Objectives: Sepsis-related lung injury is the most common and morbid form of acute lung injury. The objective of this study was to develop an ovine model of septic acute lung injury and characterize its pathophysiology regarding its recruitability and changes in regional aeration and perfusion distributions at injury and during injury evolution.

Design: Experimental animal study.

Setting: University hospital research laboratory.

Subjects: Adult sheep.

Interventions: Twenty-one anesthetized and mechanically ventilated sheep received intravenous Escherichia coli endotoxin infusion until severe hypoxemia was obtained. Inspiratory- and expiratory-gated computed tomography images of the entire lung were acquired in six subjects at baseline, during endotoxin infusion, and at injury. Perfusion images were obtained at apex and base locations at baseline and injury. Computed tomography images were analyzed for total, air, and tissue lung volumes and axial and vertical aeration and perfusion gradients. Lung recruitability was studied in a subgroup of subjects after injury.

Measurements And Main Results: Computed tomography imaging showed a patchy, progressive decrease in air volume as injury evolved, partially replaced by an increase in tissue volume. Perfusion showed a nondependent-to-dependent gradient at baseline that remained relatively unchanged with injury. Perfusion to poorly aerated lung regions was unchanged or increased after injury. Aeration and perfusion distributions at baseline were primarily dorsal or dependent. After injury, the heterogeneity of perfusion and aeration increased and the effect of gravity decreased. Recruitment maneuvers and changes in positive end-expiratory pressure resulted in no improvement in aeration or oxygenation.

Conclusions: The severe hypoxemia, moderate volume loss, and perfusion patterns are consistent with an injury model in which hypoxemia is exacerbated by endotoxin-mediated failure of hypoxic pulmonary vasoconstriction.

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Source
http://dx.doi.org/10.1097/CCM.0b013e3181a02354DOI Listing

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