Quality of recovery scores in deep serratus anterior plane block vs. sham block in ambulatory breast cancer surgery: a randomised controlled trial.

Deep serratus anterior plane block has been widely adopted as an analgesic adjunct for patients undergoing breast surgery, but robust supporting evidence of efficacy is lacking. We randomly allocated 40 patients undergoing simple or partial mastectomy with sentinel node biopsy to receive either a pre-operative deep serratus anterior plane block (serratus group) or a placebo injection (sham group), in addition to systemic analgesia. The primary outcome measure was the quality of recovery score at discharge, as assessed by the quality of recovery-15 questionnaire at various time-points. Secondary analgesic outcomes included: pain severity; postoperative opioid consumption; opioid-related side-effects; patient satisfaction up to 7 days postoperatively; and persistent postoperative pain up to 3 months after surgery. All patients who were recruited completed the study. There were no differences in the quality of recovery-15 scores between patients in the serratus and control groups, with mean (SD) scores of 96 (14) and 102 (20) for the control and serratus groups, respectively. We were also unable to detect differences in any of the secondary analgesic outcomes examined. The addition of a deep serratus anterior plane block to systemic analgesia does not enhance quality of recovery in patients undergoing ambulatory breast cancer surgery.

Thoracic paravertebral blocks in abdominal surgery - a systematic review of randomized controlled trials.

Thoracic paravertebral blocks (TPVBs) have an extensive evidence base as part of a multimodal analgesic strategy for thoracic and breast surgery and have gained popularity with the advent of ultrasound guidance. However, this role is poorly defined in the context of abdominal surgery. We performed a systematic review of randomized controlled trials, to clarify the impact of TPVB on perioperative analgesic outcomes in adult abdominal surgery. We identified 20 published trials involving a total of 1044 patients that met inclusion criteria; however there was significant heterogeneity in terms of type of surgery, TPVB technique, comparator groups and study quality. Pain scores and opioid requirements in the early postoperative period were generally improved when compared with systemic analgesia, but there was insufficient evidence for any definitive conclusions regarding comparison with epidural analgesia or other peripheral block techniques, or the benefit of continuous TPVB techniques. The reported primary block failure rate was 2.8% and the incidence of complications was 1.2% (6/504); there were no instances of pneumothorax. TPVB therefore appears to be a promising analgesic technique for abdominal surgery in terms of efficacy and safety. But further well-designed and adequately powered studies are needed to confirm its utility, particularly with respect to other regional anaesthesia techniques.

Comparison of thromboelastometry (ROTEM®) with standard plasmatic coagulation testing in paediatric surgery.

BACKGROUND: Thromboelastometry (ROTEM(®)) might be useful to detect intraoperative coagulation disorders early in major paediatric surgery. This observational trial compares this technique to standard coagulation tests. METHODS: Intraoperative blood sampling was obtained in children undergoing elective major surgery. At each time point, standard coagulation tests [activated partial thromboplastin time (aPTT), prothrombin time (PT), and fibrinogen level] and ROTEM(®) analyses (InTEM, ExTEM, and FibTEM) were performed simultaneously by trained hospital laboratory staff. RESULTS: A total of 288 blood samples from 50 subjects were analysed. While there was a poor correlation between PT and aPTT to ExTEM clotting time (CT) and InTEM CT, respectively, a good correlation was detected between PT and aPTT to clot formation time, and a very good correlation between fibrinogen level and FibTEM assay (r=0.882, P<0.001). Notably, 64% of PT and 94% of aPTT measurements were outside the reference range, while impaired CT was observed in 13% and 6.3%, respectively. Standard coagulation test results were available after a median of 53 min [inter-quartile range (IQR): 45-63 min], whereas 10 min values of ROTEM(®) results were available online after 23 min (IQR: 21-24 min). CONCLUSIONS: PT and aPTT cannot be interchangeably used with ROTEM(®) CT. Based on the results of ROTEM(®), recommended thresholds for PT and aPTT might overestimate the need for coagulation therapy. A good correlation was found between the fibrinogen level and the FibTEM assay. In addition, ROTEM(®) offered faster turnaround times.

