Establishing a Large Animal Model of VA-ECMO-Induced Pulmonary Low Flow and Its Systemic Effects

Background Extracorporeal membrane oxygenation (ECMO) and artificial lung support are sufficient potential solutions for chronic respiratory failure. However, the long-term consequences of chronic pulmonary low flow for lung and heart, a condition induced by VA-ECMO, remain unknown. This pilot study aims to establish a new long-term 5-day VA-ECMO large animal model and investigate the pathophysiological mechanisms of chronic pulmonary low flow for the first time

Methods & Materials A pilot study used three female domestic pigs (German Landrace, 60-70 kg). The animals were divided into two groups: the VA-ECMO group (n=2), where pulmonary low flow was induced, and the Sham group (n=1), where normal pulmonary blood flow was maintained. The experiment lasted 5 days. Lung tissue samples were collected via video-assisted thoracoscopic surgery (VATS) on day 1 (before and after ECMO placement) and day 3. In contrast, additional organ samples (lung, heart, liver, kidneys, bone marrow, lymph nodes) were obtained directly post-mortem on day 5. Hemodynamic parameters, respiratory function, blood gas levels, and histological/molecular markers of pulmonary remodeling were assessed

Results We successfully implemented the ECMO model, with all pigs maintaining stable vital signs throughout the study. Our preliminary findings are as follows

Pulmonary Remodeling Hematoxylin and eosin (HE) staining demonstrated varying degrees of alveolar wall thickening, epithelial cell hyperplasia, and inflammatory cell infiltration, with these changes becoming more pronounced over time. Remodeling Response Immunohistochemical and molecular analyses indicated an upregulation of inflammatory markers (IL-6, IL-8, IL-10), hypoxia-related factors (HIF-1α), and cardiovascular markers (BNP). The expression levels of vascular remodeling markers (VEGF, PDGF) increased over time, suggesting ongoing vascular and parenchymal changes. Systemic Effects HE staining and imaging revealed swelling, edema, inflammation, and functional changes across the heart, kidney, liver, bone marrow, and lymph nodes, indicating systemic pathology

Conclusion Understanding the physiological consequences of chronic pulmonary low flow is essential for optimizing long-term ECMO therapy and advancing artificial lung development. This study represents a crucial step toward improving lung support strategies for patients with severe respiratory failure, potentially guiding the future design of chronic lung support systems.

Publikationsverlauf

Artikel online veröffentlicht:
25. August 2025