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1.
J Heart Lung Transplant ; 31(5): 531-7, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22406085

RESUMEN

BACKGROUND: This study investigated the optimal alveolar oxygen concentration and inflation pressure during ischemia that reduces lung ischemia-reperfusion injury (LIRI). METHODS: Male Sprague-Dawley rats (n = 66) underwent 150 minutes of left lung ischemia by hilar clamping at an airway inflation pressure (P) of 5 or 30 cm H(2)O and an oxygen (O) concentration of 0%, 30%, or 100% (P(5)O(0), P(5)O(30), P(5)O(100), P(30)O(0), P(30)O(30) and P(30)O(100) groups). Lungs preserved with 0% oxygen were inflated with 100% nitrogen. Measurements of arterial blood gas values, pulmonary compliance, histology, flow cytometry of bronchoalveolar lavage fluid were performed on day 2 postoperatively. RESULTS: Inflation with 30 cm H(2)O resulted in increased partial pressure of arterial oxygen (Pao(2)) and lung compliance, decreased diffuse alveolar damage, and less infiltration of CD4(+) and CD8(+) lymphocytes and major histocompatibility complex class II-positive (MHCII(+)) antigen-presenting cells (APCs) in the left lung on day 2 compared with clamping at an airway inflation pressure of 5 cm H(2)O. The 100% oxygen groups demonstrated a lower Pao(2) and a decreased pulmonary compliance than 30% oxygen groups. More CD8(+) lymphocytes and MHCII(+) APCs were found in the P(5)O(100) group than in the P(5)O(0) and P(5)O(30) groups. CONCLUSION: Alveolar inflation with a pressure of 30 cm H(2)O and an oxygen concentration of 30% decreases the severity of LIRI. The protective effect is mainly due to hyperinflation and, to a lesser extent, through oxygen concentration.


Asunto(s)
Pulmón/metabolismo , Oxígeno/metabolismo , Alveolos Pulmonares/fisiología , Daño por Reperfusión/prevención & control , Animales , Peróxido de Hidrógeno , Rendimiento Pulmonar/fisiología , Masculino , Modelos Animales , Presión Parcial , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo
2.
Anesthesiology ; 111(6): 1238-48, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19934867

RESUMEN

BACKGROUND: Acute lung injury is a common complication in critically ill patients. Several studies suggest that volatile anesthetics have immunomodulating effects. The aim of the current study was to assess possible postconditioning with sevoflurane in an in vivo model of endotoxin-induced lung injury. METHODS: Rats were anesthetized, tracheotomized, and mechanically ventilated. Lipopolysaccharide (saline as control) was administered intratracheally. Upon injury after 2 h of propofol anesthesia, general anesthesia was continued with either sevoflurane or propofol for 4 h. Arterial blood gases were measured every 2 h. After 6 h of injury, bronchoalveolar lavage was performed and lungs were collected. Total cell count, albumin content, concentrations of the cytokines cytokine-induced neutrophil chemoattractant-1 and monocyte chemoattractant protein-1, and phospholipids were analyzed in bronchoalveolar lavage fluid. Expression of messenger RNA for the two cytokines and for surfactant protein B was determined in lung tissue. Histopathologic examination of the lung was performed. RESULTS: Significant improvement of the ratio of oxygen tension to inspired oxygen fraction was shown with sevoflurane (mean + or - SD: 243 + or - 94 mmHg [32.4 kPa]) compared with propofol (88 + or - 19 mmHg [11.7 kPa]). Total cell count representing effector cell recruitment as well as albumin content as a measure of lung permeability were significantly decreased in the sevoflurane-lipopolysaccharide group compared with the propofol-lipopolysaccharide group in bronchoalveolar lavage fluid. Expression of the cytokines protein in bronchoalveolar lavage fluid as well as messenger RNA in lung tissue was significantly lower in the sevoflurane-lipopolysaccharide group compared with the propofol-lipopolysaccharide group. CONCLUSIONS: Postconditioning with sevoflurane attenuates lung damage and preserves lung function in an in vivo model of acute lung injury.