Comparison of air-sealing characteristics of tapered- vs. cylindrical-shaped high-volume, low-pressure tube cuffs.

BACKGROUND: This study aimed at comparing air-sealing characteristics of the new tapered-shaped tracheal tube cuffs with cylindrical tube cuffs. METHODS: Tracheal tubes with tapered-shaped polyurethane (PU) and polyvinyl chloride (PVC) cuffs as well as standard cylindrical-shaped cuffs made of PU and PVC (Covidien, Athlone, Ireland) were investigated. A tracheal model attached to a test lung was intubated, and cuffs were inflated to 10, 15, 20, 25 and 30 cm H(2)O. The test lung was ventilated with intermittent positive pressure ventilation at peak inspiratory pressures (PIPs) of 20 and 25 cm H(2)O. Air leakage was assessed by spirometry and measurement of sevoflurane concentration passing the cuff at the upper cuff border using an anaesthetic gas analyser. Experiments were repeated four times with new tracheal tubes for each run. Statistical comparisons were done using Mann-Whitney U-test with level of significance at P < 0.05. RESULTS: The tapered-shaped PVC tube cuff demonstrated a significantly lower air leakage determined by spirometry than the cylindrical-shaped cuff at both PIPs (20 and 25 cm H(2)O). Similarly, sevoflurane leakage was less with the tapered PVC cuff particularly at higher cuff pressures. With the PU cuff, reduction in air leakage by a tapered-shaped compared with a cylindrical-shaped tube cuff was not significant. CONCLUSIONS: A tapered-shaped tube cuff considerably improves air-sealing characteristics of PVC tube cuffs and allows thereby reducing cuff pressure required for sufficient ventilation. In tube cuffs made of PU that exhibits superior sealing characteristics compared with PVC, a tapered shape failed to result in a further reduction of air leakage.

Bronchoscope-assisted Tritube® placement for resection of sequential tracheal stenosis.

Symptomatic tracheal stenosis is a rare but significant complication of long-term tracheal intubation and mechanical ventilation. Airway management for tracheal resection in severe tracheal stenosis, especially sequential stenoses, requires multidisciplinary planning. A valuable method of airway management is the insertion of a small-bore, cuffed tracheal tube (Tritube®, Ventinova Medical B.V., Eindhoven, The Netherlands) in combination with flow-controlled ventilation. In this case, a patient with tracheal stenosis following prolonged ventilation required resection of the stenosed tissue. A Tritube was placed via a J-tipped guidewire inserted through the working channel of a bronchoscope. Bronchoscopic cuff visualisation along the tube in severe stenosis is impossible because of the outer diameter of the tracheal tube. In this case, we therefore estimated the position of the tube tip based on the distance from the vocal cords to the carina measured on pre-operative computed tomography imaging. During completion of the dorsal tracheal anastomosis, cross field ventilation using a conventional tracheal tube had to be started due to impeded ventilation caused by the Tritube protruding distal to the carina. In severe sequential tracheal stenosis, a small-bore tracheal tube can safely be placed by guidance with a J-tipped guidewire. However, it is important to plan a backup method of ventilation, such as cross field ventilation, prior to commencing a critical procedure.

Effect of tracheal tube cuff shape on fluid leakage across the cuff: an in vitro study.

