Comparison of the effect of lps and pam3 on ventilated lungs

<p>Abstract</p> <p>Background</p> <p>While lipopolysaccharide (LPS) from Gram-negative bacteria has been shown to augment inflammation in ventilated lungs information on the effect of Gram-positive bacteria is lacking. Therefore the effect of LPS and a lipopetide from Gram-positive bacteria, PAM3, on ventilated lungs were investigated.</p> <p>Methods</p> <p>C57/Bl6 mice were mechanically ventilated. Sterile saline (sham) and different concentrations of LPS (1 μg and 5 μg) and PAM3 (50 nM and 200 nM) were applied intratracheally. Lung function parameters and expression of MIP-2 and TNFα as well as influx of neutrophils were measured.</p> <p>Results</p> <p>Mechanical ventilation increased resistance and decreased compliance over time. PAM3 but not LPS significantly increased resistance compared to sham challenge (P < 0.05). Both LPS and PAM3 significantly increased MIP-2 and TNFα mRNA expression compared to sham challenge (P < 0.05). The numbers of neutrophils were significantly increased after LPS at a concentration of 5 μg compared to sham (P < 0.05). PAM3 significantly increased the numbers of neutrophils at both concentrations compared to sham (P < 0.05).</p> <p>Conclusions</p> <p>These data suggest that PAM3 similar to LPS enhances ventilator-induced inflammation. Moreover, PAM3 but not LPS increases pulmonary resistance in ventilated lungs. Further studies are warranted to define the role of lipopetides in ventilator-associated lung injury.</p

Effect of low tidal volume ventilation on lung function and inflammation in mice

<p>Abstract</p> <p>Background</p> <p>A large number of studies have investigated the effects of high tidal volume ventilation in mouse models. In contrast data on very short term effects of low tidal volume ventilation are sparse. Therefore we investigated the functional and structural effects of low tidal volume ventilation in mice.</p> <p>Methods</p> <p>38 Male C57/Bl6 mice were ventilated with different tidal volumes (Vt 5, 7, and 10 ml/kg) without or with application of PEEP (2 cm H₂O). Four spontaneously breathing animals served as controls. Oxygen saturation and pulse rate were monitored. Lung function was measured every 5 min for at least 30 min. Afterwards lungs were removed and histological sections were stained for measurement of infiltration with polymorphonuclear leukocytes (PMN). Moreover, mRNA expression of macrophage inflammatory protein (MIP)-2 and tumor necrosis factor (TNF)α in the lungs was quantified using real time PCR.</p> <p>Results</p> <p>Oxygen saturation did not change significantly over time of ventilation in all groups (P > 0.05). Pulse rate dropped in all groups without PEEP during mechanical ventilation. In contrast, in the groups with PEEP pulse rate increased over time. These effects were not statistically significant (P > 0.05). Tissue damping (G) and tissue elastance (H) were significantly increased in all groups after 30 min of ventilation (P < 0.05). Only the group with a Vt of 10 ml/kg and PEEP did not show a significant increase in H (P > 0.05). Mechanical ventilation significantly increased infiltration of the lungs with PMN (P < 0.05). Expression of MIP-2 was significantly induced by mechanical ventilation in all groups (P < 0.05). MIP-2 mRNA expression was lowest in the group with a Vt of 10 ml/kg + PEEP.</p> <p>Conclusions</p> <p>Our data show that very short term mechanical ventilation with lower tidal volumes than 10 ml/kg did not reduce inflammation additionally. Formation of atelectasis and inadequate oxygenation with very low tidal volumes may be important factors. Application of PEEP attenuated inflammation.</p

Increased Expression of AQP 1 and AQP 5 in Rat Lungs Ventilated with Low Tidal Volume is Time Dependent

Background and GoalsMechanical ventilation (MV) can induce or worsen pulmonary oedema. Aquaporins (AQPs) facilitate the selective and rapid bi-directional movement of water. Their role in the development and resolution of pulmonary oedema is controversial. Our objectives are to determine if prolonged MV causes lung oedema and changes in the expression of AQP 1 and AQP 5 in rats.Methods25 male Wistar rats were subjected to MV with a tidal volume of 10 ml/kg, during 2 hours (n = 12) and 4 hours (n = 13). Degree of oedema was compared with a group of non-ventilated rats (n = 5). The expression of AQP 1 and AQP 5 were determined by western immunoblotting, measuring the amount of mRNA (previously amplified by RT-PCR) and immunohistochemical staining of AQPs 1 and 5 in lung samples from all groups.ResultsLung oedema and alveolar-capillary membrane permeability did not change during MV. AQP-5 steady state levels in the western blot were increased (p<0.01) at 2 h and 4 h of MV. But in AQP-1 expression these differences were not found. However, the amount of mRNA for AQP-1 was increased at 2 h and 4 h of MV; and for AQP 5 at 4 h of MV. These findings were corroborated by representative immunohistochemical lung samples.ConclusionIn lungs from rats ventilated with a low tidal volume the expression of AQP 5 increases gradually with MV duration, but does not cause pulmonary oedema or changes in lung permeability. AQPs may have a protective effect against the oedema induced by MV

