A Murine Model of Veno-Arterial Extracorporeal Membrane Oxygenation

The mechanisms driving the pathologic state created by extracorporeal membrane oxygenation (ECMO) remain poorly defined. We developed the first complete blood-primed murine model of veno-arterial ECMO capable of maintaining oxygenation and perfusion, allowing molecular studies that are unavailable in larger animal models. Fifteen C57BL/6 mice underwent ECMO by cannulating the left common carotid artery and the right external jugular vein. The mean arterial pressure was measured through cannulation of the femoral artery. The blood-primed circuit functioned well. Hemodynamic parameters remained stable and blood gas analyses showed adequate oxygenation of the animals during ECMO over a 1-hour timeframe. A significant increase in plasma-free hemoglobin was observed following ECMO, likely secondary to hemolysis within the miniaturized circuit components. Paralleling clinical data, ECMO resulted in a significant increase in plasma levels of multiple proinflammatory cytokines as well as evidence of early signs of kidney and liver dysfunction. These results demonstrate that this novel, miniature blood-primed ECMO circuit represents a functional murine model of ECMO that will provide unique opportunities for further studies to expand our knowledge of ECMO-related pathologies using the wealth of available genetic, pharmacological, and biochemical murine reagents not available for other species.

[1]  J. Maessen,et al.  Understanding the “extracorporeal membrane oxygenation gap” in veno‐arterial configuration for adult patients: Timing and causes of death , 2021, Artificial organs.

[2]  M. Shankar-Hari,et al.  Current Understanding of Leukocyte Phenotypic and Functional Modulation During Extracorporeal Membrane Oxygenation: A Narrative Review , 2021, Frontiers in Immunology.

[3]  Mahesh S. Sharma,et al.  Impact of Circuit Size on Coagulation and Hemolysis Complications in Pediatric Extracorporeal Membrane Oxygenation , 2020, ASAIO journal.

[4]  J. Storm-Mathisen,et al.  Blood lactate dynamics in awake and anaesthetized mice after intraperitoneal and subcutaneous injections of lactate—sex matters , 2020, PeerJ.

[5]  F. Gueler,et al.  Four hours of veno-venous extracorporeal membrane oxygenation using bi-caval cannulation affects kidney function and induces moderate lung damage in a mouse model , 2019, Intensive Care Medicine Experimental.

[6]  H. Buerkle,et al.  Phosphodiesterase-4 inhibition reduces ECLS-induced vascular permeability and improves microcirculation in a rodent model of extracorporeal resuscitation. , 2019, American journal of physiology. Heart and circulatory physiology.

[7]  A. Haverich,et al.  Veno-Venous Extracorporeal Membrane Oxygenation in a Mouse. , 2018, Journal of visualized experiments : JoVE.

[8]  F. Gueler,et al.  Blood cytokine expression correlates with early multi-organ damage in a mouse model of moderate hypothermia with circulatory arrest using cardiopulmonary bypass , 2018, PloS one.

[9]  M. Riccabona,et al.  Neonatal Extracorporeal Membrane Oxygenation Due to Respiratory Failure: A Single Center Experience Over 28 Years , 2018, Front. Pediatr..

[10]  D. Sidebotham,et al.  Hyperlactatemia and Cardiac Surgery. , 2017, The journal of extra-corporeal technology.

[11]  D. Gommers,et al.  Microcirculatory assessment of patients under VA-ECMO , 2016, Critical Care.

[12]  M. van Meurs,et al.  Impaired microcirculatory perfusion in a rat model of cardiopulmonary bypass: the role of hemodilution. , 2016, American journal of physiology. Heart and circulatory physiology.

[13]  Ke Lin,et al.  A Novel Minimal Invasive Mouse Model of Extracorporeal Circulation , 2015, Mediators of inflammation.

[14]  Y. Son,et al.  Effect of Sodium Bicarbonate Administration on Mortality in Patients with Lactic Acidosis: A Retrospective Analysis , 2013, PloS one.

[15]  N. Iversen,et al.  The normal acid–base status of mice , 2012, Respiratory Physiology & Neurobiology.

[16]  Jeffrey D Fortman,et al.  Effects of weekly blood collection in C57BL/6 mice. , 2011, Journal of the American Association for Laboratory Animal Science : JAALAS.

[17]  R. Schelonka,et al.  Plasma Concentrations of Inflammatory Cytokines Rise Rapidly during ECMO-related SIRS due to the Release of Pre-formed Stores in the Intestine , 2009, Laboratory Investigation.

[18]  W. S. Haworth The development of the modern oxygenator. , 2003, The Annals of thoracic surgery.

[19]  J. Rosenbaum,et al.  Reduced leukocyte migration, but normal rolling and arrest, in interleukin-8 receptor homologue knockout mice. , 2000, Investigative ophthalmology & visual science.

[20]  K M Taylor,et al.  A literature review of cardiopulmonary bypass models for rats , 1999, Perfusion.

[21]  F. Gueler,et al.  Novel mouse model of cardiopulmonary bypass , 2018, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.