BACKGROUND: This study compared the fluid leakage in the new 'tapered' shaped against the classic 'cylindrical' shaped tracheal tube cuffs when placed in different sized tracheas. METHODS: The 7.5 mm internal diameter (ID) tracheal tube cuffs-Tapered Seal Guard (TSG), Standard Seal Guard (SSG), Hi-Lo, Microcuff, Ruesch, and Portex Profile-were compared in an in vitro apparatus. Vertical artificial tracheas with 16, 20, and 22 mm ID were intubated, 5 ml clear water was applied above the unlubricated tube cuffs, and fluid leakage was measured up to 60 min. Data of tapered vs non-tapered tube cuffs (16 observations) were compared for each tracheal diameter using the Mann-Whitney test. RESULTS: Median (range) fluid leakage (ml) at 60 min was 2.14 (0.05-4.88), 1.14 (0.00-4.84), and 0.13 (0.00-1.32), respectively, for 16, 20, and 22 mm tracheas in the TSG tube studies when compared with 4.58 (0.44-4.88), 2.21 (0.00-4.81), and 0.00 (0.00-4.81) in the SSG tube and 4.54 (1.54-4.82), 0.90 (0.00-4.49), and 4.85 (4.40-4.99) in the Microcuff tube studies. Leakage in all polyvinylchloride (PVC) tube cuffs was almost complete (5 ml) within 5 min (P<0.001). CONCLUSIONS: The tapered PU tube cuff was as effective as the cylindrical PU cuffs in smaller tracheal diameters and was more efficient than the cylindrical Microcuff PU tube cuff in larger tracheal diameter in preventing subglottic fluid leakage across the tube cuff tested in this in vitro study. PVC tube cuffs leaked much more and faster than PU cuffs.

Electrocardiographic changes during continuous intravenous application of bupivacaine in neonatal pigs.

BACKGROUND: It is controversial as to whether T-wave elevation is caused by local anaesthetics, epinephrine, or their combination. It has been shown that T-elevation after intravascular injection of a small bupivacaine test dose is caused by epinephrine and not by bupivacaine. The aim of this study was to investigate ECG changes with higher doses of i.v. bupivacaine. METHODS: Thirty neonatal pigs were anaesthetized with sevoflurane and their tracheas intubated and artificially ventilated. Under steady-state conditions, bupivacaine was continuously infused (flow rate 3.2 ml kg(-1) min(-1)) by a syringe infusion pump through a central venous catheter. Group 1 received bupivacaine 0.125%, Group 2 bupivacaine 0.5%. The ECG was continuously printed and subsequently analysed for alterations in heart rate, ventricular de- and repolarization, and arrhythmias at 1.25, 2.5, and 5 mg kg(-1) bupivacaine infused. RESULTS: Sinus rhythm persisted in all pigs. Heart rate decreased progressively in both groups, but this was significantly more pronounced in Group 1. T-wave elevation occurred in 40% and 0% (Groups 1 and 2) at 1.25 mg kg(-1), in 80% and 0% at 2.5 mg kg(-1), and in 93% and 80% at 5 mg kg(-1) bupivacaine infused. There were significant differences between the two groups at 1.25 and 2.5 mg kg(-1) infused. CONCLUSIONS: Higher doses of i.v. infused bupivacaine can cause T-elevation. With slower injection technique, T-elevation can already be detected at lower bupivacaine doses administered.

Electrocardiographic alterations during intravascular application of three different test doses of bupivacaine and epinephrine: experimental study in neonatal pigs.

BACKGROUND: Origin of electrocardiographic (ECG) alterations during intravascular injection of local anaesthetic solutions is controversial. The aim of this study was to elucidate whether epinephrine, bupivacaine or their combination is responsible for ECG alteration. METHODS: Forty-five piglets were randomized into three groups. After induction of general anaesthesia using sevoflurane and peripheral venous cannulation, the trachea was intubated, the lungs were artificially ventilated, and anaesthesia was maintained by sevoflurane. Under steady state 0.2 ml kg(-1) and after 10 min 0.4 ml kg(-1) of one of the following three test solutions was administered i.v.: bupivacaine 0.125% (Group 1), bupivacaine 0.125%+epinephrine 1:200 000 (Group 2), and plain epinephrine 1:200,000 (Group 3). The ECG was analysed for alterations in heart rate and T-elevation. RESULTS: After injection of 0.2 or 0.4 ml kg(-1) test solution, an increase in heart rate of at least 10% was found in none of Group 1 and in all of Groups 2 and 3. After application of 0.2 ml kg(-1) test solution, T-elevation was found in 7% of Group 1 and in 93% of Groups 2 and 3. The injection of 0.4 ml kg(-1) revealed a T-elevation in 27%, 100%, and 100%, respectively, in Groups 1, 2, and 3. CONCLUSIONS: This animal model demonstrated that increases in heart rate and T-elevation in the ECG during i.v. application of a common test dose (0.2 ml kg(-1)) of bupivacaine are caused by epinephrine addition. Whether higher doses of bupivacaine alone can cause similar ECG changes or not requires further studies.

