Local strain distribution in real three-dimensional alveolar geometries.

Mechanical ventilation is not only a life saving treatment but can also cause negative side effects. One of the main complications is inflammation caused by overstretching of the alveolar tissue. Previously, studies investigated either global strains or looked into which states lead to inflammatory reactions in cell cultures. However, the connection between the global deformation, of a tissue strip or the whole organ, and the strains reaching the single cells lining the alveolar walls is unknown and respective studies are still missing. The main reason for this is most likely the complex, sponge-like alveolar geometry, whose three-dimensional details have been unknown until recently. Utilizing synchrotron-based X-ray tomographic microscopy, we were able to generate real and detailed three-dimensional alveolar geometries on which we have performed finite-element simulations. This allowed us to determine, for the first time, a three-dimensional strain state within the alveolar wall. Briefly, precision-cut lung slices, prepared from isolated rat lungs, were scanned and segmented to provide a three-dimensional geometry. This was then discretized using newly developed tetrahedral elements. The main conclusions of this study are that the local strain in the alveolar wall can reach a multiple of the value of the global strain, for our simulations up to four times as high and that thin structures obviously cause hotspots that are especially at risk of overstretching.

Material model of lung parenchyma based on living precision-cut lung slice testing.

We describe a novel constitutive model of lung parenchyma, which can be used for continuum mechanics based predictive simulations. To develop this model, we experimentally determined the nonlinear material behavior of rat lung parenchyma. This was achieved via uni-axial tension tests on living precision-cut rat lung slices. The resulting force-displacement curves were then used as inputs for an inverse analysis. The Levenberg-Marquardt algorithm was utilized to optimize the material parameters of combinations and recombinations of established strain-energy density functions (SEFs). Comparing the best-fits of the tested SEFs we found Wpar = 4.1 kPa(I1-3)2 + 20.7 kPa(I1 - 3)3 + 4.1 kPa(-2 ln J + J2 - 1) to be the optimal constitutive model. This SEF consists of three summands: the first can be interpreted as the contribution of the elastin fibers and the ground substance, the second as the contribution of the collagen fibers while the third controls the volumetric change. The presented approach will help to model the behavior of the pulmonary parenchyma and to quantify the strains and stresses during ventilation.

The impact of smoking on outcomes among patients undergoing hematopoietic SCT for the treatment of acute leukemia.

A paucity of research exists examining the potential impact of tobacco use on cancer treatment outcomes, especially among patients treated with hematopoietic SCT (HSCT). A retrospective cohort study design was used to examine the impact of smoking on duration of hospitalization and overall survival among 148 consecutive patients undergoing HSCT for treatment of acute leukemia from 1999 to 2005. Of the 148 patients, 15% reported current smoking, 30% former smoking, and 55% never used tobacco. Patients were followed for a median 3.5 years (interquartile range=2.1-5.5). Compared to no history of smoking, current smoking was associated with worse pre-HSCT pulmonary function tests (P<0.02 in each case), more days hospitalization (46.2 days versus 25.7 days, P=0.025), and poorer overall survival (hazard ratio (HR)=1.88; 95% CI 1.09-3.25). Results were similar after multivariate adjustment, although the association with overall survival attenuated slightly (HR=1.75; 95% CI 1.00-3.06). Current smoking appears to adversely affect the number of days hospitalized post HSCT and overall survival. Translational research focused on interventions to promote tobacco cessation may lead to improved HSCT outcomes.

Role of the carotid bodies in the respiratory compensation for the metabolic acidosis of exercise in humans.

1. In response to an acute exercise-induced metabolic acidosis, the fall of arterial pH is constrained by the magnitude of the compensatory hyperventilation. To determine the role of the carotid bodies in this regulatory process, subjects performed prolonged (24 min) square-wave cycle ergometry from a background of unloaded cycling at inspired oxygen fractions (FI,O2) of 0.12 O2 (high carotid body gain), 0.21 O2 (normal carotid body gain) and 0.80 O2 (low carotid body gain). The work rates were selected to provide the same exercise intensity, despite the different inspirates; i.e. resulting in a constant increase in arterial blood [lactate] (delta [L-] approximately 4 mequiv l-1. 2. Ventilatory and pulmonary gas exchange variables were computed breath-by-breath and arterial blood was sampled at intervals throughout the tests and analysed subsequently for [lactate], [pyruvate], arterial partial pressures of oxygen and carbon dioxide (PO2, PCO2), pH, [bicarbonate] and [potassium]. 3. Hypoxia markedly reduced, and hyperoxia magnified, the transient decrease in arterial pH following exercise onset. However, there was a slow acid-base compensatory component, even when carotid chemosensitivity was suppressed by hyperoxia. We therefore conclude that, in humans, carotid body chemosensitivity plays a dominant role in constraining variations of arterial pH in response to the acute metabolic acidosis of heavy exercise, but that secondary-presumably central chemosensory-mechanisms subserve a slower compensatory role.