry and survey were performed at the beginning of the summer term in 2012 at the University of Regensburg Medical School. RESULTS: A total of n = 184/253 (72.7%) students participated in this survey. The results of the FAQ 25+ showed that respondents were able to answer an average of M = 20.4 of 36 questions (56.7%) correctly (Median, Md = 21; SD ±6.1). The personal attitudes and expectations of ageing averaged M = 41.2 points on the Likert-scale that ranged from 0 to 100 (Md = 40.4; SD ±13.7). Respondents' attitudes towards the elderly (ASD 24) averaged M = 3.5 points on the Likert-scale (range 1-7, Md 3.6, SD ±0.8). CONCLUSIONS: In our investigation, medical students' knowledge of ageing was comparable to previous surveys. Attitudes and expectations of ageing were more positive compared to previous studies. Overall, medical students expect markedly high cognitive capacities towards older people that can actively prevent cognitive impairment. However, medical students' personal interest in medicine of ageing and older people seems to be rather slight.

Modulation of immune functions in polymorphonuclear neutrophils induced by physostigmine, but not neostigmine, independent of cholinergic neurons.

BACKGROUND: Cholinesterase inhibitors (Ch-I) improve survival in experimental sepsis consistent with activation of the cholinergic-anti-inflammatory-pathway. So far, less is known about whether Ch-I have a direct immunomodulatory effect on immune cells (polymorphonuclear neutrophils, PMN) in the absence of cholinergic neurons. We investigated the concentration-response-effects of physostigmine and neostigmine on the oxidative burst activity (human and rat PMN) and the expression of adhesion molecules on the surface of human PMN under in vitro conditions. METHODS: PMN from 10 healthy humans or 10 rats were pretreated with 2, 10, 24, 97 µM physostigmine or 3, 15, 30, 150 µM neostigmine, primed with tumor-necrosis-factor-alpha (TNF-alpha) followed by stimulation with n-formyl-methionyl-leucylphenylalanine (fMLP) or stimulated with phorbol-12-myristate-13-acetate (PMA). Human and rat samples were assessed by flow cytometry for the generation of oxidative free radicals. Stimulated human PMN were additionally incubated with antibodies against Mac-1 (CD11b) or L-selectin (CD62l). RESULTS: Physostigmine and neostigmine did not alter oxidative burst activity or the expression of adhesion molecules of PMN induced by receptor-dependent activators like fMLP or TNF-alpha/fMLP (rat and human PMN, p=n.s.). Physostigmine, but not neostigmine, inhibited the protein-kinase-C-mediated oxidative burst activity by PMA in a dose-dependent manner (rat and human PMN, p<0.05). Physostigmine, in the concentration range tested, suppressed the expression of CD11b following stimulation with PMA not significantly (human PMN: control: 63.1±10.7 vs. 97 µM physostigmine: 49.9±12.8 MESF, p=n.s.). CONCLUSION: While neostigmine has no effect on functional and phenotypic changes of PMN, the lipid soluble Ch-I physostigmine causes a dose dependent reduction in PMA-induced oxidative burst, independent of neuronal released acetylcholine.

Palliative treatment of presacral recurrence of endometrial cancer using irreversible electroporation: a case report.

INTRODUCTION: Irreversible electroporation (IRE) is a new minimally invasive tumor ablation technique which induces irreversible disruption of cell membrane integrity by changing the transmembrane potential resulting in cell death. Irreversible electroporation is currently undergoing clinical investigation as local tumor therapy for malignant liver and lung lesions. This is the first case report to describe the successful palliative ablation of a presacral recurrence of an endometrial cancer to achieve locoregional tumor control and pain relief. CASE PRESENTATION: A 56-year-old Caucasian woman was referred for interventional treatment of an advanced local recurrence of endometrial cancer (11.9 × 11.6 × 14.9cm) with infiltration of the sacral bone and nerve plexus. Due to the immediate proximity to the sacral plexus, the patient could neither undergo surgical therapy nor a second radiation therapy. Due to its ablation mechanism irreversible electroporation was deemed to be the best therapy option. CONCLUSION: We showed in this case that a large tumor mass adjacent to a bundle of neural structures, the sacral plexus, can be widely ablated by irreversible electroporation with only minor temporary impairment of the neural function, even though a large infiltrating tissue volume (941cm3) was ablated.

Irreversible electroporation of a hepatocellular carcinoma lesion adjacent to a transjugular intrahepatic portosystemic shunt stent graft.

We report in a 65-year-old man hepatocellular carcinoma adjacent to a transjugular intrahepatic portosystemic shunt stent-graft which was successfully treated with irreversible electroporation (IRE). IRE is a new non-thermal tissue ablation technique which uses electrical pulses to induce cell necrosis by irreversible membrane poration. IRE proved to be more advantageous in the ablation of perivascular tumor with little injury to the surrounding structures.

Immunomodulation of neutrophil­endothelial interaction by inotropes.