Rapid pressure compensation by automated cuff pressure controllers worsens sealing in tracheal tubes.

BACKGROUND: Cyclic redistribution of air within the cuff during respiratory pressure changes creates a self-sealing mechanism which allows tracheal sealing, despite tracheal airway pressure being above baseline cuff inflation pressure. The aim of the present study was to investigate the effect of continuous automated cuff pressure regulation on tracheal sealing during cyclic respiratory pressure changes. METHODS: In vitro tracheal sealing was studied in four different high volume-low pressure (HVLP) tracheal tube cuffs size internal diameter 8.0 and 5.0 mm in combination with a conventional pressure manometer and two different automated pressure controllers (VBM Cuff Controller; Cuff Pressure Control Tracoe). Experiments were performed at 10, 15, 20, and 25 cm H(2)O cuff pressure during intermittent positive pressure ventilation with peak inspiratory pressures of 20 and 25 cm H(2)O. Air leakage was assessed spirometrically. Experiments were performed four times with each tube brand and size with two exemplars of each of the three cuff pressure controllers. RESULTS: Owing to immediate cuff pressure correction, tracheal sealing at cuff pressure below inspiratory pressure was reduced in most of the tracheal tube cuffs, except in those with reduced sealing characteristics when using the Pressure Control Tracoe compared with the conventional pressure manometer and the VBM Cuff Controller. Tracheal sealing with the Pressure Control Tracoe comparable with the other two devices was only achieved at cuff pressures of 20 and 25 cm H(2)O. CONCLUSIONS: Automated cuff pressure controllers with rapid pressure correction interfere with the self-sealing mechanism of high sealing HVLP tube cuffs and reduce their improved sealing characteristics.

Accuracy and precision of hemoglobin point-of-care testing during major pediatric surgery.

INTRODUCTION: The aim of the study was to compare accuracy and reproducibility of four point-of-care testing (POCT) devices (GEM® Premier 3000, ABL 800 flex, GEM® OPL™, HemoCue® B-Hemoglobin) for hemoglobin (Hb) analyzes as compared with the reference laboratory method (Sysmex XE 2100) in children undergoing major surgery. METHODS: Pediatric patients undergoing craniofacial, spine, hip, or cancer surgery were included. Blood samples for Hb testing were taken at several intraoperative time points and generally withdrawn from the arterial catheter, if accessible. RESULTS: A total of 256 blood samples were taken intraoperatively from 71 pediatric patients. All POCT devices showed very small bias (maximum -0.46 g/dL) to reference method as well as very good reproducibility (maximum coefficient of variation of 0.99%). However, in two cases (HemoCue), potential clinical relevant differences were observed beyond a range of 2 g/dL. CONCLUSION: All POCT devices tested and operated by trained staff for hemoglobinometry showed reliable test results. They all allow for simple, fast, and precise bedside determination of hemoglobin concentration in the intraoperative setting.

Risks, benefits, alternatives and indications of allogenic blood transfusions.

Allogeneic red blood cell (RBC) transfusions are associated with multiple disadvantages, such as limited availability, high costs, multiple risks and side effects. In addition, large outcome studies comparing liberal (hemoglobin transfusion trigger range 9-10 g/dL) and restrictive (hemoglobin transfusion trigger range 7-9 g/dL) transfusion regimens still need to be performed for surgical patients. Different transfusion alternatives are known for the pre-, intra- and postoperative period. Autologous blood donation and erythropoietin are efficacious in the preoperative period. Intraoperatively, acute normovolemic hemodilution (ANH), cell salvage, antifibrinolytics, specific anesthetic and surgical techniques, coagulation monitoring, acceptance of minimal hemoglobin values and hopefully soon artificial oxygen carriers can reduce allogeneic RBC transfusions. In the postoperative period cell salvage, antifibrinolytics, and accepting minimal hemoglobin values represent alternatives to RBC transfusions. When treating a bleeding patient, the initial administration of crystalloids and colloids to restore and maintain normovolemia is important. RBC transfusions are recommended under the following circumstances: for hemoglobin levels <6 g/dL and for physiologic signs of inadequate oxygenation such as hemodynamic instability, oxygen extraction rate >50% and myocardial ischemia, detectable by new ST-segment depressions >0.1 mV, new ST-segment elevations >0.2 mV or new wall motion abnormalities by transesophageal echocardiography. The aim of this article is to review the efficacy, risk and side effects of RBC transfusions, to discuss transfusion alternatives and to summarize current indications for RBC transfusions. This information will help the physician to judiciously use RBC transfusions when they are indeed indicated.

