Em março de 2009, foram identificados os primeiros casos de vírus influenza A, não subtipado anteriormente e que levou a comunidade internacional a enfrentar a primeira pandemia do século XXI, na vigência do novo Regulamento Sanitário Internacional de 2005. No intervalo das semanas epidemiológicas 16 e 33, foram notificados 34.506 casos de síndrome respiratória aguda grave no Brasil. No Brasil, a maior incidência ocorreu nas faixas etárias de crianças ≤ 5 anos (3.8/100.000) e com idades entre 20-29 anos (4.6/100.000). Neste período os casos ficaram concentrados nas regiões sul e sudeste, com 94% dos casos notificados. A taxa de mortalidade na população durante este período foi 0.39/100.000 habitantes. Pessoas que apresentaram comorbidades relacionadas apresentaram o dobro de risco de evolução para o óbito, quando comparado às pessoas sem comorbidade. (RR = 1,89 IC 95% 1,64-2,18). Apesar do clima tropical, o Brasil foi um dos países mais afetados pela pandemia. No entanto, este evento está possibilitando o fortalecimento das ações de vigilância e assistência que serão úteis em todas as situações de emergências de saúde pública de importância nacional e internacional. / In March 2009, identified the first cases of a new influenza A virus, not subtyped previously. Without immunity, the international community suffered the first pandemic of the century, the term of the International Health Regulations 2005. Between epidemiological weeks 16 and 33, were reported 34,506 cases of severe acute respiratory syndrome in Brazil. In Brazil, the highest incidence occurred in younger children ≤ 5 year (3.8/100,000) and one at ages 20-29 years (4.6/100,000). Ninety-four percent of cases concentrated in two of Brazil’s five geographic regions – the south and southeast. . The mortality rate in the population during this period was 0.39/100,000 inhabitants. Cases with a reported comorbidity had approximately twice the risk of those without (RR=1.89; 95%CI 1.64 – 2.18). Despite the tropical climate, Brazil was one of the countries most affected by the pandemic. However, this event is allowing the strengthening of surveillance and assistance that will be useful in all situations of public health emergencies of national and international concern.

Orientador: Fátima Pereira de Souza / Banca: José Luiz Proença Módena / Banca: Maria Elisabete Jorge Amaral / Resumo: As infecções do trato respiratório estão associadas com mortalidade significativa no mundo inteiro e afetam principalmente crianças menores de cinco anos de idade. A maioria das infecções respiratórias é causada por agentes virais como: Vírus Sincicial Respiratório (RSV), Influenzavírus tipo A e B (FLUA e FLUB), Parainfluenza tipo 1, 2 and 3 (PIV-1, PIV-2 e PIV-3), Rhinovirus (HRV) e Metapneumovirus Humano (hMPV). O conhecimento da epidemiologia e prevalência desses vírus é importante para que metodologias terapêuticas possam ser aplicadas apropriadamente e saber como esses vírus estão circulando. O objetivo deste trabalho foi investigar a incidência de 8 tipos de vírus respiratórios em 279 amostras de aspirado nasofaríngeo obtidas de Julho/2004 a Setembro de 2005 de 120 crianças (73 do sexo masculino e 47 do sexo feminino) com idade entre 0 a 6 anos com sintomas de infecção respiratória aguda. A análise foi realizada pela técnica de RT-PCR e seqüenciamento direto. Nossos resultados mostraram que 27,2% (76/279) das amostras foram positivas para pelo um dos vírus respiratórios, sendo 84,2% (64/76) de Picornavírus, 76,3% (58/76) de Rhinovírus e 7,9% de Enterovírus (6/76), 7,9% (6/76) de RSV, 1,3% (1/76) de hMPV, 2,6% (2/76) de FLUA, 2,6% (2/76) de PIV-1 e 1,3% (1/76) de PIV-2. As infecções repetidas acometeram 29% (22/76) das crianças com infecção respiratória. A maioria das re-infecções, 82% (18/22), foram pelo gênero Rhinovírus. Os sintomas mais freqüentes foram coriza diagnosticada em 89,5% dos casos (68/76) seguido de tosse em 67,1% (51/76). Os Rhinovírus foram detectados em todo o período de estudo, com picos de infecção nos meses de inverno e outono, porém não houve associação significativa entre a presença viral e a sazonalidade. Neste estudo houve