Intensive care medicine experimental
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Intensive Care Med Exp · Dec 2014
Genetic and pharmacologic inhibition of Tpl2 kinase is protective in a mouse model of ventilator-induced lung injury.
Mechanical stress induced by injurious ventilation leads to pro-inflammatory cytokine production and lung injury. The extracellular-signal-regulated-kinase, ERK1/2, participates in the signaling pathways activated upon mechanical stress in the lungs to promote the inflammatory response. Tumor progression locus 2 (Tpl2) is a MAP3kinase that activates ERK1/2 upon cytokine or TLR signaling, to induce pro-inflammatory cytokine production. The role of Tpl2 in lung inflammation, and specifically in the one caused by mechanical stress has not been investigated. The aim of the study was to examine if genetic or pharmacologic inhibition of Tpl2 could ameliorate ventilator-induced lung injury. ⋯ Genetic and pharmacologic inhibition of Tpl2 is protective in a mouse model of ventilator-induced lung injury, ameliorating both high-permeability pulmonary edema and lung inflammation.
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Intensive Care Med Exp · Dec 2014
A novel echocardiographic imaging technique, intracatheter echocardiography, to guide veno-venous extracorporeal membrane oxygenation cannulae placement in a validated ovine model.
Echocardiography plays a fundamental role in cannulae insertion and positioning for extracorporeal membrane oxygenation (ECMO). Optimal access and return cannulae orientation is required to prevent recirculation. The aim of this study was to compare a novel imaging technique, intracatheter echocardiography (iCATHe), with conventional intracardiac echocardiography (ICE) to guide placement of ECMO access and return venous cannulae. ⋯ iCATHe is a safe and feasible imaging technique to guide real-time VV ECMO cannulae placement and improves accuracy of return cannula positioning compared to ICE.
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Intensive Care Med Exp · Dec 2014
Effect of PEEP on breath sound power spectra in experimental lung injury.
Acute lung injury (ALI) is known to be associated with the emergence of inspiratory crackles and enhanced transmission of artificial sounds from the airway opening to the chest wall. Recently, we described the effect of ALI on the basic flow-induced breath sounds, separated from the crackles. In this study, we investigated the effects of positive end-expiratory pressure (PEEP) on these noncrackling basic lung sounds augmented during ALI. ⋯ We confirm a gravity-related spectral amplitude increase of basic flow-induced breath sounds recorded over lung regions affected by permeability-type pulmonary edema and show that such changes are reversible by alveolar recruitment with PEEP.
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Intensive Care Med Exp · Dec 2014
Uncontrolled sepsis: a systematic review of translational immunology studies in intensive care medicine.
The design of clinical immunology studies in sepsis presents several fundamental challenges to improving the translational understanding of pathologic mechanisms. We undertook a systematic review of bed-to-benchside studies to test the hypothesis that variable clinical design methodologies used to investigate immunologic function in sepsis contribute to apparently conflicting laboratory data, and identify potential alternatives that overcome various obstacles to improve experimental design. ⋯ We found several important and common limitations in the clinical design of translational immunologic studies in human sepsis. Major elective surgery overcame many of these methodological limitations. The failure of adequate clinical design in mechanistic studies may contribute to the lack of translational therapeutic progress in intensive care medicine.