The axolotl heart is capable of full anatomical and functional regeneration following cryoinjury induced ventricular infarction

Myocardial infarction (MI), the result of coronary artery occlusion and subsequent ischemia, is a leading cause of death globally. Though rapid medical intervention can reduce the risk of immediate demise, the resulting necrotic tissue after MI initiates an inflammatory response that activates reparative mechanisms. Local fibroblasts are recruited and activated, and ultimately the damaged myocardium is replaced with collagen-rich scar tissue.

This provides a rapid solution to cardiac injury by stabilization of the damaged area. However, the scar tissue is not contractile resulting in a weakened cardiac output, increased susceptibility to aneurysm, and the induction of compensatory pathology that can eventually result in heart failure. Medical therapies that can facilitate survival and/or replacement of myocardium after ischemic injury in the human heart are urgently needed and would have tremendous social and economic impact.

Animal models traditionally used in biomedical research such as mouse, rat, rabbit, pig, etc. all respond relatively similar to MI as human patients. Even though these models animals are essential for the final steps of preclinical development of therapies before entering clinical trials, these traditional models should not be promoted narrow-mindedly to discover basic mechanism with implications in medicine. In the quest of developing cardiac regenerative therapies, vertebrate model species outside the mammalian class with intrinsic regenerative capabilities can be applied with advantage.

The two best established model animals in cardiac regenerative research are the zebrafish and the salamander which in addition to perform complete regeneration after ventricular damage are able to regenerate as diverse structures as intestines, liver, skeletal muscle, central and peripheral nervous system, lens, retina, jaw, and even whole appendages such as limbs (fins) and tail Superficially, these animals may seem too distantly related to humans to be of any interest for medical research. However, on the contrary, the building plan for the heart is strikingly conserved within all vertebrates, and zebrafish and salamander cardiac regeneration closely resembles cardiac development, and in the case of injury, cardiac regeneration, in embryonic mammals.

Therefore, understanding the basic mechanisms that allow zebrafish and salamanders to regenerate, and which are lost in humans after the embryonic state, can have very important implications in the development of regenerative therapies in human patients.