Streaming of disparate blood flows in single ventricles as a possible mechanism for survival in amphibians and human. Opportunities and short-comings of the axolotl salamander heart as model.

Background: Few experimental model systems are available for the rare congenital heart diseases of double inlet left ventricle (DILV), a subgroup of univentricular hearts, and excessive trabeculation, or noncompaction (ET). The long-term survival of certain functionally univentricular heart patients without Fontan circulation is related to favorable intraventricular streaming of blood streams with disparate oxygen saturation. Here, we explore the heart of the axolotl salamander (Ambystoma mexicanum, Shaw 1789) as a model system of these diseases. Aim: To characterize heart function and structure of the axolotl hearts in comparison to human cases of DILV and ET. Methods and Results: Using micro-echocardiography, we assessed the form and function of the heart of the axolotl, an amphibian, and compared this to human DILV (n=3). The main finding was that both in the axolotl and DILV, blood flows of disparate oxygen saturation can stay separated in a single ventricle. Differences were also found: the axolotl has a common ventricular inlet and outlet, whereas in DILV, there are two separate inlets and outlets. The axolotls had a lower resting heart rate compared to DILV (22 versus 72 beats per minute), lower ejection fraction (47 versus 58%), and their oxygen consumption at rest was higher than peak oxygen consumption in DILV (30 versus 17 ml min-1 kg-1). Furthermore, ventricular myocardial organization of axolotl and ET (n=5) was compared with histology showing that trabeculations in ET are closer to the normal human setting than to the axolotl setting. Conclusions: The axolotl heart resembles and models some aspects of DILV and ET.