prevalência de infecção e re-infecção por Rhinovírus. Portanto, este estudo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Respiratory tract infections are associated with significant mortality worldwide and affect mostly children under five years of age. Most respiratory infections are caused by viral agents such as: Respiratory Syncytial Virus (RSV), the viruses of Influenza type A and B (FLUA and FLUB), Parainfluenza type 1, 2 and 3 (PIV-1, PIV-2 and PIV-3), Rhinovirus (HRV) and Human Metapneumovirus (hMPV). Knowledge of the epidemiology and prevalence of these viruses is important for therapeutic methods can be applied as appropriate and to know how these viruses are circulating. The aim of this work was to investigate the incidence of 8 types of respiratory viruses in 279 samples of nasopharyngeal aspirated obtained from July/2004 to September/2005 of 120 children (73 male and 47 female) with age between 0 to 6 years with symptoms of acute respiratory infection. The analysis was performed by RT-PCR and direct sequencing. Our results showed that 27,2% (76/279) of samples were positive at least for a type of the respiratory viruses, with 84,2% (64/76) of Picornaviruses, with 76,3% (58/76) of Rhinovírus e 7,9% of Enterovírus (6/76), 7,9% (6/76) of RSV, 1,3% (1/76) of hMPV, 2,6% (2/76) of FLUA, 2,6% (2/76) of PIV-1 and 1,3% (1/76) of PIV-2. The recurrent infections affect 29% (22/76) of children with respiratory infection. Most re-infections, 82% (18/22), were by Rhinovírus genus. The most frequent symptoms were runny nose diagnosed in 89.5% (68/76) followed by cough in 67.1% (51/76). Rhinovírus were detected throughout the study period, with peaks of infection during the winter and autumn, but there was no significant association between viral presence and seasonality. In this study there was prevalence of infection and re-infection by Rhinovírus. Therefore, this study provided better understanding of the circulation of respiratory viruses in a population of day care in the region... (Complete abstract click electronic access below) / Mestre

Em março de 2009, foram identificados os primeiros casos de vírus influenza A, não subtipado anteriormente e que levou a comunidade internacional a enfrentar a primeira pandemia do século XXI, na vigência do novo Regulamento Sanitário Internacional de 2005. No intervalo das semanas epidemiológicas 16 e 33, foram notificados 34.506 casos de síndrome respiratória aguda grave no Brasil. No Brasil, a maior incidência ocorreu nas faixas etárias de crianças ≤ 5 anos (3.8/100.000) e com idades entre 20-29 anos (4.6/100.000). Neste período os casos ficaram concentrados nas regiões sul e sudeste, com 94% dos casos notificados. A taxa de mortalidade na população durante este período foi 0.39/100.000 habitantes. Pessoas que apresentaram comorbidades relacionadas apresentaram o dobro de risco de evolução para o óbito, quando comparado às pessoas sem comorbidade. (RR = 1,89 IC 95% 1,64-2,18). Apesar do clima tropical, o Brasil foi um dos países mais afetados pela pandemia. No entanto, este evento está possibilitando o fortalecimento das ações de vigilância e assistência que serão úteis em todas as situações de emergências de saúde pública de importância nacional e internacional. / In March 2009, identified the first cases of a new influenza A virus, not subtyped previously. Without immunity, the international community suffered the first pandemic of the century, the term of the International Health Regulations 2005. Between epidemiological weeks 16 and 33, were reported 34,506 cases of severe acute respiratory syndrome in Brazil. In Brazil, the highest incidence occurred in younger children ≤ 5 year (3.8/100,000) and one at ages 20-29 years (4.6/100,000). Ninety-four percent of cases concentrated in two of Brazil’s five geographic regions – the south and southeast. . The mortality rate in the population during this period was 0.39/100,000 inhabitants. Cases with a reported comorbidity had approximately twice the risk of those without (RR=1.89; 95%CI 1.64 – 2.18). Despite the tropical climate, Brazil was one of the countries most affected by the pandemic. However, this event is allowing the strengthening of surveillance and assistance that will be useful in all situations of public health emergencies of national and international concern.