OBJECTIVE: To evaluate the effect of the inotropes epinephrine, dopamine and dobutamine on expression of endothelial adhesion molecules and on neutrophil adhesion to endothelial cells under dynamic conditions. METHODS: Endothelial cells were obtained by collagenase digestion of human umbilical cord veins.Endothelial monolayers were pre-incubated with one of the chosen inotropes, with or without butoxamine, and exposed to interleukin-1. The monolayers were then incubated with fluorescencelabelled anti-human monoclonal antibodies directed against the endothelial adhesion molecules ICAM-1, E-selectin or VCAM-1. Expression of endothelial adhesion molecules was analysed by flow cytometry after pre-incubation of endothelial monolayers with one of the chosen inotropes, with or without butoxamine, and after exposure to interleukin-1. To evaluate the neutrophil adherence, the endothelium was placed on a horizontal shaker-incubator and overlayered with neutrophils. Then, non-adherent neutrophils were removed, and cells were completely dissociated. Finally, neutrophils and endothelial cells were counted by flow cytometry. RESULTS: The expression of E-selectin on endothelium following stimulation with interleukin-1 is attenuated by the inotropes dopamine or dobutamine, but not by epinephrine. The addition of butoxamine does not modify the expression of E-selectin following stimulation with interleukin-1 and pre-incubation with one of the chosen inotropes. The decrease in neutrophil adhesion to endothelium following stimulation with interleukin-1 and addition of inotropes is antagonised by the b-blocker butoxamine. CONCLUSION: In contrast to the modulation of E-selectin expression on endothelium, the effect of inotropes on neutrophil adhesion to endothelium is regulated by the expression of adhesion molecules on PMNs and mediated by the b-adrenoceptor.

Restoration of neutrophil immunocompetence after cardiopulmonary bypass by beta-adrenergic blockers.

BACKGROUND: To evaluate the possible protective effect of sympatholytic medications with respect to neutrophil function, we evaluated the influence of a nonselective beta-blocker medication on the interaction of neutrophils and epinephrine after cardiopulmonary bypass. Therefore, we studied the importance of adrenoceptors for the immunomodulation of neutrophils by catecholamines in vitro. METHODS: First, we investigated the modulation of neutrophils from healthy volunteers, after stimulation with n-formyl-l-methionyl-l-leucyl-l-phenylalanin (FMLP) in the presence of epinephrine with or without the addition of one of the following adrenergic receptor antagonists: atenolol, butoxamine, pindolol, prazosin, or RS79984. The second part included an investigation of the modulation of neutrophils from patients after operative coronary revascularization with or without extracorporeal circulation after stimulation with FMLP and addition of epinephrine. After loading with anti-CD62l or anti-CD11b antibodies or dihydrorhodamine, the expression of CD62l and CD11b and generation of oxidative free radicals were assessed by flow cytometry. RESULTS: The suppression of oxidative free radical generation, inhibition of CD62l downregulation after stimulation with FMLP, and suppression of CD11b upregulation after FMLP stimulation from epinephrine were all mediated by beta(2)-adrenoceptors. After cardiac surgery with cardiopulmonary bypass, epinephrine inhibited the CD62l downregulation, the suppression of CD11b upregulation, and the generation of oxidative free radicals after FMLP stimulation. The pre-operative administration of beta-blockers abolished the immunomodulatory effects of epinephrine on CD62l and CD11b expression and the generation of oxidative free radicals. CONCLUSION: The immunomodulatory effects of epinephrine on neutrophils remained unchanged irrespective of cardiopulmonary bypass and could contribute to the detrimental effects of epinephrine after heart surgery. The preoperative administration of nonselective beta-blockers abolished the immunomodulatory effects of epinephrine in vitro and in patients, and it enhanced the immunocompetence of neutrophils in a context of increased catecholamine levels.

Bosentan reduces oxidative burst in acid aspiration-induced lung injury in rats.

BACKGROUND: Acid aspiration induces lung injury by causing an intense inflammatory reaction. Neutrophils are attracted by various cytokines, such as TNFbeta, and release reactive oxygen species, which then cause acute lung injury. Endothelin antagonists, such as bosentan, have been found to possess anti-inflammatory properties. MATERIALS AND METHODS: We performed a prospective, randomised, controlled study to evaluate the effects of bosentan in a rat model of acid-induced lung injury. Sprague-Dawley rats underwent sevoflurane anaesthesia; lung injury was then induced by instillation of 1.2mL/kg, 0.1M hydrochloric acid. The lungs were ventilated for 6h and then randomised into three groups: bosentan 30mg/kg body weight, 90mg/kg body weight or sodium chloride, each applied immediately after acid aspiration via a gastric tube. RESULTS: After induction of acute lung inflammation, the production of reactive oxygen species by PMN following stimulation with FMLP increased significantly. Comparison of pre-treatment and post-treatment in the 90mg/kg bosentan treatment group did not show a significant increase of reactive oxygen species following stimulation with FMLP. A comparison of the absolute difference of the MESF demonstrated a significant difference between the control group and the group treated with 90mg/kg bosentan. CONCLUSIONS: Bosentan administration at 90mg/kg body weight reduced the release of reactive oxygen species after 360min in acid aspiration-induced lung injury in rats.