A Rat Model of Clinically Relevant Extracorporeal Circulation Develops Early Organ Dysfunctions

Area of Science:

• Cardiovascular Surgery
• Translational Medicine
• Preclinical Research

Background:

• Extracorporeal circulation (ECC) can cause coagulopathy, inflammation, and organ injury in patients.
• Existing large animal models are costly, necessitating the development of more affordable alternatives.
• Rodent models require validation to ensure clinical relevance for ECC-related research.

Purpose of the Study:

• To develop a novel rat model for veno-arterial extracorporeal circulation (ECC).
• To establish the clinical relevance of this rat ECC model by comparing its physiological and molecular responses to human patients undergoing cardiac surgery.
• To assess the utility of this model for preclinical studies of ECC-associated pathophysiology.

Main Methods:

• Rats underwent 1 hour of veno-arterial ECC or a sham procedure under mechanical ventilation.
• Hemodynamics, behavior, and blood biomarkers were measured 5 hours post-surgery.
• Biomarker patterns and transcriptomic data were compared between rats and 41 human patients undergoing on-pump cardiac surgery.

Main Results:

• Rats exhibited hypotension, hyperlactatemia, and behavioral changes post-ECC.
• Similar patterns of key biomarkers (LDH, CK, ASAT, ALAT, Troponin T) were observed in both rats and human patients.
• Transcriptomic analysis revealed conserved biological processes in response to ECC in both species, indicating shared pathophysiological pathways.

Conclusions:

• The developed rat ECC model replicates key clinical features and pathophysiological responses seen in human ECC procedures.
• This model demonstrates early organ injury, reflecting a severe phenotype relevant to clinical ECC complications.
• The rat ECC model offers a relevant, cost-effective preclinical tool for investigating human ECC-associated pathophysiology and potential therapeutic interventions.