The effect of nitric oxide (II) on the extracellular matrix of the lungs during cardiopulmonary bypass: an experimental study

Cardiac surgeries with cardiopulmonary bypass (CBP) lead to significant changes in the morphofunctional state of the lungs, accompanied by the formation of post-perfusion pulmonary syndrome. Reperfusion significantly increases lung damage due to the influx of oxygen and calcium ions, as well as leukocytes and blood clotting system components activated by contact with the apparatus circuit material. Cells of the inflammatory infiltrate damage matrix proteins by releasing proteolytic enzymes that damage the structure of collagen and elastin and lead to the formation of their modified forms with altered spatial organization and mechanical properties. Nitric oxide (II) (NO) has the potential to affect the key pathogenic mechanisms of ischemic-reperfusion damage. Under cardiopulmonary bypass, there is a deficiency of endogenous nitric oxide, so perioperative delivery of exogenous NO is likely to compensate for this deficiency.

Aim: To characterize the changes occurring in the intercellular matrix of the lungs under the conditions of simulated surgeries with cardiopulmonary bypass and the effect of perioperative delivery of nitric oxide on their severity.

Material and Methods. The study was conducted on 6 male domestic sheep. The animals of the “CBP” group (n = 3) underwent CBP and mechanical ventilation (MV) according to the standard procedure. In the “CBP + NO” group (n = 3), sheep additionally received nitric oxide (II) at a dose of 80 ppm through modified circuits of ventilators and cardiopulmonary bypass throughout the experiment. The duration of cardiopulmonary bypass was 90 minutes. The content of matrix metalloproteinases-2 and -9 in the lungs was assessed by immunohistochemistry. Collagen fibers were detected by Van – Gieson staining and an immunohistochemical reaction to type I collagen.

Results. In the lungs of sheep treated with nitric oxide on the background of cardiopulmonary bypass, a decrease in the intensity of immune staining for MMP-2 (p < 0.001) and MMP-9 (p < 0.001), higher specific volume (p < 0.001) and qualitative characteristics of collagen fibers were noted.

Conclusion. The use of nitric oxide in experimental modeling of cardiac surgery helps to limit the damaging effect of cardiopulmonary bypass on the intercellular matrix of the lungs.

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