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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2009.tde-07122009-175148
Document
Author
Full name
Priscila Aikawa
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Nakagawa, Naomi Kondo (President)
Barbas, Carmen Silvia Valente
Fló, Claudia Marina
Fortes, Zuleica Bruno
Friedman, Gilberto
Title in Portuguese
Efeitos da ventilação mecânica e pressão positiva no final da expiração sobre a microcirculação mesentérica em ratos Wistar
Keywords in Portuguese
Leucócitos
Mesentério
Microcirculação
Migração e rolagem de leucócitos
Pentoxifilina
Ratos Wistar
Respiração artificial
Respiração com pressão positiva
Abstract in Portuguese
Ventilação mecânica (MV) com pressão positiva no final da expiração (PEEP) melhora a oxigenação sanguínea e oferta de oxigênio aos tecidos no tratamento da insuficiência respiratória aguda. No entanto, a pressão intratorácica elevada pode alterar o fluxo sanguíneo no mesentério que pode contribuir para complicações gastrointestinais durante a VM. Investigamos os efeitos da PEEP sobre as interações leucócito-endotélio durante a VM em ratos com pulmões normais e sem administração de fluido (Fase I) e os efeitos do volume corrente baixo (LTV) e pentoxifilina (PTX) sobre a microcirculação mesentérica (Fase II). O protocolo e resultados da Fase I são os seguintes: 44 ratos Wistar machos (~240g) foram anestesiados com pentobarbital (I.P., 50mg.kg-1) e com isoflurane inalatório (1.5-2%) após instrumentação, e aleatoriamente divididos em (1) INTACTO (somente anestesia), (2) PEEP0 (PEEP=0 cmH2O), (3) PEEP5 (PEEP=5 cmH2O), e (4) PEEP10 (PEEP=10 cmH2O). Os grupos PEEP foram submetidos à traqueostomia e VM com volume corrente de 10 ml.kg-1, frequência respiratória de 70 rpm e fração inspirada de oxigênio de 1. Após 2-h de VM, realizamos laparotomia mediana e avaliamos as interações leucócito-endotélio por meio de microscopia intravital e inflamação pumonar por meios histológicos. Não observamos alterações significantes na pressão sanguínea arterial média (PAM) entre os grupos ao longo do estudo. A pressão traqueal do grupo PEEP5 foi menor comparada com os grupos PEEP0 e PEEP10 (11, 15, e 16 cmH2O, respectivamente; p<0.05). Após 2-h de VM, não houve diferenças significantes entre os grupos INTACTO, PEEP0 e PEEP5 no número de leucócitos rollers (118±9, 127±14 e 147±26 células/10minutos, respectivamente), aderidos (3±1, 3±1 e 4±2 células/100m de comprimento de vênula, respectivamente), e migrados (2±1, 2±1 e 2±1 células/5,000m2, respectivamente) no mesentério. No entanto, PEEP10 aumentaram (p<0.05) o número de leucócitos rollers (188±15 células/10minutos), aderidos (8±1 células/100m de vênula) e migrados (12±1 células/5,000 m2). Observamos inflamação pulmonar nos grupos PEEP0 e PEEP10. O protocolo e resultados da Fase II são os seguintes: 57 ratos Wistar machos (~253g) foram anestesiados com pentobarbital (I.P., 50 mg.kg-1), submetidos a traqueostomia, anestesia inalatória com isoflurane (1.5-2%), VM com PEEP de 10 cmH2O, fração inspirada de oxigênio de 0,21, e aleatoriamente divididos em (1) LTV (7 ml.kg-1), (2) volume corrente elevado (HTV, 10 ml.kg-1), e (3) PTX (HTV+ PTX, 25 mg.kg-1). Nós registramos a PAM, mecânica respiratória e gases sanguíneos arteriais no basal e após 2-h de VM. Realizamos laparotomia mediana e avaliamos as interações leucócito-endotélio no mesentério, fluxo de artéria mesentérica (FAM), mecânica respiratória e inflamação pulmonar. Não observamos diferenças entre os grupos no basal e após 2-h em PAM (113±15 vs 109± 6 mmHg). Após 2-h de VM, o FAM foi similar em todos os grupos (12.4±2.6 