Molar substitution and C2/C6 ratio of hydroxyethyl starch: influence on blood coagulation.

BACKGROUND: Development of hydroxyethyl starches (HES) with a low impact on blood coagulation but a long intravascular persistence is of clinical interest. A previous in vitro study showed that low substituted high molecular weight HES does not compromise blood coagulation more than medium molecular weight HES. In the present study we assessed the individual effects on blood coagulation of molar substitution and C2/C6 ratio of a high molecular weight HES. METHODS: Blood was obtained from 30 healthy patients undergoing elective surgery and mixed with six high molecular weight (700 kDa) HES solutions differing in their molar substitution (0.42 and 0.51) and C2/C6 ratio (2.7, 7 and 14) to achieve 20, 40 and 60% dilution. Blood coagulation was assessed by Thrombelastograph analysis (TEG) and plasma coagulation tests. Data were compared using a three-way analysis of variance model with repeated measures on the three factors. RESULTS: Higher molar substitution compromised blood coagulation most (for all TEG parameters, P<0.05). The lowest C2/C6 ratio was associated with the lowest effect on blood coagulation; r (P<0.001), angle alpha (P=0.003) and coagulation index (P<0.001). No effect on k and maximum amplitude was observed (P for both >0.50). The higher molar substitution was associated with a lesser increase in PT (P=0.007) and a greater decrease in factor VIII (P=0.010). PTT, functional and antigenic von Willebrand factors were not significantly influenced by molar substitution (P for all >0.20). No significant differences between solutions with the same molar substitution but different C2/C6 ratios were found in plasma coagulation parameters (P for all >0.05). CONCLUSIONS: TEG analysis indicates that high molecular HES with a molar substitution of 0.42 and a C2/C6 ratio of 2.7 has the lowest effect on in vitro human blood coagulation.

Allogeneic red blood cell transfusions: efficacy, risks, alternatives and indications.

Careful assessment of risks and benefits has to precede each decision on allogeneic red blood cell (RBC) transfusion. Currently, a number of key issues in transfusion medicine are highly controversial, most importantly the influence of different transfusion thresholds on clinical outcome. The aim of this article is to review current evidence on blood transfusions, to highlight 'hot topics' with respect to efficacy, outcome and risks, and to provide the reader with transfusion guidelines. In addition, a brief synopsis of transfusion alternatives will be given. Based on up-to-date information of current evidence, together with clinical knowledge and experience, the physician will be able to make transfusion decisions that bear the lowest risk for the patient.

[Perioperative blood transfusions. Value, risks, and guidelines]. / Perioperative Bluttransfusion Nutzen, Risiken und Richtlinien.

Surgical blood loss and trauma are the major causes of allogeneic blood transfusions, which still bear considerable risks. After the correction of hypovolemia, the anesthesiologist often has to deal with normovolemic anemia. The clinical relevance of this isolated decrease in hemoglobin concentration consists in an eventually compromised global or regional oxygen supply with the development of tissue hypoxia below a critical threshold. This is an individual threshold for each patient and depends on his or her capacity to compensate the decrease in blood oxygen content. Therefore, physiologic transfusion triggers should primarily be applied and not rigid numeric transfusion triggers, such as hemoglobin concentration, which do not take into account each patient's individual reserve.

Molecular weight of hydroxyethyl starch: is there an effect on blood coagulation and pharmacokinetics?