Asunto(s)
Anestésicos por Inhalación/toxicidad , Lipopolisacáridos , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/prevención & control , Éteres Metílicos/toxicidad , Intercambio Gaseoso Pulmonar/fisiología , Animales , Presión Sanguínea/fisiología , Líquido del Lavado Bronquioalveolar/química , Recuento de Células , Células Cultivadas , Quimiocina CCL2/biosíntesis , Quimiocina CCL2/genética , Quimiocina CXCL1/biosíntesis , Quimiocina CXCL1/genética , Quimiocinas/metabolismo , Células Endoteliales , Ensayo de Inmunoadsorción Enzimática , Hipercapnia/metabolismo , Enfermedades Pulmonares/patología , Masculino , Permeabilidad , Fosfolípidos/análisis , Propofol/farmacología , Arteria Pulmonar/citología , Arteria Pulmonar/efectos de los fármacos , Surfactantes Pulmonares/análisis , Surfactantes Pulmonares/aislamiento & purificación , ARN/biosíntesis , ARN/aislamiento & purificación , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sevoflurano
3.
Intensive Care Med ; 33(10): 1800-4, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17576531

RESUMEN

OBJECTIVE: A previous study in piglets with experimental pneumonia showed that reducing atelectasis by means of open lung ventilation attenuated bacterial translocation compared to conventional ventilation settings. This study examined the effect of open lung ventilation with higher than necessary positive end-expiratory pressures (PEEP) on bacterial translocation. DESIGN AND SETTING: Prospective animal study in a university-affiliated research laboratory. SUBJECTS: Thirty piglets. INTERVENTIONS: Animals were surfactant-depleted by whole-lung lavage and infected with group B streptococci. Thereafter the animals were ventilated for 5 h according to either a conventional ventilation strategy, open lung strategy, or open lung/high-PEEP strategy. Blood samples for blood gas analysis and blood bacterial counts were taken every hour. After 5 h of ventilation surviving animals were killed, and lung colony forming units and lung mechanics parameters were determined. RESULTS: All animals in both open lung groups survived but only 30% of those in the conventional ventilation group. Open lung ventilation resulted in significantly less bacterial translocation than either conventional or high-PEEP ventilation. Lung function in the conventional ventilated group was significantly less than in the two open lung groups. CONCLUSIONS: The lowest level of bacterial translocation was observed during optimal ventilation (open lung) which was achieved by using individually tailored settings. Deviation to either side can be harmful, as shown by the increased bacterial translocation during conventional and high-PEEP ventilation.


Asunto(s)
Traslocación Bacteriana , Neumonía Bacteriana/microbiología , Respiración con Presión Positiva , Animales , Animales Recién Nacidos , Recuento de Colonia Microbiana , Pulmón/microbiología , Pulmón/fisiopatología , Neumonía Bacteriana/fisiopatología , Porcinos
4.
Am J Respir Crit Care Med ; 169(9): 1046-53, 2004 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-14977624

RESUMEN

Besides being one of the mechanisms responsible for ventilator-induced lung injury, atelectasis also seems to aggravate the course of experimental pneumonia. In this study, we examined the effect of reducing the degree of atelectasis by natural modified surfactant and/or open lung ventilation on bacterial growth and translocation in a piglet model of Group B streptococcal pneumonia. After creating surfactant deficiency by whole lung lavage, intratracheal instillation of bacteria induced severe pneumonia with bacterial translocation into the blood stream, resulting in a mortality rate of almost 80%. Treatment with 300 mg/kg of exogenous surfactant before instillation of streptococci attenuated both bacterial growth and translocation and prevented clinical deterioration. This goal was also achieved by reversing atelectasis in lavaged animals via open lung ventilation. Combining both exogenous surfactant and open lung ventilation prevented bacterial translocation completely, comparable to Group B streptococci instillation into healthy animals. We conclude that exogenous surfactant and open lung ventilation attenuate bacterial growth and translocation in experimental pneumonia and that this attenuation is at least in part mediated by a reduction in atelectasis. These findings suggest that minimizing alveolar collapse by exogenous surfactant and open lung ventilation may reduce the risk of pneumonia and subsequent sepsis in ventilated patients.


