A Miniaturized Mouse Extracorporeal Circulation Model to Characterize Early Hematologic and Metabolic Alterations

Xiaoyu Wang¹Xiaohan Cheng¹Xinzhi Pan²Yijie Guo²Ruishi Shen¹Yueyang Zhu¹Adili Abudourousuli³Jiahao Guo⁴Qi Peng⁴Huifang Tang^4*Huashun Cui^1*

• ¹Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
• ²Zhejiang Chinese Medical University, Hangzhou, China
• ³Xinjiang Medical University, Urumqi, China
• ⁴Zhejiang University School of Medicine, Hangzhou, China

Extracorporeal circulation (ECC) is essential in cardiac surgery but triggers severe complications like systemic inflammation, coagulopathy, and end-organ damage. Progress in understanding these events has been hampered by the high cost and complexity of medium-animal models, alongside the technical challenges of operating on mice. To address this, we developed a miniaturized, pre-configured murine ECC system that reliably recapitulates key clinical sequelae of ECC. This novel model, established in C57BL/6 mice, utilizes a low-cost, single-use circuit to maximize reproducibility and minimize contamination. Throughout the procedure, key physiological parameters were monitored and maintained stable. Our system successfully induced hallmark acute-phase responses to ECC, including a systemic inflammatory response (leukocytosis and elevated pro-inflammatory cytokines including IL-1β, IL-6, TNF-α, and IL-18), consumptive coagulopathy (thrombocytopenia), and metabolic stress (elevated lactate levels and electrolyte disturbances). Additionally, early biomarkers associated with organ stress were detected, including elevated cardiac troponin and LDH, increased serum creatinine, elevated AST, and increased pulmonary myeloperoxidase activity. With stable core temperature and pH underscoring the system's controllability, this model provides a reproducible experimental platform for investigating the early molecular mechanisms of ECC-induced systemic responses and for supporting preclinical evaluation of potential therapeutic interventions in cardiovascular research.