BACKGROUND: The development of hydroxyethyl starches (HES) with low impact on blood coagulation but higher volume effect compared with the currently used HES solutions is of clinical interest. We hypothesized that high molecular weight, low-substituted HES might possess these properties. METHODS: Thirty pigs were infused with three different HES solutions (20 ml kg(-1)) with the same degree of molar substitution (0.42) but different molecular weights (130, 500 and 900 kDa). Serial blood samples were taken over 24 h and blood coagulation was assessed by Thromboelastograph analysis and analysis of plasma coagulation. In addition, plasma concentration and in vivo molecular weight were determined and pharmacokinetic data were computed based on a two-compartment model. RESULTS: Thromboelastograph analysis and plasma coagulation tests did not reveal a more pronounced alteration of blood coagulation with HES 500 and HES 900 compared with HES 130. In contrast, HES 500 and HES 900 had a greater area under the plasma concentration-time curve [1542 (142) g min litre(-1), P<0.001, 1701 (321) g min litre(-1), P<0.001] than HES 130 [1156 (223) g min litre(-1)] and alpha half life (t(alpha)(1/2)) was longer for HES 500 [53.8 (8.6) min, P<0.01] and HES 900 [57.1 (12.3) min, P<0.01] than for HES 130 [39.9 (10.7) min]. Beta half life (t(beta)(1/2)), however, was similar for all three types of HES [from 332 (100) to 381 (63) min]. CONCLUSIONS: In low-substituted HES, molecular weight is not a key factor in compromising blood coagulation. The longer initial intravascular persistence of high molecular weight low-substituted HES might result in a longer lasting volume effect.

Segment-specific expression of sodium-phosphate cotransporters NaPi-IIa and -IIc and interacting proteins in mouse renal proximal tubules.

Sodium-dependent phosphate cotransport in renal proximal tubules (PTs) is heterogeneous with respect to proximal tubular segmentation (S1 vs. S3) and nephron generation (superficial vs. juxtamedullary). In the present study, S1 and S3 segments of superficial and juxtamedullary nephrons were laser-microdissected and mRNA and protein expression of the Na/Pi-cotransporters NaPi-IIa and NaPi-IIc and the PDZ proteins NHERF-1 and PDZK1 determined. Expression of NaPi-IIa mRNA decreased axially in juxtamedullary nephrons. There was no effect of dietary Pi content on NaPi-lla mRNA expression in any proximal tubular segment. The abundance of the NaPi-IIa cotransporter in the brush-border membrane showed inter- and intranephron heterogeneity and increased in response to a low-Pi diet (5 days), suggesting that up-regulation of NaPi-lla occurs via post-transcriptional mechanisms. In contrast, NaPi-IIc mRNA and protein was up-regulated by the low-Pi diet in all nephron generations analysed. NHERF-1 and PDZK1, at both mRNA and protein levels, were distributed evenly along the PTs and did not change after a low-Pi diet.

Lipopolysaccharide induces functional ICAM-1 expression in rat alveolar epithelial cells in vitro.

Lipopolysaccharide (LPS)-induced lung inflammation is known to increase pulmonary intercellular adhesion molecule-1 (ICAM-1) expression. In the present study, L2 cells, a cell line of alveolar epithelial cells, were stimulated with LPS, and ICAM-1 expression was studied. ICAM-1 protein on L2 cells peaked at 6 (38% increase; P < 0.01) and 10 (48% increase; P < 0.001) h after stimulation with Escherichia coli and Pseudomonas aeruginosa LPS, respectively. ICAM-1 mRNA expression was markedly increased, with a peak at 2-4 (E. coli) and 4-6 (P. aeruginosa) h. Adherence assays of neutrophils to LPS-stimulated L2 cells showed a threefold increase in adherence (P < 0.001). Pretreatment of the neutrophils with anti-lymphocyte function-associated antigen-1 and anti-Mac-1 antibodies reduced adherence by 54% (P < 0.001). Analysis of immunofluorescence staining for ICAM-1 showed an exclusive apical expression of ICAM-1. These results indicate that LPS upregulates functional active ICAM-1 on the apical part of the membrane in rat pneumocytes.

Hypoxia mediates increased neutrophil and macrophage adhesiveness to alveolar epithelial cells.