Asunto(s)
Traslocación Bacteriana , Modelos Animales de Enfermedad , Neumonía Neumocócica/prevención & control , Respiración con Presión Positiva/métodos , Atelectasia Pulmonar , Surfactantes Pulmonares/uso terapéutico , Streptococcus agalactiae/fisiología , Animales , Animales Recién Nacidos , Bacteriemia/etiología , Bacteriemia/mortalidad , Líquido del Lavado Bronquioalveolar/química , Hemodinámica/efectos de los fármacos , Humanos , Recién Nacido , Neumonía Neumocócica/etiología , Neumonía Neumocócica/mortalidad , Neumonía Neumocócica/fisiopatología , Modelos de Riesgos Proporcionales , Proteínas/análisis , Atelectasia Pulmonar/complicaciones , Atelectasia Pulmonar/terapia , Intercambio Gaseoso Pulmonar/efectos de los fármacos , Proteína A Asociada a Surfactante Pulmonar/análisis , Surfactantes Pulmonares/farmacología , Distribución Aleatoria , Síndrome de Dificultad Respiratoria del Recién Nacido/etiología , Síndrome de Dificultad Respiratoria del Recién Nacido/prevención & control , Mecánica Respiratoria/efectos de los fármacos , Índice de Severidad de la Enfermedad , Cloruro de Sodio , Análisis de Supervivencia , Porcinos , Irrigación Terapéutica
5.
Am J Respir Crit Care Med ; 169(2): 201-8, 2004 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-14578214

RESUMEN

In acute respiratory distress syndrome patients, protective ventilation strategies reduce mortality and proinflammatory mediator levels. It has been suggested that some of the side effects of mechanical ventilation are caused by the excessive release of mediators capable of causing pulmonary inflammation and tissue destruction (biotrauma). Selective inhibition of this process might be used to minimize the side effects of artificial mechanical ventilation. This study was designed to identify the cell types and specific signaling mechanisms that are activated by ventilation with increased pressure/volume (overventilation). In isolated perfused mouse lungs, overventilation caused nuclear translocation of nuclear factor-kappaB (NF-kappaB) and enhanced expression of interleukin-6 mRNA in alveolar macrophages and alveolar epithelial type II cells. The phosphoinositide 3-OH kinase inhibitor Ly294002 prevented nuclear translocation of NF-kappaB and the subsequent release of interleukin-6 and macrophage inflammatory protein-2alpha in overventilated but not in endotoxic lungs. Similar results were obtained in rats in vivo, where Ly294002 prevented NF-kappaB activation by overventilation but not by endotoxin. These findings show that alveolar macrophages and alveolar epithelial type II cells contribute to the ventilation-induced release of proinflammatory mediators and that selective inhibition of this process is possible without inhibiting the activation of NF-kappaB by endotoxin.


Asunto(s)
Fosfatidilinositol 3-Quinasas/fisiología , Respiración Artificial/efectos adversos , Síndrome de Dificultad Respiratoria/fisiopatología , Animales , Quimiocina CXCL2 , Cromonas/farmacología , Activación Enzimática , Técnicas In Vitro , Mediadores de Inflamación/fisiología , Interleucina-6/metabolismo , Ratones , Monocinas/metabolismo , Morfolinas/farmacología , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Ratas , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/metabolismo , Síndrome de Dificultad Respiratoria/prevención & control , Transducción de Señal , Volumen de Ventilación Pulmonar
6.
Acta Pharmacol Sin ; 24(12): 1304-7, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14653963

RESUMEN

Every year, millions of patients worldwide receive ventilator support during surgery. Mechanical ventilation has become an important therapy in the treatment of patients with impaired pulmonary function and particularly in patients suffering from adult respiratory distress syndrome (ARDS). ARDS is caused by multiple factors and is characterized by respiratory dysfunction including hypoxemia and decreased lung compliance. It is known that the decrease in lung distensibility is due to a disturbed surfactant system with an elevated surface tension. This increase in surface tension leads to an increase in forces acting at the air-liquid interface, resulting finally in end-expiratory collapse, atelectasis, an increase in right-to-left shunt and a decrease in paO2.


Asunto(s)
Respiración con Presión Positiva , Síndrome de Dificultad Respiratoria/terapia , Animales , Humanos , Síndrome de Dificultad Respiratoria/fisiopatología , Mecánica Respiratoria
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