Acute effects of physical activity patterns on plasma cortisol and brain-derived neurotrophic factor in relation to corticospinal excitability.

Brain-derived neurotrophic factor (BDNF) and cortisol are both capable of modulating synaptic plasticity, but it is unknown how physical activity-induced changes in their plasma levels relate to corticospinal plasticity in humans. Sixteen inactive middle-aged men and women participated in three separate interventions consisting of 3 h prolonged sitting (SIT); 3 h sitting interrupted every 30 min with frequent short physical activity breaks (FPA); and 2.5 h prolonged sitting followed by 25 min of moderate intensity exercise (EXE). These 3 h sessions were each followed by a 30 min period of paired associative stimulation over the primary motor cortex (PAS). Blood samples were taken and corticospinal excitability measured at baseline, pre PAS, 5 min and 30 min post PAS. Here we report levels of plasma BDNF and cortisol over three activity conditions and relate these levels to previously published changes in corticospinal excitability of a non-activated thumb muscle. There was no interaction between time and condition in BDNF, but cortisol levels were significantly higher after EXE compared to after SIT and FPA. Higher cortisol levels at pre PAS predicted larger increases in corticospinal excitability from baseline to all subsequent time points in the FPA condition only, while levels of BDNF at pre PAS did not predict such changes in any of the conditions. Neither BDNF nor cortisol modified changes from pre PAS to the subsequent time points, suggesting that the increased corticospinal excitability was not mediated though an augmented effect of the PAS protocol. The relationship between cortisol and plasticity has been suggested to be inverted U-shaped. This is possibly why the moderately high levels of cortisol seen in the FPA condition were positively associated with changes AURC, while the higher cortisol levels seen after EXE were not. A better understanding of the mechanisms for how feasible physical activity breaks affect neuroplasticity can inform the theoretical framework for how work environments and schedules should be designed.

The effect of breaking up prolonged sitting on paired associative stimulation-induced plasticity.

Paired associative stimulation (PAS) can induce plasticity in the motor cortex, as measured by changes in corticospinal excitability (CSE). This effect is attenuated in older and less active individuals. Although a single bout of exercise enhances PAS-induced plasticity in young, physically inactive adults, it is not yet known if physical activity interventions affect PAS-induced neuroplasticity in middle-aged inactive individuals. Sixteen inactive middle-aged office workers participated in a randomized cross-over design investigating how CSE and short-interval intracortical inhibition (SICI) were affected by PAS preceded by 3 h of sitting (SIT), 3 h of sitting interrupted every 30 min by 3 min of frequent short bouts of physical activity (FPA) and 2.5 h of sitting followed by 25 min of moderate-intensity exercise (EXE). Transcranial magnetic stimulation was applied over the primary motor cortex (M1) of the dominant abductor pollicis brevis to induce recruitment curves before and 5 min and 30 min post-PAS. Linear mixed models were used to compare changes in CSE using time and condition as fixed effects and subjects as random effects. There was a main effect of time on CSE and planned within-condition comparisons showed that CSE was significantly increased from baseline to 5 min and 30 min post-PAS, in the FPA condition, with no significant changes in the SIT or EXE conditions. SICI decreased from baseline to 5 min post-PAS, but this was not related to changes in CSE. Our findings suggest that in middle-aged inactive adults, FPAs may promote corticospinal neuroplasticity. Possible mechanisms are discussed.

Scar wars.

BACKGROUND: Burn scars are common in the paediatric population. When involving the face, it diminishes quality of life. Ablative fractional laser (AFL) therapy is becoming the preferred choice for established scars due to its greater potential depth for thermal injury (4 mm), which leads to photothermolysis with subsequent neocollagenesis and collagen fibre realignment and remodelling. Combined with small z-plasties and topical steroids, it has been proven to: flatten and decrease the volume of scars, increase pliability and decrease pruritus and erythema. The purpose of the case series was to determine the clinical significance of a single session of AFL therapy, combined with small z-plasties and topical steroids on facial scars post burn injury. METHOD: Four cases of paediatric facial scarring post burns were selected to undergo a single treatment of AFL therapy, accompanied by small z-plasties and topical steroids. Modified Vancouver Scar Scores (MVSS) pre- and postoperatively at 3 and 6 months were evaluated. RESULTS: Improvement of all components of the MVSS was achieved after 6 months, with major improvement in scar pliability and symptomatology. The mean MVSS improved from 14 (range 12-16) preoperatively to 5 and 5.5 respectively at 3 and 6 months postoperatively. Non-parametric analysis with Friedman Two-Way ANOVA by Rank showed a statistical significance between the pre- and postoperative MVSS (p = 0.024). CONCLUSION: AFL should form an integral part of the burn scar armamentarium.

