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Abstract

Atelectasis and mucus plugging are common complications following pediatric cardiac surgery with cardiopulmonary bypass (CPB). Mucins increase in airway lavage after pediatric CPB; however, tissue expression and regional variation remain to be evaluated in a translational model. The objective of this study was to analyze mucins in the lungs of infant pigs undergoing CPB with deep hypothermic circulatory arrest (DHCA). Piglets underwent CPB with DHCA followed by survival for 4 h (n = 5). Anesthesia controls (n = 7) were mechanically ventilated for 7 h without CPB. Gene expression of Muc4, Muc5AC, and Muc5B in the right apex (RA) and right lower lobe (RLL) was analyzed using RT-PCR, and localization and production were evaluated by immunohistochemistry. CPB/DHCA animals had significantly increased Muc4 (26.7 ± 30.6 vs 1.2 ± 1.2; p = 0.017), Muc5AC (7.8 ± 8.6 vs 1.1 ± 1.0; p = 0.0025), and Muc5B (8.1 ± 8.9 vs 1.5 ± 1.4; p = 0.017) mRNA levels and higher number of Muc5B positive cells in submucosal glands and bronchiole surface of the RLL compared to controls, with similar trends in the RA. Muc5AC localized mainly to bronchiole goblet cells, and its production qualitatively increased in the lungs of CPB/DHCA animals. Tissue mucin expression and production increase in the lungs of piglets exposed to CPB/DHCA, particularly in the lower lobes. Thus, the risk of mucus plugging in the acute period may be somewhat higher in the lower lobes, which are already affected by atelectasis and inflammation. Our model may serve as a valuable platform for future studies evaluating the mechanism and therapy of mucin production and airway obstruction following pediatric cardiac surgery. New and noteworthy: We provide insight to mucin expression and its regional variations in the lungs of piglets undergoing CPB with DHCA. Increased tissue mucins in the lower lobes suggest a potential mechanism for atelectasis and mucus plugging in the postoperative period. They also represent a novel therapeutic target, as Muc5AC therapeutic small interfering RNAs are currently being tested in phase 1/2a clinical trial.

Keywords

Mechanical ventilation pediatric cardiac surgery Muc4 Muc5AC Muc5B

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Changes in mucin expression in the lungs of infant piglets following cardiopulmonary bypass with deep hypothermic circulatory arrest

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