Early alveolar molecular signatures after cardiopulmonary resuscitation: a bronchoalveolar lavage (BALF) proteomic study in swine.

Background: Mechanical chest compressions during cardiopulmonary resuscitation (CPR) can produce pulmonary edema, described as cardiopulmonary resuscitation-associated lung edema (CRALE), which has been largely interpreted as a hydrostatic phenomenon. However, whether early molecular changes associated with epithelial injury, coagulation, and inflammation are also present during resuscitation remains uncertain. We hypothesized that bronchoalveolar lavage fluid proteomics would identify early protein signatures of lung injury after CPR. Methods: Bronchoalveolar lavage fluid (BALF) was collected separately from the right and left caudal lung lobes of nine pigs before cardiac arrest and again after ventricular fibrillation, 8 min of untreated arrest, and up to 45 min of CPR. In animals achieving return of spontaneous circulation, post-CPR BALF was obtained immediately after resuscitation; in the remaining animals, sampling was performed at the end of CPR. Proteins were digested, tandem mass tag 18-plex labeled, and analyzed by high-resolution liquid chromatography-mass spectrometry. Differentially abundant proteins were defined by fold change >1.5 or <0.67 with Results: A total of 1088 proteins were identified in left lung BALF and 1200 in right lung BALF. Comparison of pre- and post-CPR samples identified 74 and 78 differentially abundant proteins in the left and right lungs, respectively, with 28 shared proteins across both lungs. Among the most increased proteins were plasminogen activator inhibitor-1 (SERPINE1/PAI-1), apolipoprotein A1, inter-alpha inhibitor family proteins, vitronectin, histones, and advanced glycation end-product receptor (AGER). Functional enrichment showed over-representation of proteins related to complement and coagulation, platelet degranulation, lipid metabolism, and extracellular matrix signaling. Histology showed mild septal thickening, vascular neutrophilic infiltration, interstitial edema, and patchy fibrin deposition, consistent with early pneumocyte injury and mild inflammation. Western blot confirmed increased post-CPR abundance of PAI-1 and apolipoprotein A1. Conclusions: Early after resuscitation, BALF proteomics identified molecular changes characterized by increased antifibrinolytic and complement-related proteins, together with proteins associated with epithelial and endothelial stress. These findings suggest that pulmonary abnormalities after CPR may involve not only hydrostatic edema but also an early biologic response consistent with lung injury, which may contribute to post-cardiac arrest respiratory dysfunction and progression to acute respiratory distress syndrome.