Progressive practice promotes motor learning and repeated transient increases in corticospinal excitability across multiple days.

BACKGROUND: A session of motor skill learning is accompanied by transient increases in corticospinal excitability(CSE), which are thought to reflect acute changes in neuronal connectivity associated with improvements in sensorimotor performance. Factors influencing changes in excitability and motor skill with continued practice remain however to be elucidated. OBJECTIVE/HYPOTHESIS: Here we investigate the hypothesis that progressive motor practice during consecutive days can induce repeated transient increases in corticospinal excitability and promote motor skill learning. METHODS: Changes in motor performance and CSE were assessed during 4 consecutive days of skill learning and 8 days after the last practice session. CSE was assessed as area under recruitment curves(RC) using transcranial magnetic stimulation(TMS). Two groups of participants(n = 12) practiced a visuomotor tracking-task with task difficulty progressively increased with individual proficiency(PPG) or with the same task level throughout all 4 days(NPPG). RESULTS: Progressive practice resulted in superior motor learning compared to NPPG(p < 0.001). Whereas NPPG displayed increased CSE following only the first day of practice(p < 0.001), progressive motor practice was accompanied by increases in CSE on both the first and the final session of motor practice(p = 0.006). Eight days after ended practice, the groups showed similar CSE, but PPG maintained superior performance at a skilled task level and transfer task performance(p < 0.005,p = 0.029). CONCLUSION: The results demonstrate that progressive practice promotes both motor learning and repeated increases in CSE across multiple days. While changes in CSE did not relate to learning our results suggest that they signify successful training. Progressive practice is thus important for optimizing neurorehabilitation and motor practice protocols in general.

Acute exercise and motor memory consolidation: Does exercise type play a role?

A single bout of high-intensity exercise can augment off-line gains in skills acquired during motor practice. It is currently unknown if the type of physical exercise influences the effect on motor skill consolidation. This study investigated the effect of three types of high-intensity exercise following visuomotor skill acquisition on the retention of motor memory in 40 young (25.3 ±3.6 years), able-bodied male participants randomly assigned to one of four groups either performing strength training (STR), circuit training (CT), indoor hockey (HOC) or rest (CON). Retention tests of the motor skill were performed 1 (R1h) and 24 h (R1d) post acquisition. For all exercise groups, mean motor performance scores decreased at R1h compared to post acquisition (POST) level; STR (P = 0.018), CT (P = 0.02), HOC (P = 0.014) and performance scores decreased for CT compared to CON (P = 0.049). Mean performance scores increased from POST to R1d for all exercise groups; STR (P = 0.010), CT (P = 0.020), HOC (P = 0.007) while performance scores for CON decreased (P = 0.043). Changes in motor performance were thus greater for STR (P = 0.006), CT (P < 0.001) and HOC (P < 0.001) compared to CON from POST to R1d. The results demonstrate that high-intensity, acute exercise can lead to a decrease in motor performance assessed shortly after motor skill practice (R1h), but enhances offline effects promoting long-term retention (R1d). Given that different exercise modalities produced similar positive off-line effects on motor memory, we conclude that exercise-induced effects beneficial to consolidation appear to depend primarily on the physiological stimulus rather than type of exercise and movements employed.

Genetic associations with viral respiratory illnesses and asthma control in children.