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2015-04-23T14:59:21Z No. of bitstreams: 2 Tese - Lusmaia Damaceno Camargo Costa - 2014.pdf: 1127224 bytes, checksum: 0d8abb81e39218ff98c2ffb7471822f8 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2015-04-23T15:01:32Z (GMT) No. of bitstreams: 2 Tese - Lusmaia Damaceno Camargo Costa - 2014.pdf: 1127224 bytes, checksum: 0d8abb81e39218ff98c2ffb7471822f8 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-04-23T15:01:32Z (GMT). No. of bitstreams: 2 Tese - Lusmaia Damaceno Camargo Costa - 2014.pdf: 1127224 bytes, checksum: 0d8abb81e39218ff98c2ffb7471822f8 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-04-25 / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / Objective: to describe the prevalence of respiratory viruses in children with asthma during exacerbation and compare with those non-exacerbated and nonasthmatic children during acute respiratory infection. Methods: In this cross-sectional study nasopharyngeal aspirate/swab from children (4-14 years) was collected between August-2012 and August-2013 in a city (Goiânia) in Center-Brazil. There were 92 with exacerbated asthma (EA), 72 non-asthmatic with acute respiratory infection (ARI) in emergency room, and 61 non exacerbated asthmatic (NEA) treated in specialized clinics. The samples were tested to indirect immunofluorescence using the Respiratory Panel I (Chemicon. MA, USA) and RT-PCR kit rhinovirus. The study was approved by the ethics committee of the HC / UFG and statistical analysis performed with the SPSS v.20 software (SPSS Inc., Chicago, IL). The chi-square test was used to compare categorical variables and Kruskal-Wallis test to compare medians, pvalue< 0.05 was considered significant. Results: the sample consisted of 225 children, mostly male (59.5%) with median age of seven years. The viral prevalence was 91.1% and rhinovirus was the most commonly detected (67.6%), with no significant difference in incidence among all groups. Other viruses were identified: influenza A (13.2%), adenovirus (7.5%), influenza B (3.5%), respiratory syncytial virus (2.8%), parainfluenza 2 (2.8%) and parainfluenza 1 (2.5%). Adenovirus were more frequent in ARI (p=0.25). The EA group compared to the NEA group had cough at night (p<0.01), symptoms on exertion (p<0.01), medical visits (p<0.01) and hospitalizations for asthma (p<0.01) in the last 12 months and less use of medication (8.6%) for asthma control (p<0.01). Conclusions: the prevalence of viral detection was high (90.1%) in all patients (EA, NEA and ARI) and rhinovirus was the most prevalent agent, without differences between groups while adenovirus was more common in nonasthmatic children. Children with exacerbated asthma had parameters of uncontrolled disease in the last 12 months. Asthmatic children with nonexacerbated disease had no exacerbation although most of them had viruses in their nasopharynx, probable because of the regular use of inhaled corticosteroids. / Objetivo: descrever a prevalência de vírus respiratórios em crianças asmáticas durante exacerbação e comparar com grupo de crianças asmáticas não exacerbadas e crianças não asmáticas durante episódio de infecção respiratória aguda. Métodos: Em um estudo transversal foram realizadas coletas de aspirado/swabnasofaríngeo de crianças com idade entre 4 e 14 anos no período de agosto/2012 a agosto/2013, na cidade de Goiânia. Foram estudados 92 asmáticas exacerbadas (AE) e 72 crianças não asmáticas com sintomas de infecção respiratória aguda (IRA), atendidas em unidades de emergência em Goiânia-GO. No mesmo período, foram coletadas amostras de 61 crianças asmáticas não exacerbadas (ANE) atendidas em ambulatório especializado. As amostras foram submetidas à reação de imunofluorescência indireta utilizando o kit RespiratoryPanel I (Chemicon. MA, USA) para os vírus influenza A e B, parainfluenza 1 a 3, adenovírus e vírus sincicial respiratório e o RT-PCR para o rinovírus. O trabalho foi aprovado