ml.min-1). A pressão traqueal foi menor no grupo LTV (11.2±1.6 cmH2O) comparada com HTV (14.7±1.1 cmH2O) e PTX (14.1±2.4 cmH2O). Em todos os grupos a VM aumentou a elastância pulmonar (~22%, p<0.05) e diminuiu a resistência de vias aéreas (~10%, p<0.05). LTV e PTX apresentaram valores similares de leucócitos aderidos (5±2 e 6±4 células/100m de vênula, respectivamente), e migrados (1±1 e 2±1 células/5,000m2, respectivamente). Contrariamente, HTV aumentou o número de aderidos (14±4 leucócitos/100m de vênula, p<0.05) e migrados (9±3 células/5,000m2, p<0.05) no mesentério. O grupo HTV apresentou infiltrado neutrofílico e edema pulmonar. Em conclusão, nosso estudo mostrou que a pressão intratorácica elevada é prejudicial para a microcirculação mesentérica e pulmões no modelo experimental de ratos com pulmões normais e pressão sanguínea sistêmica estável, LTV previne alterações microcirculatórias e pulmonares, e a administração precoce de PTX atenua as interações leucócito-endotélio no mesentério e inflamação pulmonar durante a VM. Esses achados podem ter relevância na compreensão das complicações induzidas pela VM e prognóstico.
Title in English
Effects of mechanical ventilation and positive end-expiratory pressure on mesenteric microcirculation in Wistar rats
Keywords in English
Artificial ventilation
Leukocytes
Mesentery
Microcirculation
Migration and rolling
Pentoxifylline
Respiration with positive pressure
Wistar rats
Abstract in English
Mechanical ventilation (MV) with positive end expiratory pressure (PEEP) improves blood oxygenation and tissue oxygen delivery during treatment of acute respiratory failure. However, high intrathoracic pressure may alter blood flow at mesentery, which may contribute to gastrointestinal complications during MV. We investigated the effects of PEEP on mesenteric leukocyte-endothelial interactions during MV in rats with normal lungs and without fluid administration (Phase I) and the effects of low-tidal volume (LTV) and pentoxifylline (PTX) on mesenteric microcirculation (Phase II). The protocol and results of Phase I are the following: 44 male Wistar rats (~240g) were anesthetized with pentobarbital (I.P., 50mg.kg-1) and inhaled isoflurane (1.5-2%) after instrumentation, and randomly divided in (1)NAIVE (only anesthesia), (2) PEEP0 (PEEP=0 cm H2O), (3) PEEP5 (PEEP=5 cmH2O), and (4) PEEP10 (PEEP=10 cmH2O). PEEP groups were submitted to tracheostomy and MV with tidal volume of 10 ml.kg-1, respiratory rate of 70 rpm and inspired oxygen fraction of 1. After 2-hrs of MV, we performed a median laparotomy and evaluated leukocyte-endothelial interactions at the mesentery and lung inflammation by histology. We did not observe significant changes mean arterial blood pressure (MABP) among groups throughout the study. Tracheal pressure in PEEP5 was lower compared with PEEP0 and PEEP10 groups (11, 15, and 16 cmH2O, respectively; p<0.05). After 2-hrs of MV, there were no differences among NAIVE, PEEP0 e PEEP5 groups in the number of rollers (118±9, 127±14 and 147±26 cells/10 minutes, respectively), adherent leukocytes (3±1, 3±1 and 4±2 cells/100 m venule, respectively), and migrated leukocytes (2±1, 2±1 and 2±1 cells/5,000 m2, respectively) at the mesentery. However, PEEP10 increased (p<0.05) the number of rolling (188±15 cells/10min), adherent (8±1 cells/100 m) and migrated leukocytes (12±1 cells/5,000 m2). We observed lung inflammation in PEEP0 and PEEP10 groups. The protocol and results of Phase II are the following: 57 male Wistar rats (~253g) were anesthetized with pentobarbital (I.P.,50 mg.kg-1), submitted to tracheostomy, inhaled anesthesia with