BACKGROUND: Viral respiratory infections can cause acute wheezing illnesses in children and exacerbations of asthma. OBJECTIVE: We sought to identify variation in genes with known antiviral and pro-inflammatory functions to identify specific associations with more severe viral respiratory illnesses and the risk of virus-induced exacerbations during the peak fall season. METHODS: The associations between genetic variation at 326 SNPs in 63 candidate genes and 10 phenotypes related to viral respiratory infection and asthma control were examined in 226 children enrolled in the RhinoGen study. Replication of asthma control phenotypes was performed in 2128 children in the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). Significant associations in RhinoGen were further validated using virus-induced wheezing illness and asthma phenotypes in an independent sample of 122 children enrolled in the Childhood Origins of Asthma (COAST) birth cohort study. RESULTS: A significant excess of P values smaller than 0.05 was observed in the analysis of the 10 RhinoGen phenotypes. Polymorphisms in 12 genes were significantly associated with variation in the four phenotypes showing a significant enrichment of small P values. Six of those genes (STAT4, JAK2, MX1, VDR, DDX58, and EIF2AK2) also showed significant associations with asthma exacerbations in the COPSAC study or with asthma or virus-induced wheezing phenotypes in the COAST study. CONCLUSIONS: We identified genetic factors contributing to individual differences in childhood viral respiratory illnesses and virus-induced exacerbations of asthma. Defining mechanisms of these associations may provide insight into the pathogenesis of viral respiratory infections and virus-induced exacerbations of asthma.

Ventilation in day care centers and sick leave among nursery children.

Several studies have reported poor indoor air quality (IAQ) in day care centers (DCCs), and other studies have shown that children attending them have an increased risk of respiratory and gastrointestinal infections. The aim of this study was to investigate whether there is an association between ventilation in DCCs and sick leave among nursery children. Data on child sick leave within an 11-week period were obtained for 635 children attending 20 DCCs. Ventilation measurements included three proxies of ventilation: air exchange rate (ACR) measured with the decay method, ACR measured by the perfluorocarbon tracer gas (PFT) method, and CO2 concentration measured over a 1-week period. All but two DCCs had balanced mechanical ventilation system, which could explain the low CO2 levels measured. The mean concentration of CO2 was 643 ppm, exceeding 1000 ppm in only one DCC. A statistically significant inverse relationship between the number of sick days and ACR measured with the decay method was found for crude and adjusted analysis, with a 12% decrease in number of sick days per hour increase in ACR measured with the decay method. This study suggests a relationship between sick leave among nursery children and ventilation in DCCs, as measured with the decay method.

Repeated treatments of drooling with botulinum toxin B in neurology.

OBJECTIVES: To investigate efficacy, saliva flow, and composition in repeated BoNT-B treatments of drooling. MATERIALS AND METHODS: Seventeen neurological patients (median 66 years), referred for treatment of drooling participated in this observational study. Median total doses of 4000 units botulinum toxin type B (BoNT-B, Neurobloc(®)) were injected with at least 3 months intervals into parotid and submandibular glands using ultrasound guidance. Measures of drooling and saliva collection for analysis were obtained before treatment, and 6, 12, and eventually 18 weeks after. RESULTS: Number of treatment series in each patient was 1-7. Compared to baseline, saliva flow rate and drooling were reduced 30-70% 6 weeks after treatment in the first series, while sodium, chloride, and total protein increased 20-80% (t-tests; P < 0.05). After 12 weeks, drooling was still significantly reduced, saliva flow tended to be, and saliva composition was back to baseline. Frequent side effects were viscous saliva and dry mouth. Due to fading effect in eight patients, individual decisions were taken to change from BoNT-B to BoNT-A. Similarly, the outcome was significantly reduced over time in six patients completing five subsequent BoNT-B treatment series (ANOVA; P < 0.05). CONCLUSION: In the first series, BoNT-B treatment resulted in marked reduction of drooling and saliva flow rate with some relapse after 12 weeks. The viscous saliva was ascribed to increased total protein content and compensatory mechanisms related to ß-adrenergic receptor-specific actions. With patients needing long-term treatment, it should be noted that the efficacy of repeated BoNT-B may fade with time.

17q21 gene variation is not associated with asthma in adulthood.