pelo comitê de ética do HC/UFG. A análise estatística foi realizada com o auxílio do software SPSS v.20 (SPSS Inc.; Chicago, IL) e o STATA v 12.0 (StataCorp, CollegeStation, TX, EUA). O teste qui-quadrado foi utilizado para comparar variáveis categóricas e aquelas com p<0,10 foram submetidas à análise de regressão logística. O teste de Kruskal-Wallis foi utilizado para comparar as medianas de idade. Para todos os testes, o valor de p<0,05 foi considerando significativo. Resultados: a amostra final foi constituída por 225 crianças, a maioria do sexo masculino (59,5%) e a mediana de idade foide sete anos. A prevalência de detecção viral foi 91,1% e o rinovírus foi o mais frequente (67,6%), sem diferença significativa entre os três grupos. Outros vírus identificados foram: influenza A (13,2%), adenovírus (7,5%), influenza B (3,5%), sincicial respiratório (2,8%), parainfluenza2 (2,8%) e parainfluenza 1 (2,5%). O adenovírus foi mais frequente no grupo com IRA (p=0,25). O grupo AE quando comparado ao grupo ANE apresentou mais tosse noturna (p<0,01), sintomas aos esforços (p<0,01), consultas (p<0,01) e internações por asma (p<0,01) nos últimos 12 meses e menor uso de medicamento (8,6%) para controle da asma (p<0,01). Após análise de regressão, os parâmetros consulta prévia (≥3) no último ano (p= 0,42) e ausência de uso de corticosteróide inalatório (p<0,01) permaneceram significativamente associados à exacerbação. Conclusões: prevalência de identificação viral foi elevada (91,1%) de forma homogênea entre os pacientes (AE, ANE e IRA) e o rinovírus foi o agente mais prevalente, em todos os grupos. O adenovírus esteve mais presente nas crianças não asmáticas com sintomas de infecção respiratória (IRA). As crianças exacerbadas apresentavam parâmetros de não controle da doença e menor uso de corticosteroide inalatório, enquanto as não exacerbadas, apesar de apresentarem o vírus na secreção nasofaríngea, não apresentaram exacerbação, possivelmente pelo uso regular de corticosteroide inalatório.

A malária é uma doença causada pelo parasita do gênero Plasmodium e que foi responsável por cerca de 440.000 mortes em 2015. A síndrome do desconforto respiratório agudo (SDRA) é uma das principais complicações clínicas da malária. O modelo murino DBA/2 reproduz os sinais clínicos da SDRA observados em humanos, quando infectado com o Plasmodium berghei ANKA. Além disso, altos níveis da enzima heme oxigenase 1 (HO-1) foram observados em casos de malária cerebral e em SDRA em humanos. Os nossos dados indicam que os níveis da HO-1 estão aumentados em camundongos que desenvolvem SDRA associada à malária (SDRA-AM). Adicionalmente, a droga indutora de HO-1 (hemina) aumentou a sobrevivência e preveniu a SDRA-AM. Verificou-se também uma redução na permeabilidade pulmonar e nos níveis de VEGF, além de uma melhoria nos parâmetros respiratórios em animais tratados com hemina. Assim sendo, a indução da HO-1 antes do desenvolvimento da SDRA-AM é protetora e assim, a HO-1 pode ser um alvo de novos fármacos, como forma de prevenir o desenvolvimento da SDRA-AM em humanos. / Malaria is a serious disease, caused by the parasite of the genus Plasmodium, which was responsible to 440,000 deaths in 2015. Acute lung injury/ acute respiratory distress syndrome (ALI/ARDS) is one of the main clinical complications in severe malaria. The murine model DBA/2 reproduces the clinical signs of ALI/ARDS observed in humans, when infected with Plasmodium berghei ANKA. Additionally, high levels heme oxygenase 1 (HO-1) were reported in cases of cerebral malaria and in ALI/ARDS in humans. Our data have indicated that the HO-1 levels are increased in mice that develop malaria associated ALI/ARDS (MA-ALI/ARDS). Additionally, a HO-1 inducing drug (hemin) increased the survival rate and prevented mice from developing MA-ALI/ARDS in treated mice. Also, there was a decrease in the lung permeability and in lung VEGF levels, and an amelioration of respiratory parameters. Therefore, the induction of HO-1 before the development of MA-ALI/ARDS is protective, making this enzyme a possible target of new drugs to prevent the development of MA-ALI/ARDS in humans.

