Opportunities and short-comings of the axolotl salamander heart as a model system of human single ventricle and excessive trabeculation

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 (ET), or noncompaction. Here, we explore the heart of the axolotl salamander (Ambystoma mexicanum, Shaw 1789) as model system of these diseases. 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. In the axolotl there is a solitary ventricular inlet and outlet, whereas in DILV there are two separate inlets and outlets. Axolotls had a lower resting heart rate compared to DILV (22 vs. 72 beats per minute), lower ejection fraction (47 vs. 58%), and their oxygen consumption at rest was higher than peak oxygen consumption in DILV (30 vs. 17 ml min⁻¹ kg⁻¹). Concerning the ventricular myocardial organization, histology showed trabeculations in ET (n = 5) are much closer to the normal human setting than to the axolotl setting. We conclude that the axolotl heart resembles some aspects of DILV and ET albeit substantial species differences exist.