Ventilator-induced lung injury: historical perspectives and clinical implications.

Mechanical ventilation can produce lung physiological and morphological alterations termed ventilator-induced lung injury (VILI). Early experimental studies demonstrated that the main determinant of VILI is lung end-inspiratory volume. The clinical relevance of these experimental findings received resounding confirmation with the results of the acute respiratory distress syndrome (ARDS) Network study, which showed a 22% reduction in mortality in patients with the acute respiratory distress syndrome through a simple reduction in tidal volume.

Candida albicans impairs macrophage function and facilitates Pseudomonas aeruginosa pneumonia in rat.

Objective: To determine whether Candida albicans airway colonization influences Pseudomonas aeruginosa pneumonia prevalence in rats and by which mechanism.

Design: Prospective, randomized, controlled animal study.

Setting: Research laboratory of a university.

Terbutaline lessens protein fluxes across the alveolo-capillary barrier during high-volume ventilation.

Objective: To evaluate whether a beta2-adrenergic agonist may reduce acute alveolo-capillary barrier alterations during high-volume ventilation.

Design: Experimental study.

Setting: Animal research laboratory.

Pathology underrates colon cancer extranodal and nodal metastases; ex vivo radioimmunodetection helps staging.

Purpose: Colorectal carcinoma is frequently accompanied by small lymph nodes metastases that often escape pathologic examination. We evaluated whether ex vivo radioimmunodetection with the Affinity Enhancement System (AES) could improve detection of mesocolonic metastases.

Experimental Design: A bivalent 111In-labeled hapten was injected (16 patients) 4 days after a bispecific antibody (anticarcinoembryonic antigen, antihapten).

Mechanical ventilation and hemorrhagic shock-resuscitation interact to increase inflammatory cytokine release in rats.

Objective: To determine whether hemorrhagic shock and resuscitation (HSR) and high lung stress during mechanical ventilation interact to augment lung and systemic inflammatory responses and whether their sequence affects these responses.

Design: Prospective, randomized, controlled animal study.

Setting: Research laboratory.

Glucose transport in the lung and its role in liquid movement.

Glucose concentration in the liquid present in the alveolar/airway lumen is the consequence of the balance between removal by lung epithelial cells and entry from the plasma or lung interstitium through the paracellular pathway. Glucose removal is mediated by active, Na(+) -dependent, cotransport and results in transepithelial Na(+) transport and liquid absorption in animals with significant rates of luminal glucose uptake and when luminal glucose concentration is high enough. Cotransport kinetics predicted a low luminal glucose concentration at the steady state, and foetal lung fluid and adult alveolar epithelial lining fluid glucose concentrations were indeed found lower than plasma.

Alveolar edema dispersion and alveolar protein permeability during high volume ventilation: effect of positive end-expiratory pressure.

Objectives: To evaluate whether PEEP affects intrapulmonary alveolar edema liquid movement and alveolar permeability to proteins during high volume ventilation.

Design And Setting: Experimental study in an animal research laboratory.

Subjects: 46 male Wistar rats.

Perflubron dosing affects ventilator-induced lung injury in rats with previous lung injury.

Objectives: Randomized controlled trials of partial liquid ventilation in acute respiratory distress syndrome have been negative. Reasons for this failure may reside in the use of too large doses of perfluorocarbon. The objective was to evaluate whether various doses of perflubron affect ventilation-induced injury in edematous lungs in different ways.

Evaluation of two-way protein fluxes across the alveolo-capillary membrane by scintigraphy in rats: effect of lung inflation.

Pulmonary microvascular and alveolar epithelial permeability were evaluated in vivo by scintigraphic imaging during lung distension. A zone of alveolar flooding was made by instilling a solution containing 99mTc-albumin in a bronchus. Alveolar epithelial permeability was estimated from the rate at which this tracer left the lungs.

Noninvasive evaluation of acute capillary permeability changes during high-volume ventilation in rats with and without hypercapnic acidosis.

Objective: To evaluate whether hypercapnic acidosis attenuates acute alterations of pulmonary capillary permeability due to high lung stretch in rats using a simple, noninvasive, scintigraphic method.

Design: Prospective, randomized, controlled animal study.

Setting: University research laboratory.

Normal pulmonary capillary blood volume in patients with chronic infiltrative lung disease and high pulmonary artery pressure.

Study Objectives: Pulmonary capillary blood volume (Qc), a component of diffusing capacity of the lung for carbon monoxide (Dlco), is increased in postcapillary pulmonary hypertension due to valve disease, but is decreased in primitive and thromboembolic pulmonary hypertension. This study was performed to evaluate which way pulmonary Qc is affected in patients with chronic infiltrative lung disease according to the value of systolic pulmonary artery pressure (SPAP).

