Novel Acute and Survival Models of Veno-venous and Veno-arterial ECMO in a Mouse as an Essential Research Tool with Clinical Relevancy in the Study of End-Stage Heart and Lung Diseases

Objectives: Extracorporeal membrane oxygenation is an effective method of treatment in end-stage cardiopulmonary conditions. We have previously demonstrated fully functioning cardiopulmonary bypass in a mouse model. Availability of knock-in/out mice suffering from terminal heart and lung conditions would allow answering many questions on molecular mechanisms ongoing under ECMO support. We have developed both acute and survival models of V/V and V/A ECMO in mice. Effect of the ECMO was evaluated at 2, 4, 6, and 24 hours after “weaning.”

Methods: ECMO circuit had a total priming volume of 0.5 mL. For acute model, 6 C57Bl/6 mice in each group were subjected to 2, 4, and 6 hours of V/V ECMO followed by organ sampling. BGA, invasive blood pressure, ECG, and rectal temperature were monitored. Sham groups underwent similar surgery without ECMO. Surviving model included performance of 2 hours of V/V and V/A ECMO in eight animals per group followed by weaning and observation for 24 hours. Read-out parameters included clinical chemistry, blood gas analysis and histology of heart, lungs, kidney, liver, and intestine.

Results: Clinical chemistry showed relevancy with clinical data with significant increase in LDH, lactate, GOT, urea and creatinine levels correlating with the duration of the ECMO. Histological assessment showed moderate tubular damage in kidney, transient loss of glycogen in liver and extravasation of vesicles in the intestine especially after 6 hours of the ECMO treatment. Lung histology demonstrated peripheral neutrophilia with signs of coagulopathy in prolonged ECMO. Histology obtained in 2 hours after ECMO treatment was not prominent. Heart morphology did not show alterations in all groups. In surviving model no blood transfusion was done and over 85% of animals subjected to 2 hours of V/V and V/A ECMO fully recovered after weaning and reached 24 hours in a good condition. In these animals no significant morphological changes in internal organs were observed.

Conclusions: We have established both acute and chronical surviving models of V/V and V/A ECMO in a mouse and obtained results similar to clinical observations. Availability of knock-in/out mice with cardiopulmonary disorders could help to reveal diverse unknown pathways in end-stage conditions requiring ECMO treatment. Such models of extracorporeal support could be of indispensable value in diverse studies focusing on inflammatory response and perfusion.

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