BACKGROUND: 17q21 gene variants are the strongest known genetic determinants for childhood asthma and have been reported to interact with environmental tobacco smoke exposure in childhood. It remains unclear whether individuals with 17q21 risk variants have increased risk of asthma or reduced lung function in adulthood. The aim was to examine the association between the 17q21 region and current adult asthma and lung function, and interaction with active smoking. METHODS: We investigated the single nucleotide polymorphism rs7216389 at the 17q21 locus in 3471 adults from the Health2006 cross-sectional study and in 7008 adults from The British 1958 Birth Cohort and examined the association with current asthma, spirometry measures, and related atopic traits. Analyses were performed for interaction with active smoking. RESULTS: We found no association between rs7216389[T] and asthma when meta-analyzed (OR = 1.02 [0.92-1.13], P = 0.81). The risk variant was associated with reduced FEV1 as compared to normal FEV1 (OR = 1.10 [1.01-1.12], P = 0.033) and with allergic sensitization (OR = 1.10 [1.03-1.17], P = 0.003). Individuals with rs7216389 risk variants smoked as frequently as individuals without risk variants, and there was no evidence that smoking modified the association between rs7216389 and asthma. CONCLUSION: Our study suggests that the 17q21 rs7216389 locus variant does not substantially influence asthma risk in adulthood or susceptibility to detrimental effects of active smoking. This contrasts the findings in children and suggests that this locus is associated with a childhood-specific asthma endotype.

Systemic exposure to inhaled beclometasone/formoterol DPI is age and body size dependent.

AIM: Prescription of inhaled corticosteroids to children with asthma is recommended at half the nominal dose of adults in order to reduce the risk of systemic side effects. However, there is a lack of pharmacokinetic trials supporting such dose reduction regimens. Therefore, we aimed to compare the systemic exposure to the active ingredients of a fixed dose combination of beclometasone-dipropionate (BDP) and formoterol after dry powder inhaler (DPI) administration in children, adolescents and adults. METHODS: The pharmacokinetic profiles of formoterol and beclometasone-17-monopropionate (B17MP; active metabolite of BDP) were evaluated over 8 h from two independent studies comprising children (6-11yrs, n = 27), adolescents (12-17 yrs, n = 28) and adults (≥18 yrs, n = 30) receiving a single, fixed dose of BDP/formoterol (children: 200 µg/24 µg, adolescents and adults: 400 µg/24 µg) via DPI. RESULTS: The systemic exposure (AUC) for children versus adults was almost doubled for formoterol and similar for B17MP despite the halved BDP dose administered in children. In adolescents the AUC for formoterol and B17MP were approximately one third higher than in adults for both compounds. Upon normalization for the BDP/formoterol dose in the three populations the AUC and peak concentration (C(max)) correlated inversely with age and body surface area of the patients (r ≤ -0.53; p < 0.0001). CONCLUSION: The systemic exposure to the active ingredients of BDP/formoterol administered as DPI correlates inversely with age and body size suggesting that dry powder dosage regimens should be adjusted for age and body size to avoid high systemic drug levels in children.

Genome- and transcriptome-assisted development of nuclear insertion/deletion markers for Calanus species (Copepoda: Calanoida) identification.

Copepods of the genus Calanus are key zooplankton species in temperate to arctic marine ecosystems. Despite their ecological importance, species identification remains challenging. Furthermore, the recent report of hybrids among Calanus species highlights the need for diagnostic nuclear markers to efficiently identify parental species and hybrids. Using next-generation sequencing analysis of both the genome and transcriptome from two sibling species, Calanus finmarchicus and Calanus glacialis, we developed a panel of 12 nuclear insertion/deletion markers. All the markers showed species-specific amplicon length. Furthermore, most of the markers were successfully amplified in other Calanus species, allowing the molecular identification of Calanus helgolandicus, Calanus hyperboreus and Calanus marshallae.

Deep phenotyping of the unselected COPSAC2010 birth cohort study.

