Cardiopulmonary bypass in a mouse: novel small animal model

Introduction: In contrast to rat, mice offer the possibility of using genetically modified animals suffering from cardiomyopathy, coronary diseases, aortic aneurism, cystic fibrosis, pulmonary hypertony, moreover, a much brighter spectrum of mouse antibodies and reagents are available on the market. We describe a novel small animal model of cardiopulmonary bypass in mouse suited to answer many pathophysiological questions in an accelerated and inexpensive fashion.

Methods: Experimental design involved establishment of low flow peristaltic pump, micro-cannulation tubing and micro-oxygenator. Self-rebuilt peristaltic pump provided flow of 2-7 ml/min, polyethylene tubing were from 0,36 to 0,5 mm. Micro-oxygenator had a 300 microliter chamber and incapacitating 6 hollow polypropylene fibers able to conduct oxygen at 0,5 L/min. Reservoir consisted of 2 ml chamber with 2 inflow and 1 outflow micro connections. After the intubation, arterial inflow was connected via left common carotid artery and venous outflow was drained through right jugular vein. For visual monitoring median sternotomy was used. Priming consisted of 0,5 ml of HES and 1 ml of Ringer solution. Cardioplegia was done using St. Thomas solution given through carotid artery after clamping of descending aorta and pouring cold saline drops on a heart. At the end of experiment, all animals were sacrificed under isoflurane anesthesia.

Results: Novel model of CPB provided sufficient circulation and oxygenation in 5 mice weighing 25 to 30 g. In all acute experiments inotrope medications were avoided. Mean arterial pressure was maintained at 50 to 70 mmHg. Maximal HLM time used was 1 h, cardioplegia time used was 10 min and artificial apnoe was limited to 30 min. CPB had shown fully stable hemodynamic parameters proven on invasive blood pressure monitoring. BGA performed in every 10 min of experiment demonstrated sufficient arterial and venous gas parameters comparable to the rat model. In 2 min after reperfusion heart-beat recovery was documented.

Conclusion: We have developed a new mouse model of CPB that provides stable and reproducible haemodynamic and respiratory parameters correlating to data reported for rat CPB‘s. The next steps involve establishing of chronical models of knock out/in mouse CPB for clinically relevant surgical interventions and studies. Such models of clinical relevant diseases carry an indispensable value and offer a huge number of benefits for animal research.