isoflurane (1.5-2%), MV with PEEP of 10 cmH2O, inspired oxygen fraction of 0.21, and randomly divided in (1) LTV (7 ml.kg-1), (2) High-tidal volume (HTV, 10 ml.kg-1), and (3) PTX (HTV+ PTX, 25 mg.kg-1). We registered MABP, respiratory mechanics and arterial blood gases at baseline and after 2-hrs of MV. We performed a median laparotomy and evaluated leukocyte-endothelial interactions, mesenteric artery flow (MAF), respiratory mechanics and lung inflammation. We did not observe significant differences among groups at baseline and after 2-hrs in MABP (113±15 vs 109± 6 mmHg). After 2-hrs, MAF was similar in all groups (12.4±2.6 ml.min-1). Tracheal pressure was lower in LTV (11.2±1.6 cmH2O) compared with HTV (14.7±1.1 cmH2O) and PTX (14.1±2.4 cmH2O). In all groups MV increased pulmonary elastance (22%, p<0.05) and decreased airway resistance (10%, p<0.05). LTV and PTX presented similar values of adherent (5±2 and 6±4 cells/100m venule, respectively), and migrated leukocytes (1±1 and 2±1 cells/5,000m2, respectively). On the contrary, HTV increased the number of adherent (14±4 leukocytes/100m venule, p<0.05) and migrated leukocytes (9±3 cells/5,000m2, p<0.05) in the mesentery. HTV presented lung neutrophil infiltration and edema. In conclusion, our study showed that high intrathoracic pressure is harmful to mesenteric microcirculation and lungs in the experimental model of rats with normal lungs and stable systemic blood pressure, LTV prevents microcirculatory and pulmonary alterations, and early administration of PTX attenuates leukocyte-endothelial interactions at the mesentery and lung inflammation during MV. These findings may have relevance for complications MV-induced and outcome.
 
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Publishing Date
2010-05-28
 
WARNING: The material described below relates to works resulting from this thesis or dissertation. The contents of these works are the author's responsibility.
  • AIKAWA, P., et al. Effects of different PEEP levels on mesenteric leukocyte-endothelial interactions in rats during mechanical ventilation [doi:10.1590/S1807-59322009000500012]. Clinics (USP. Impresso) [online], 2009, vol. 64, p. 443-450.
  • AIKAWA, P., et al. The effects of low-tidal volume and pentoxifylline on intestinal blood flow and leukocyte-endothelial interactions in mechanically ventilated rats [doi:10.4187/respcare.01183]. Respiratory Care [online], 2011, vol. 56, p. 1942-1949.
  • AIKAWA, P., et al. The effects of low and high tidal volume and pentoxifylline on intestinal blood flow and leukocyte-endothelial interactions in mechanically ventilated rats. In 2012 Annual Congress of the American Thoracic Society, Los Angeles, 2012. 2012 Annual Congress of the American Thoracic Society., 2012. Abstract.
  • AIKAWA, P., SANNOMIYA, P., e NAKAGAWA, N. K. Efeitos da PEEP sobre a interação-leucócito endotélio em mesentério de ratos Wistar. In XXI Reunião Anual da FESBE, Águas de Lindóia. XXI REUNIÃO ANUAL DA FESBE., 2006. Resumo.
  • NAKAGAWA, N. K., et al. Effects of positive end expiratory pressure on leukocyte-endothelial interactions at rat mesenteric microcirculation. In ATS2007 INTERNATIONAL CONFERENCE - AMERICAN THORACIC SOCIETY, San Francisco, 2007. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE.New York : Lippincot, 2007. Abstract.
  • Tatebe, E.R., et al. An animal model of sepsis in appendicitis: assessment of microcirculation. In Intech. Appendicitis. Organizador. Croacia : Intech, 2011{Volume}. cap. 1, p. 207-216.http://www.teses.usp.br/teses/disponiveis/5/5160/tde-07122009-175148/
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