# A miniaturized mouse extracorporeal circulation model to characterize early hematologic and metabolic alterations

**Authors:** Xiaoyu Wang, Xiaohan Cheng, Xinzhi Pan, Yijie Guo, Ruishi Shen, Yueyang Zhu, Adili Abudourousuli, Jiahao Guo, Qi Peng, Huifang Tang, Huashun Cui

PMC · DOI: 10.3389/fphys.2026.1740282 · Frontiers in Physiology · 2026-02-13

## TL;DR

Researchers created a miniaturized mouse model to study the early effects of extracorporeal circulation, mimicking clinical complications like inflammation and metabolic stress.

## Contribution

A low-cost, reproducible murine ECC system that reliably induces clinical sequelae for studying systemic responses.

## Key findings

- The model induced systemic inflammation with elevated IL-1β, IL-6, TNF-α, and IL-18.
- Metabolic stress markers like lactate and electrolyte disturbances were observed.
- Early biomarkers of organ stress, including cardiac troponin and LDH, were detected.

## Abstract

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.

## Linked entities

- **Proteins:** IL1B (interleukin 1 beta), IL6 (interleukin 6), TNF (tumor necrosis factor), IL18 (interleukin 18), Ldh (Lactate dehydrogenase)

## Full-text entities

- **Genes:** Thpo (thrombopoietin) [NCBI Gene 21832] {aka Mgdf, Ml, Mpllg, Tpo}, Il18 (interleukin 18) [NCBI Gene 16173] {aka Igif, Il-18}, Cygb (cytoglobin) [NCBI Gene 114886] {aka 3110001K20Rik, HGb, Staap}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Cd40lg (CD40 ligand) [NCBI Gene 21947] {aka CD154, CD40-L, Cd40l, HIGM1, IGM, IMD3}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Atcay (ataxia, cerebellar, Cayman type) [NCBI Gene 16467] {aka 3322401A10Rik, BNIP-H, CLAC, hes, ji}, Slc17a5 (solute carrier family 17 (anion/sugar transporter), member 5) [NCBI Gene 235504] {aka 4631416G20Rik, 4732491M05, AST, ISSD, NSD, SD}, Tpo (thyroid peroxidase) [NCBI Gene 22018], Mpo (myeloperoxidase) [NCBI Gene 17523] {aka mKIAA4033}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Pf4 (platelet factor 4) [NCBI Gene 56744] {aka Cxcl4, Scyb4}
- **Diseases:** bleeding (MESH:D006470), arrhythmia (MESH:D001145), Organ injury (MESH:D009102), acute kidney injury (MESH:D058186), hypotension (MESH:D007022), platelet dysregulation (MESH:D021081), cardiac electrical instability (MESH:D004556), hemolysis (MESH:D006461), Cat (MESH:D002371), inflammation (MESH:D007249), trauma (MESH:D014947), circulatory failure (MESH:D012769), Hyperkalemia (MESH:D006947), mitochondrial dysfunction (MESH:D028361), SIRS (MESH:D018746), multiorgan failure (MESH:D051437), lymphopenia (MESH:D008231), blood loss (MESH:D016063), pulmonary injury (MESH:D055370), impairment of renal perfusion (MESH:D007674), organ damage (MESH:D000092124), postoperative (MESH:D019106), hepatic injury (MESH:D056486), Cardiac involvement (MESH:D006331), acidemia (MESH:C537358), inflammatory storm (MESH:C566109), tissue injury (MESH:D017695), consumptive coagulopathy (MESH:D004211), anemia (MESH:D000740), hypocalcemia (MESH:D006996), thrombus (MESH:D013927), reperfusion injury (MESH:D015427), Death (MESH:D003643), complement (MESH:D007153), monocytosis (MESH:C538328), hematologic (MESH:D006402), neutrophilia (MESH:C563010), neurocognitive dysfunction (MESH:D019965), infection (MESH:D007239), coagulopathy (MESH:D001778), end-organ damage (MESH:C564816), thrombocytopenia (MESH:D013921), myocardial ischemia (MESH:D017202), ECC (MESH:D009360), Metabolic acidosis (MESH:D000138), leukocytosis (MESH:D007964)
- **Chemicals:** cCl (MESH:D002433), chloride (MESH:D002712), oxygen (MESH:D010100), lactate (MESH:D019344), carbon dioxide (MESH:D002245), polypropylene (MESH:D011126), sevoflurane (MESH:D000077149), heparin (MESH:D006493), Cr (MESH:D003404), calcium (MESH:D002118), reactive oxygen species (MESH:D017382), EM30867S (-), K+ (MESH:D011188), sodium (MESH:D012964), PVC (MESH:D011143), HCO3 - (MESH:D001639)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Felis catus (cat, species) [taxon 9685]
- **Cell lines:** C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12945805/full.md

## References

42 references — full list in the complete paper: https://tomesphere.com/paper/PMC12945805/full.md

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Source: https://tomesphere.com/paper/PMC12945805