Introdução: A insuficiência renal (IRen) aguda ou renal crônica podem levar a complicações respiratórias, que podem culminar com insuficiência respiratória aguda (IRpA), severa hipoxemia e alterações de mecânica respiratória (MR). O tratamento hemodialítico, pode desencadear um processo inflamatório pulmonar entretanto, a correção da hipervolemia que proporciona, pode melhorar a IRpA. O objetivo deste estudo foi avaliar a influência da hemodiálise (HD) na MR de pacientes com IRen sob ventilação mecânica invasiva (VMI). Materiais e Métodos: Pacientes com IRen, idade 18 a 75 anos, em VMI e em HD. Parâmetros analisados: clínicos gerais, laboratoriais (hemograma, gasometria arterial, função renal), características da HD e MR (complacência estática e dinâmica, e resistência do sistema respiratório). Os parâmetros foram analisados antes do início da HD e 4 horas após seu início. Resultados: (média ± DP) Foram analisados 37 pacientes, idade 51 ± 17 anos. Houve perda de peso, e melhora dos parâmetros laboratoriais (p < 0,05) exceto a PaO2 e a saturação de O2. A HD não alterou a pressão arterial e nem a MR, porém o delta da complacência dinâmica apresentou correlação com o delta de creatinina (p = 0,02). Conclusão: A HD por 4 horas não altera a MR de pacientes sob VMI. / Introduction: Renal failure (RF), acute or chronic, can induce respiratory complications that can evolve to acute respiratory failure (ARpF), hypoxemia and severe changes in respiratory mechanics (RM). Hemodialysis (HD) can produce pulmonary inflammation and worse the ARpF. On other hand, HD corrects hypervolemia and thus can improve the ARpF. The objective of this study was evaluating the HD role in RM of RF patients in use of invasive mechanical ventilation (IMV). Materials and Methods: Patients with RF, age 18 to 75 years, in use of IMV and HD. Analyzed parameters: age, gender, HD characteristics, respiratory and renal laboratory tests, and RM evaluation (static and dinamic compliance and resistence). Parameters were evaluate before HD and 4 hours after it started. Results (mean ± SD): We studied 37 patients, age 51 ± 17 years. During HD the patients lost body weight and presented an improvement in pulmonary and renal parameters (p < 0.05) except for PaO2 and arterial O2 saturation (p > 0.05). HD did not induce hemodynamic instability. There was correlation (p = 0.02) between the changes in plasma creatinine and the changes in dynamic compliance. Conclusion: HD for 4 hours did not modify respiratory mechanics in patients in use of IMV.