Patients And Methods: Twenty-four patients who were nonsmokers and had chronic infiltrative lung disease secondary to connective tissue disease (12 patients), asbestosis (1 patient), sarcoidosis (5 patients), or of unknown origin (6 patients), and 8 control subjects underwent pulmonary function tests and Doppler echocardiography.

Ventilation strategy affects cytokine release after mesenteric ischemia-reperfusion in rats.

Objective: To evaluate the impact of different ventilation modalities on lung and plasma concentrations of cytokines in a model of secondary lung inflammation, mesenteric ischemia-reperfusion, in rats.

Design: Prospective, randomized, controlled animal study.

Setting: Research laboratory of a university.

Imaging apoptosis with (99m)Tc-annexin-V in experimental subacute myocarditis.

Unlabelled: 99mTc-Annexin-V (ANX), which allows in vivo detection of apoptotic cells, is potentially a promising noninvasive tool to diagnose myocarditis. To test this assumption, we compared the myocardial uptake of ANX (imaging and quantitative autoradiography) in experimental subacute myocarditis (Wistar Bonn/Kobori rats [WBN/Kob]) and in normal Wistar rats. WBN/Kob is an inbred strain of Wistar rat in which myocardial injury mimicking subacute catecholamine-induced myocarditis spontaneously develops (course duration, 18 mo).

Infectious and inflammatory dissemination are affected by ventilation strategy in rats with unilateral pneumonia.

Objective: To evaluate the effect of V(T) reduction and alveolar recruitment on systemic and contralateral dissemination of bacteria and inflammation during right-side pneumonia.

Design: Interventional animal study. SETTING.

Dose-response effect of perfluorocarbon administration on lung microvascular permeability in rats.

The effect of various perflubron doses on overdistension lung injury was evaluated. Rats were given perflubron at 0 ml/kg (control) to 20 ml/kg and ventilated with a VT of 33 ml/kg without or with 5 cm H2O of positive end-expiratory pressure (PEEP). High (20 ml/kg), but not lower, perflubron doses aggravated lung capillary leak in the absence of PEEP.

Ventilator-induced lung injury.

During mechanical ventilation, high end-inspiratory lung volume (whether it be because of large tidal volume (VT) and/or high levels of positive end-expiratory pressure) results in a permeability type pulmonary oedema, called ventilator-induced lung injury (VILI). Previous injury sensitises lung to mechanical ventilation. This experimental concept has recently received a resounding clinical illustration after a 22% reduction of mortality was observed in acute respiratory distress syndrome patients whose VT had been reduced.

Neonatal exposure to 65% oxygen durably impairs lung architecture and breathing pattern in adult mice.

Study Objective: To test the hypothesis that exposure to hyperoxia during the postnatal period of rapid alveolar multiplication by septation would cause permanent impairments, even with moderate levels of hyperoxia.

Design: We exposed mouse pups to 65% O(2) (hyperoxic mice) or normoxia (normoxic mice) during their first postnatal month, and we analyzed lung histology, pulmonary mechanics, blood gas, and breathing pattern during normoxia or in response to chemical stimuli in adulthood, when they reached 7 to 8 months of postnatal age.

Results: Hyperoxic mice had fewer and larger alveoli than normoxic mice (number of alveoli per unit surface area of parenchyma, 266 +/- 62/mm(2) vs 578 +/- 77/mm(2), p < 0.

Invited review: Active fluid clearance from the distal air spaces of the lung.

Active ion transport drives iso-osmolar alveolar fluid clearance, a hypothesis originally suggested by in vivo studies in sheep 20 yr ago. Over the last two decades, remarkable progress has been made in establishing a critical role for active sodium transport as a primary mechanism that drives fluid clearance from the distal air spaces of the lung. The rate of fluid transport can be increased in most species, including the human lung, by cAMP stimulation.

Ventilator-induced lung injury.

The clinical relevance of experimental ventilator-induced lung injury has recently received a resounding illustration by the Acute Respiratory Distress Syndrome Network trial that showed a 22% reduction of mortality in patients with acute respiratory disease syndrome when lung mechanical stress was lessened by tidal volume reduction during mechanical ventilation. This clinical confirmation of the concept of ventilator-induced lung injury has also undisputedly substantiated the experimental observation that excessive tidal volume and/or end-inspiratory lung volume is the main determinant of ventilator-induced lung injury. More recently, attention has focused on the roles and implication in the pathogenesis of ventilator-induced lung injury of inflammatory cells and mediators that may be activated and released either in the alveolar space or in the systemic circulation because of the rupture of the alveolar-capillary barrier and on the cellular response to mechanical stress.

Glucose transporter gene expression in freshly isolated and cultured rat pneumocytes.

Alveolar epithelium in situ takes up luminal glucose by cotransport with sodium. Cultured alveolar type II pneumocytes have only sodium-independent glucose uptake. It is unclear which isoforms are responsible for glucose transport in these cells and why sodium-glucose cotransport activity disappears during culture.