BACKGROUND: We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others. OBJECTIVE: The aim of this study is to explore these interactions by conducting a longitudinal study in an unselected cohort of pregnant women and their offspring with emphasis on deep clinical phenotyping, exposure assessment, and biobanking. Exposure assessments focus on the human microbiome. Nutritional intervention during pregnancy in randomized controlled trials are included in the study to prevent disease and to be able to establish causal relationships. METHODS: Pregnant women from eastern Denmark were invited during 2008-2010 to a novel unselected 'COPSAC2010 ' cohort. The women visited the clinic during pregnancy weeks 24 and 36. Their children were followed at the clinic with deep phenotyping and collection of biological samples at nine regular visits until the age of 3 and at acute symptoms. Randomized controlled trials of high-dose vitamin D and fish oil supplements were conducted during pregnancy, and a trial of azithromycin for acute lung symptoms was conducted in the children with recurrent wheeze. RESULTS: Seven hundred and thirty-eight mothers were recruited from week 24 of gestation, and 700 of their children were included in the birth cohort. The cohort has an over-representation of atopic parents. The participant satisfaction was high and the adherence equally high with 685 children (98%) attending the 1 year clinic visit and 667 children (95%) attending the 2 year clinic visit. CONCLUSIONS: The COPSAC2010 birth cohort study provides longitudinal clinical follow-up with highly specific end-points, exposure assessments, and biobanking. The cohort has a high adherence rate promising strong data to elucidate the interaction between genomics and the exposome in perinatal life leading to lifestyle-related chronic inflammatory disorders such as asthma.

VEGFA variants are associated with pre-school lung function, but not neonatal lung function.

BACKGROUND: Vascular endothelial growth factor (VEGF) is implicated in airway remodelling and asthma development. We studied VEGFA gene variants and plasma levels and the development of lung function, bronchial hyperresponsiveness and asthma in childhood. METHODS: We analysed 13 SNPs in the VEGFA gene in 411 children from the COPSAC2000 high-risk birth cohort. Asthma was diagnosed prospectively, and lung function measurements were obtained at birth and 6 years of age. Plasma VEGF levels were measured at 18 months of age. We used a Bonferroni adjusted significance level. Findings were replicated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort at age 8. RESULTS: At age six, three SNPs from the same linkage block were associated with FEV1 (rs699947, P = 1.31E-05), independent of asthma, and there were suggestive associations between FEV1/FVC ratio and rs833052 and maximal mid-expiratory flow and rs6900017. Replication in the PIAMA cohort showed borderline association between FEV1 and rs699947 and significant meta-analysis result. SNPs upstream and nearby rs699947 were nominally associated with VEGF plasma levels. VEGF levels were not associated with asthmatic symptoms or lung function measures. CONCLUSIONS AND CLINICAL RELEVANCE: VEGF gene variants are associated with lung function at school age, but not at birth, suggesting a role of VEGF in post-natal lung function development.

Allergic rhinitis is associated with otitis media with effusion: a birth cohort study.

BACKGROUND: Childhood otitis media with effusion is a common disease and a link to allergic diseases has been suggested. OBJECTIVE: To investigate the association between atopic disease and otitis media with effusion diagnosed according to strict objective case definitions by age 6 years. METHODS: We evaluated 291 children in the 6th year of life from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) 2000 birth cohort. Otitis media with effusion was diagnosed based on tympanometric and objective evaluation. Asthma, eczema, allergic- and non-allergic rhinitis was diagnosed prospectively by pre-defined algorithms. Nasal mucosal swelling was assessed using acoustic rhinometry and nasal eosinophilia from scrapings. Analyses were performed using logistic regression and adjusted for dog, cat and smoking exposure, paternal atopy, household income, older siblings, gender and number of acute otitis media episodes. RESULTS: Otitis media with effusion was diagnosed in 39% of the cohort and was associated with allergic rhinitis (aOR = 3.36, CI = 1.26-8.96, P = 0.02), but not with nasal mucosal swelling, nasal oeosinophilia, non-allergic rhinitis, asthma or eczema. CONCLUSION: Otitis media with effusion is closely associated with allergic rhinitis presumably caused by allergic inflammation, but not mechanical nasal mucosal swelling. These findings warrant an increased awareness of otitis media with effusion in children with allergic rhinitis.