Abstract The purpose of this study was to develop sensitive and specific laboratory diagnostic methods for the demonstration of pneumococcal surface antigens or pneumococcus-specific antibodies in clinical samples. The work took account of epidemiological aspects of both pneumococcal disease and nasopharyngeal carriage of pneumococcus. We first compared the sensitivity of pneumococcal culture and antigen detection methods in nasopharyngeal samples in a developing country setting and then investigated the possibility of improving the sensitivity of the antigen detection by introducing an enrichment step in the procedure. — Further investigations were designed to determine the validity of pneumolysin-specific immune complex bound antibody assay as a tool for diagnosing pneumococcal ALRI in a developing country setting. Finally, we developed an enzyme immunoassay for the detection of pneumococcal capsular polysaccharide antigens, using type-specific antibodies produced in-house in rabbits through immunisation with an in-house-produced pneumococcal whole cell vaccine. The method was tested in nasopharyngeal and middle ear fluid samples. The first results indicated that antigen detection might be more sensitive than culture in demonstrating pneumococci in URT, particularly in children with prior antimicrobial therapy. Antigen detection is a feasible method for studies on pneumococci in developing countries. For type-specific demonstration of S. pneumoniae, detection of pneumococcal antigen after an enrichment step proved a sensitive method that can be applied for epidemiologic study purposes, e.g., in vaccine trials, in areas without ready access to a good microbiology laboratory. Determination of IC-bound pneumolysin IgG antibodies appears to be a useful method for species-specific diagnosis of pneumococcal infections. The results indicating pneumococcal aetiology in ALRI patients in this study compare well with the best results obtained by the use of lung aspirates. Increasing the number of serial samples improves the sensitivity of the assay, but even two samples provide more positive findings than other methods currently in routine use. Criteria of positivity need to be confirmed in subsequent larger studies with both healthy controls and patients with confirmed pneumococcal disease. It is also important to control the findings in patients with pneumonia of non-pneumococcal origin. The novel enzyme immunoassay was shown to work well with enrichment culture samples, with an almost 100% sensitivity compared with the culture. Middle ear fluid samples were too diluted for the enzyme immunoassay method used, and only 74% sensitivity compared with culture was achieved. Provided that adequate samples can be obtained, the method will be a useful complement to the current laboratory methods used to diagnose pneumococcal disease. With the existence of a broad spectrum of microbiological and immunological methods, it is imperative to seek international consensus for standard methods to demonstrate pneumococcus. Otherwise it is very difficult to compare results from different clinical studies. A WHO Working Group recently proposed a standard method for detecting upper respiratory carriage of pneumococcus, but a lot of work remains to be done in other areas of research on pneumococcal infections.

Despite the advantages of using NIV, healthcare professionals are not in agreement about precisely when to commence NIV (Elliott, Confalonieri& Nava 2002:1159; Lightowler, Wedzicha, Elliott&Ram 2003: [4]; Garpestad &Hill 2006:147), which adds to the underutilisation of NIV. The aim of this study was to collaboratively develop a clinical pathway for NIV. Two main objectives were identified, namely (i) to identify the components of a clinical pathway for NIV, and (ii) to develop a clinical pathway for NIV that can be implemented in the CCU. The research design utilised for this study was qualitative, contextual, explorative and descriptive in nature. The study consisted of three phases, namely Phase 1: Components of the clinical pathway, Phase 2: Literature control, and Phase 3: Development of the clinical pathway. The objectives of the study were met, and a clinical pathway for NIV was developed. / Dissertation (MCur)--University of Pretoria, 2011. / Nursing Science / unrestricted

