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An altered glucose concentration increases plasma membrane injury in alveolar cells
Critical Care volume 10, Article number: P245 (2006)
Lung injury has been associated with such insults as inflammation, infection, transfusion of blood products and mechanical ventilation with high tidal volumes (VALI). In the critically ill, intensive control of hyperglycemia with insulin results in decreased mortality and length of ICU stay. Whether or not abnormal glucose concentration contributes to VALI is unknown. The purpose of this study was to evaluate the role of an altered glucose environment in lung cell injury.
In in-vitro experiments, rat type II alveolar cells were cultured on a flexible membrane in the presence of low (100 mg/dl), normal (400–500 mg/dl) and high (700 mg/dl) glucose concentrations (standard growth media = 400 mg/dl). Cells were stretched by deforming the membrane cyclically eight times per minute for 2 min. Cell stretch was performed in the presence of fluorescein isothiocyanate-dextran, a marker of plasma membrane injury and reseal. Following cell stretch, cells were labeled with propidium iodide (PI), a marker of cell death. Cell injury was expressed as the number of injured and dead cells over the total number of cells.
In in-vivo experiments, isolated rat lungs were mechanically ventilated with injurious tidal volumes (initial tidal volume 40 ml/kg, adjusted to initial peak airway pressure = 25 cmH2O) for 25 min while perfused with Kreb's solution of normal (120 mg/dl) or high (500 mg/dl) glucose concentration. PI was added to the perfusate during injurious ventilation. The number of labeled subpleural cells was measured and reported as an injury index (labeled nuclei/number of alveoli in each view field).
At a glucose concentration lower than that found in standard type II cell growth media, there was increased injury following cell stretch (27.6% vs 18.9%, P = 0.01). At higher glucose concentrations cells no longer were adherent to the deformable membrane, which is a strong marker of nonviability. In rat lungs perfused with high-glucose Kreb's solution during injurious ventilation there was significantly greater injury than in lungs perfused with normal glucose Kreb's solution (28.0% vs 10.1%, P < 0.01).
States of altered glucose homeostasis result in increased cell injury in both cell stretch and isolated lung models of injurious ventilation. These findings highlight the importance of tight glucose control in the lung cell environment to ensure the integrity of the alveolar capillary membrane. They also suggest that cell injury and resulting alveolar-capillary leakiness may explain the worse clinical outcome and increased incidence of bacteremia seen in critically ill patients with hyperglycemia. Further study is warranted to define the mechanism through which altered glucose homeostasis contributes to lung cell injury and VALI.
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Ensminger, S., Vlahakis, N. An altered glucose concentration increases plasma membrane injury in alveolar cells. Crit Care 10, P245 (2006). https://doi.org/10.1186/cc4592
- Glucose Concentration
- Tidal Volume
- High Tidal Volume
- Tight Glucose Control
- Altered Glucose