Ensaio clínico, aberto, controlado sobre a adição de brometo de ipratrópio ao fenoterol no tratamento da crise de asma em adultos Open, controlled clinical assay of the addition of ipratropium bromide to fenoterol in the treatment of acute asthma crisis in adults

No tratamento da crise de asma, empregam-se doses repetidas de drogas b2-agonistas por via inalatória. O efeito da adição do brometo de ipratrópio (BI) ao b2-agonistas é controverso em adultos. OBJETIVO: Avaliar se adição de BI ao fenoterol, em tratamentos inalatórios repetidos, induz a maior broncodilatação, com reversibilidade da crise e alta da emergência em pacientes em crise grave de asma. LOCAL DO ESTUDO: Serviço de Pronto-Atendimento de Pneumologia, Disciplina de Pneumologia da Unifesp-Hospital São Paulo, no período de julho de 1995 a fevereiro de 1997. TIPO DE ESTUDO: Aberto, randomizado, paralelo. Alta da emergência determinada pelo VEF1 e PFE > 60% do previsto. CASUÍSTICA E MÉTODOS: Cento e vinte pacientes em crise de asma foram divididos em dois grupos (N = 60): fenoterol (F) e brometo de ipratrópio + fenoterol (BIF) com VEF1 e PFE < 50% do previsto. Cada grupo recebeu três tratamentos inalatórios, através de nebulímetro e câmara de expansão, administrados em intervalos de 30 minutos. No grupo F foram administrados 4 jatos de fenoterol (400mcg) e no grupo BIF, 160mcg de BI e 400mcg de fenoterol (4 jatos). RESULTADOS: A média (± DP) do PFE basal (F = 36 ± 7% vs. BIF = 35 ± 9% previsto) e do VEF1 basal (F = 33 ± 9% vs. BIF = 32 ± 9%). Trinta e dois pacientes no grupo F e 33 pacientes no grupo BIF tiveram alta após tratamentos inalatórios. O VEF1 e PFE ao final dos tratamentos inalatórios foram, respectivamente, F = 60 ± 13% vs. BIF = 61 ± 11% e F = 74 ± 18% vs. BIF = 77 ± 13% (NS). CONCLUSÃO: A adição de brometo de ipratrópio ao fenoterol resulta em efeito funcional insignificante e sem impacto clínico no tratamento da crise de asma em adultos.<br>Repeated dosis of inhaled b2-agonists have been used in the treatment of acute asthma. The effect of added ipratropium bromide (IB) to b2-agonist is controversial in adults. OBJECTIVE: To evaluate if addition of IB to fenoterol, in repeated doses, induces a greater bronchodilation, a greater reversion of the attack, and discharge from emergency unit in adults with acute severe asthma. SETTING: Pneumology Emergency Department, Unifesp-Hospital São Paulo, in the period from July 1995 to February 1997. TYPE OF STUDY: Open, randomized and parallel study. Discharge from the hospital: FEV1 and PEF > 60% of the predicted value. METHODS: 120 patients with FEV1 and PEF < 50% of the predicted value were divided into two groups (N = 60): fenoterol (F) and ipratropium bromide + fenoterol (IBF). Each group received inhalation treatment through a metered-dose inhaler (MDI) attached to a holding chamber, administered at 30-minute interval, for a total of three treatments. In the group F four puffs of fenoterol (400 mg) were administered, and in the IBF group, 160 mg of BI and 400 mg of fenoterol (four puffs). RESULTS: The patients did not differ from basal PEF (F = 36 ± 7% vs IBF = 35 ± 9% predicted) and basal FEV1 (F = 33 ± 9% vs IBF = 32 ± 9% predicted). Thirty-two patients of group F and 33 of group IBF were discharged from hospital after the inhalation treatment. The final FEV1 and PEF after inhalation treatments were F = 60 ± 13% vs IBF = 61 ± 11% e F = 74 ± 18% vs IBF = 77 ± 13% (NS). CONCLUSION: The addition of ipratropium bromide to fenoterol results in insignificant functional effect and without clinical impact in the treatment of acute asthma in adults