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Research team wants to identify mechanisms in the pulmonary alveoli
Infection with the SARS-CoV2 coronavirus can trigger pneumonia. If the course of covid-19 is severe, it can lead to acute respiratory distress syndrome (ARDS). Affected patients then often have to be ventilated by a machine for weeks. However, mechanical ventilation is a double-edged sword: although it provides the vital oxygen supply, it also damages the lungs, which are already severely damaged by the virus. A research team at Hannover Medical School (MHH) led by Professor Dr. Lars Knudsen at the Institute of Functional and Applied Anatomy and Professor Dr. Ulrich Maus at the Department of Experimental Pneumology is now investigating what happens in the alveoli on a micromechanical level during artificial ventilation of a pre-damaged lung and how this can negatively influence the lung damage. The project in cooperation with partners of the German Centre for Lung Research (DZL) is supported by the German Research Foundation (DFG) with 470,000 euros over three years.
Lung alveoli are interconnected as a fine network
"Covid-19 causes chaos in the lungs of seriously ill patients," says Professor Knudsen. The viruses penetrate the lung parenchyma, i.e. the part of the lung where oxygen is absorbed into the blood. There they prefer to attack the defenders of the alveoli, the alveolar epithelial cells type 2 (AE2). They form the so-called surfactant (surface active agent). This special surfactant reduces the surface tension - like the surfactants in washing-up liquid reduce the surface tension of water. This allows the alveoli to unfold easily and remain open, allowing gas exchange and evenly ventilating the lungs. "SARS-CoV2 damages the alveolar epithelium and the AE2 cells, disrupting the surfacant function and causing the alveoli to collapse," explains the specialist in internal medicine and pneumology. Because the alveoli consist of many folds like a kind of floppy balloon and are connected to each other like a fine network of rubber bands, the shrunken alveoli exert tensile forces on their neighbours and stretch them excessively. This mechanical stress could be further increased during artificial ventilation and permanently damage the walls of the alveoli, which are only a few thousandths of a millimetre thin.
Recreating ventilation situations on the computer
The research team now wants to investigate in the mouse model whether lung damage is actually intensified by artificial ventilation due to the interplay between collapsed and open alveoli, and whether the collapsed alveoli act as germinal centres to ensure that the damage in the alveolar epithelium spreads further. "Unfortunately, we cannot watch the alveoli at work, because our imaging techniques are too imprecise to show the wafer-thin walls of the alveoli," says Professor Knudsen. The studies are therefore based on observations of tissue sections using light and electron microscopy techniques.
In pre-damaged, ventilated lungs, mechanical data such as elasticity and extensibility of the lung parenchyma as well as structural data of the alveoli such as the number of their folds or their volume are to be combined in computer models that can be used to simulate different ventilation situations. Since both the structure of the mouse lung and the mechanisms of respiration show parallels with our lungs, the results can be transferred. "In humans, of course, gravity, age and previous illnesses also play a role," admits the pneumologist. In general, however, general conclusions can be drawn about the conditions under which artificial respiration causes the least damage to the lungs. In addition, the research team wants to test whether the alveoli can be stabilised at an early stage with the help of finely atomised surfactant, and thus prevent additional damage through mechanical ventilation.
Background information: How gas exchange works in the lungs
The alveoli are outpouchings of the airways that form the fine tissue of the lungs. Covered with blood vessels (capillaries), they are the place where gas exchange takes place between the blood and the air. At these points, the vital oxygen from inhaled air enters the blood vessels of the lungs and is transported with the bloodstream to the organs and tissues. At the same time, the blood in the lung vessels releases carbon dioxide back into the alveoli, which is then exhaled.
SERVICE:
For more information, contact Professor Dr Lars Knudsen, knudsen.lars@mh-hannover.de, telephone (0511) 532-2888.
Professor Dr Lars Knudsen with a spout model of a human lung.
Copyright: Karin Kaiser / MHH
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