Leukocyte infiltration is known to play an important role in hypoxia-induced tissue damage. There is a paucity of information on the role of hypoxia in the expression of adhesion molecules on respiratory epithelial cells. The current studies focus on the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), their expression pattern on alveolar epithelial cells, and their biologic function under hypoxic conditions. Rat alveolar epithelial cells (AEC) were exposed to hypoxia for several time periods. With 5% oxygen, mRNA for ICAM-1 and VCAM-1 rose by 100%, peaking between 0.5 and 1 h. ICAM-1 and VCAM-1 protein showed an increase between 2 and 4 h. Neutrophil adherence to hypoxia-exposed AEC was enhanced by 115%. This increase was reduced by 83% with anti-ICAM-1 antibody. Adherence of alveolar macrophages to AEC increased by 118% and could be blocked by 95% with anti-VCAM-1 antibody. The present study shows for the first time an early increase of ICAM-1 and VCAM-1 expression on rat AEC under hypoxic conditions. These adhesion molecules are involved in increased adhesiveness of neutrophils and macrophages. Such responses might play an important role in the adhesion of leukocytes and macrophages to lung epithelial cells during hypoxic conditions.

Decreased alveolar oxygen induces lung inflammation.

Molecular mechanisms of the inflammatory reaction in hypoxia-induced lung injury are not well defined. Therefore, effects of alveolar hypoxia were studied in rat lungs, exposing rats to 10% oxygen over periods of 1, 2, 4, 6, and 8 h. An increase in the number of macrophages in bronchoalveolar lavage fluid of hypoxic animals was shown between 1 and 8 h. Extravasation of albumin was enhanced after 1 h and remained increased throughout the study period. NF-kappaB-binding activity as well as mRNA for TNF-alpha, macrophage inflammatory protein (MIP)-1beta, and monocyte chemoattractant protein (MCP)-1 were increased within the first 2 h of exposure to hypoxia. Hypoxia-inducible factor (HIF)-1alpha and intercellular adhesion molecule (ICAM)-1 mRNA were upregulated between 1 and 6 h. Elimination of alveolar macrophages by intratracheal application of liposome-encapsulated clodronate led to a decreased expression of NF-kappaB binding activity, HIF-1alpha, TNF-alpha, ICAM-1, and MIP-1beta. In summary, alveolar hypoxia induced macrophage recruitment, an increase in albumin leakage, and enhanced expression of inflammatory mediators, which were mainly macrophage dependent. Alveolar macrophages appear to have a prominent role in the inflammatory response in hypoxia-induced lung injury and the related upregulation of inflammatory mediators.

Role of alveolar epithelial ICAM-1 in lipopolysaccharide-induced lung inflammation.

Intercellular adhesion molecule-1 (ICAM-1) is known to play a central role in lung inflammation. Limited information, however, is available regarding the expression and biological function of ICAM-1 in the alveolar epithelial compartment. The current report analyses the expression pattern of ICAM-1 in primary cultures of rat alveolar epithelial cells (AECs) and in the rat lung following instillation of bacterial endotoxin (lipopolysaccharide (LPS)) in order to better define the role of alveolar epithelial ICAM-1. AECs stimulated in vitro with LPS were evaluated for ICAM-1 and ICAM-1 messenger ribonucleic acid content. Adherence assays with neutrophils and macrophages were performed. Endotoxin-induced ICAM-1 upregulation on AECs was demonstrated in vivo by immunofluorescence staining. In addition, the effect of intratracheally-instilled anti-ICAM-1 was assessed. Significant upregulation of ICAM-1 occurred in vitro and in vivo on AECs after LPS stimulation. Adherence assays showed a 114% increase in adhesion of neutrophils to AECs. Antibody directed against ICAM-1 reduced this adhesion by 40%. A significant reduction in the number of neutrophils in bronchoalveolar lavage fluid and whole lung was seen under airway ICAM-1 blockade. These data indicate that intercellular adhesion molecule-1 participates in the inflammatory response to lipopolysaccharide-induced lung injury in the distal airways by interacting mainly with neutrophils.