Objective assessments of allergic and nonallergic rhinitis in young children.

BACKGROUND: Allergic and nonallergic rhinitis are common childhood disorders. OBJECTIVE: To study nasal eosinophilia and nasal airway patency in young children with allergic and nonallergic rhinitis to assess the pathology behind such diagnoses. METHODS: We investigated 255 children at six years of age from the Copenhagen Prospective Study on Asthma in Childhood birth cohort assessing rhinitis history, specific immunoglobulin E relevant to rhinitis symptoms, nasal eosinophilia and nasal airway patency by acoustic rhinometry before and after decongestion. Associations were studied in a multivariate graphical model corrected for gender, height and nasal steroid usage. RESULTS: Allergic rhinitis was significantly and directly associated with irreversible nasal airway obstruction (reduced decongested nasal airway patency) (P = 0.004), whereas nonallergic rhinitis was not. Both allergic rhinitis (P = 0.000) and nonallergic rhinitis (P = 0.014) were directly and significantly associated with nasal eosinophilia, but this association was stronger for allergic rhinitis. CONCLUSION: Allergic rhinitis and nonallergic rhinitis are of different pathologies as suggested from their different associations not only to allergy but importantly also to irreversible nasal airway obstruction and eosinophilic inflammation. Allergic rhinitis was significantly associated with nasal eosinophilia and irreversible nasal airway obstruction suggesting chronic inflammation and structural remodeling of the nasal mucosa in children at the age of 6 years. Nonallergic rhinitis exhibited no change in the nasal airway patency, but some nasal mucosal eosinophilia albeit less than children with allergic rhinitis.

POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands.

The EWSR1 gene is known to play a crucial role in the development of a number of different bone and soft tissue tumours, notably Ewing's sarcoma. POU5F1 is expressed during early development to maintain the totipotent status of embryonic stem and germ cells. In the present study, we report the fusion of EWSR1 and POU5F1 in two types of epithelial tumours: hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands. This finding not only broadens considerably the spectrum of neoplasms associated with EWSR1 fusion genes but also strengthens the evidence for shared pathogenetic mechanisms in the development of adnexal and salivary gland tumours. Reminiscent of the previously reported fusion genes involving EWSR1, the identified transcript is predicted to encode a chimeric protein consisting of the EWSR1 amino-terminal domain and the POU5F1 carboxy-terminal domain. We assessed the transcriptional activation potential of the chimera compared to the wild-type proteins, as well as activation of transcription through the oct/sox composite element known to bind POU5F1. Among other POU5F1 target genes, this element is present in the promoter of NANOG and in the distal enhancer of POU5F1 itself. Our results show that although the chimera is capable of significant transcriptional activation, it may in fact convey a negative regulatory effect on target genes.

Transcriptomic and proteomic patterns of systemic inflammation in on-pump and off-pump coronary artery bypass grafting.

BACKGROUND: Coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) provides controlled operative conditions but induces a whole-body inflammatory response capable of initiating devastating morbidity and mortality. Although technically more demanding, deliberate avoidance of CPB in off-pump surgery attenuates the physiological insult associated with CABG. METHODS AND RESULTS: To systematically assess the molecular mechanisms underlying the better-preserved remote organ function, we studied gene expression patterns in leukocytes and plasma proteomic response to on-pump and off-pump CABG. Proteomic analysis confirmed (tumor necrosis factor-alpha, interleukin [IL]-6, IL-10) and expanded (eg, interferon [IFN]-gamma, granulocyte colony-stimulating factor [G-CSF], monocyte chemotactic protein-1, macrophage inflammatory protein-1beta) the mediators released on CPB, whereas blood leukocyte transcriptomics suggested that circulating leukocytes are not primarily responsible for this response. Interestingly, release of some cytokines (eg, IL-6, IFN-gamma, G-CSF) was observed on off-pump surgery to a similar extent but with delayed kinetics. A total of 45 of 4868 transcripts were identified to be significantly altered as a result of initiation of CPB. Systematic analysis of transcriptional activation by CPB revealed primarily genes involved in inflammation-related cell-cell communication (such as L-selectin or intercellular adhesion molecule-2) and signaling (such as IL-1, IL-8, or IL-18 receptors and toll-like receptors 4, 5, and 6), thus confirming a "primed" phenotype of circulating peripheral blood mononuclear cells. CONCLUSIONS: Gene array and multiplex protein analysis, only in concert, can illuminate the molecular mechanisms responsible for systemic sequelae of CPB and indicate that circulating leukocytes overexpress adhesion and signaling factors after contact with CPB, which potentially facilitates their trapping, eg, in the lungs and may promote a subsequent tissue-associated inflammatory response.