Klinischer Hintergund: Patienten mit akutem Lungenversagen (Acute respiratory distress syndome, ARDS) bedürfen intensivmedizinischer Behandlung. Die maschinelle Beatmung spielt dabei eine zentrale Rolle. Um einer zusätzlichen ventilatorassoziierten Lungenschädigung (ventiator induced lung injury, VILI) vorzubeugen, wird vom ARDS network die Beatmung mit niedrigem Atemzugvolumen empfohlen. Das Zulassen von Spontanatmung und Variabilität in der Druckunterstützung sind weitere Beatmungsstrategien, welchen in verschiedenen Studien positive Effekte im Bezug auf pulmonale Entzündungsreaktion, Schädigung des Lungengewebes und Gasaustausch zugeschrieben werden. Eine weit verbreitete Form der assistierten Spontanatmung ist die druckunterstützte Beatmung (Pressure Support Ventilation, PSV), bei der jede inspiratorische Atembemühung mit stets demselben Druck unterstützt wird. Es resultiert eine relative geringe Atemvariabilität. Eine weitere häufig angewandte Form der assistierten Spontanatmung ist die proportionale Druckunterstützung (Proportional Assist Ventilation, PAV). Hier verhält sich das Maß der Druckunterstützung proportional zu den inspiratorischen Bemühungen des Patienten. Entsprechend führt PAV, abhängig von der intrinsischen Variabilität des Patienten, zu einer höheren Variabilität an Atemzugvolumen und Atemfrequenz. Eine neuere Form der assistierten Spontanatmung ist die variable druckunterstützte Beatmung (noisy PSV), welche ebenfalls die Variabilität von Atemzugvolumen und Atemfrequenz erhöht. Im Unterschied zu PAV ist die Variabilität der Druckunterstützung extrinsisch und wird durch das Beatmungsgerät vorgegeben. Fragestellung /Hypothesen: Die vorliegende Studie untersucht die Therapieeffekte von noisy PSV, PAV und PSV auf pulmonale Entzündungsreaktion, Schädigung des Lungengewebes sowie Ventilationsverteilung im ARDS-Modell Surfactant depletierter Schweinelungen. Folgende Hypothesen wurden dazu formuliert: 1. Unter Noisy PSV zeigt sich eine Umverteilung der regionalen Ventilation von ventral nach dorsal. 2. Unter Anwendung von noisy PSV kommt es zu einer geringeren Schädigung des Lungengewebes im Vergleich zu PAV und PSV. 3. Noisy PSV kann die Entzündungsreaktion gegenüber PAV und PSV senken. Material und Methoden: 24 Jungschweine mit einem mittleren Körpergewicht von 31,3 kg (26,8 – 34,4 kg) wurden anästhesiert, intubiert und mechanisch beatmet. Die Lungenschädigung wurde mittels wiederholter Kochsalzlavagen herbeigeführt bis ein stabiles Verhältnis von arteriellem Sauerstoffpartialdruck zur inspiratorischen Sauerstofffraktion von unter 200 mmHg erreicht war. Dies entspricht der Definition eines moderaten ARDS. Nach Spontanisierung der Atmung folgte die Randomisierung der Versuchstiere zu einer der drei assistierten Beatmungsmodi noisy PSV, PAV oder PSV. Die Beatmung erfolgte jeweils mit einem mittleren Atemzugvolumen von 6 ml /kg KG über einen Zeitraum von sechs Stunden. Es wurden impedanztomographische Messungen zur regionalen Ventilationsverteilung durchgeführt. Untersuchungen zur pulmonalen Entzündungsreaktion und histologischen Schädigung des Lungengewebes wurden post mortem vorgenommen Zusätzlich erfolgten Messungen zu Hämodynamik, Atemmechanik und Gasaustausch. Außerdem wurden Atemmuster und die Variabilität der Atmung analysiert. Die Ergebnisse dieser Messungen sind jedoch nicht Gegenstand dieser Dissertation und werden an anderer Stelle diskutiert. Ergebnisse: PAV, nicht jedoch noisy PSV, führte zu einer Umverteilung der regionalen Ventilation von zentral nach dorsal im Vergleich zu PSV. Für den kumulierten DAD Score ließen sich keine signifikanten Unterschiede zwischen den Gruppen nachweisen. In schwerkraftunabhängigen Lungenabschnitten zeigten sich weniger interstitielles Ödem für PAV und noisy PSV im Vergleich zu PSV sowie weniger Hämorrhagie für PAV und PSV im Vergleich zu noisy PSV. Auch ergab sich ein geringeres Maß an Überdehnung für PAV im Vergleich zu PSV. In schwerkraftabhängigen Lungenabschnitten kam es unter noisy PSV zu einer Reduktion von interstitiellem Ödem im Vergleich zu PSV. Insgesamt, für schwerkraftabhängige und schwerkraftunabhängige Regionen zusammen betrachtet, zeigten sich weniger Hämorrhagie für PAV im Vergleich zu noisy PSV sowie weniger interstitielles Ödem für PAV und noisy PSV im Vergleich zu PSV. Unabhängig von der Therapieform war weniger Hämorrhagie in schwerkraftunabhängigen im Vergleich zu schwerkraftabhängigen Lungenabschnitten zu beobachten. Für den Gehalt an mRNA für IL-1, IL-6, IL-8, TNF-α, TGF-ß, Amphiregulin und Tenascin-c im Gewebe sowie für die Konzentration TNF-α und IL-8 im Lungengewebe, TNF-α im Blutplasma sowie IL-8 in den Proben der BAL ließen sich ebenso keine signifikanten Unterschiede zwischen den Gruppen nachweisen wie für die Proteinkonzentration in der BAL-Flüssigkeit und die Wet-/Dry-Ratio des Lungengewebes. Schlussfolgerungen: In diesem Modell des akuten Lungenversagens am Schwein resultierte eine 6-stündige Beatmungstherapie mit variabler Druckunterstützung, proportionaler Druckunterstützung oder konstanter Druckunterstützung in einer vergleichbaren Schädigung des Lungengewebes ohne wesentliche Unterschiede in der Entzündungsreaktion.

Das akute Lungenversagen (Adult Respiratory Distress Syndrome: ARDS) stellt ein in der Intensivmedizin häufig auftretendes Krankheitsbild dar und weist trotz intensiver Bemühungen nach wie vor eine hohe Letalität auf. Ein wichtiger pathophysiologischer Faktor bei der mit dem ARDS verbundenen schweren Gasaustauschstörung ist der intrapulmonale Rechts-links-Shunt mit daraus resultierender Abnahme des Oxygenierungsindex. Um therapeutisch eine Verbesserung der Oxygenierung zu erreichen, wurde unter anderem von Gallart et al. ein Konzept entwickelt, bei dem durch den kombinierten Einsatz eines intravenös gegebenen pulmonalen Vasokonstriktors (Almitrine) und eines inhalativ gegebenen pulmonalen Vasodilatators (inhalatives Stickstoffmonoxid: iNO) die Shuntfraktion verkleinert wird (Gallart et al. 1998). Im Rahmen dieser Arbeit wurde die Kombination von iNO mit der intravenösen Gabe von zellfreiem Hämoglobin (Hemoglobin Based Oxygen Carrier, HBOC) als Vasokonstriktor am Tiermodell des akuten Lungenversagens hinsichtlich hämodynamischer Parameter und der arteriellen Oxygenierung untersucht. Die Ergebnisse wurden verglichen mit einer zweiten Versuchsgruppe, in der die Tiere lediglich iNO und Hydroxyethylstärke als Kontrollsubstanz erhielten. In Pilotversuchen wurden dafür ein Tiermodell des akuten Lungenversagens etabliert und die Auswirkungen der Gabe von HBOC bei vorbestehendem Lungenschaden untersucht. Anhand der durchgeführten Versuche konnte gezeigt werden, dass sich durch die HBOC-Gabe sowohl der systemische als auch der pulmonalarterielle Blutdruck signifikant erhöhte. Durch die zusätzliche Gabe von iNO ließ sich dieser Effekt antagonisieren. Ein additiver Effekt auf die arterielle Oxygenierung durch den kombinierten Einsatz von HBOC und iNO -im Vergleich zur alleinigen Gabe von iNO- war nachweisbar, die Unterschiede waren jedoch nicht signifikant. Weitere Untersuchungen werden zeigen müssen, ob sich dieser Effekt bei größerer Fallzahl als signifikant erweist, oder ob dieser tatsächlich nicht vorhanden sein sollte.