Renal effects of hypotensive anaesthesia in combination with acute normovolaemic haemodilution with hydroxyethyl starch 130/0.4 or isotonic saline.

BACKGROUND: Hypotensive anaesthesia (HA) and acute normovolaemic haemodilution (ANH) are used separately to decrease per-operative blood loss. Reducing blood viscosity by adding ANH to HA may appear profitable in a situation with lowered perfusion pressure and concern about organ ischemia. The aim of this study was to clarify the influence of HA in combination with ANH using crystalloid or colloid as replacement fluid on renal function. METHODS: Hypotensive anaesthesia was induced in 11 patients referred to major spine surgery using sevoflurane in combination with fentanyl/remifentanil. Acute normovolaemic haemodilution was carried out by drawing venous blood into standard blood bags and replacing it by isotonic saline 0.9% (Group S) or HES 130/0.4 (Group V). Renal function was evaluated before, during and up to 8 h after hypotension as the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) by means of 51Cr-EDTA and 125I-Hippuran clearances. RESULTS: Lowering mean arterial blood pressure decreased GFR and ERPF in both groups. During hypotension ERPF was lower in Group S (n = 5) than Group V (n = 6). Renal function was normalized postoperatively. We found a positive but non-significant correlation between the relative GFR change and the duration of hypotension. CONCLUSION: In conclusion, our study demonstrated that renal function, assessed by GFR and ERPF, is transiently reduced during the combination of hypotensive anaesthesia and acute normovolaemic haemodilution. A colloid-based fluid regime (HES 130/0.4) used for haemodilution may preserve renal function to a greater extent than a crystalloid-based regime (0.9% saline).

Thrombelastographic whole blood clot formation after ex vivo addition of plasma substitutes: improvements of the induced coagulopathy with fibrinogen concentrate.

BACKGROUND: Plasma substitutes such as hydroxyethyl starch (HES) and various dextrans may compromise the haemostatic system, thereby causing potentially dangerous bleeding. Whilst several mechanisms have been advanced to explain the nature of the coagulopathy induced by this colloid, there has been comparably little interest in devising ways to optimize haemostasis after a relative colloid overdose. METHODS: Real-time whole blood (WB) clot formation profiles were recorded using a thrombelastographic method employing activation with tissue factor. The coagulation tracings were transformed into dynamic velocity profiles of WB clot formation. WB from healthy individuals (n=20) was exposed to haemodilution of approximately 55% with isotonic saline, HES 200/0.5, HES 130/0.4, and dextran 70, respectively. Possible modalities for improvement of the induced coagulopathy were explored, in particular ex vivo addition of a fibrinogen concentrate. RESULTS: WB coagulation profiles changed significantly with decreased clot strength, and a compromised propagation phase of clot formation. The duration of the initiation phase of WB coagulation was unchanged. No statistical differences were detected amongst the HES solutions and dextran 70. However, dextran 70 returned a more suppressed clot development and strength compared with the HES solutions. Ex vivo haemostatic addition of washed platelets (75 x 10(9) litre(-1)) and factor VIII (0.6 IU ml(-1)) produced insignificant changes in clot initiation, propagation, and in the clot strength. In contrast, ex vivo addition of a fibrinogen concentrate (1 g litre(-1)) improved the coagulopathy induced by all of the three individual plasma expanders tested. CONCLUSION: Coagulopathy induced by haemodilution with either HES 200/0.5, HES 130/0.4, and dextran 70 may be improved by fibrinogen supplementation.