Cauterization of the root of the left coronary artery as a straightforward, large and reproducible ischemic injury model in neonatal mice

Abstract

The adult mammalian heart is known to have very limited regenerative capacity, explaining at least in part the frequency of cardiovascular diseases and their impact as the leading cause of death worldwide. By contrast, the neonatal heart has the ability to regenerate upon injury, and the molecular mechanisms underlying this regenerative capacity are intensely investigated to provide novel cues for the repair of the adult heart. However, the existing rodent neonatal injury models—apex resection, left anterior descending artery ligation and cryoinjury—have limitations, such as being technically demanding, yielding a nonphysiological injury type and/or lack of reproducibility. Here we have therefore established a novel ischemic heart injury method in neonatal mice via cauterization of the root of the left coronary artery. This surgical procedure is technically straightforward, requires less than 10 min for completion and yields reproducible, large ischemic lesions (40% of the left ventricle) with low mortality rates (10% of animals). The injury also induces secondary pulmonary hypertension shortly after surgery, allowing to study the response of the right ventricle. Moreover, neonatal mice at postnatal days 1 and 3 display strongly opposing outcomes after the surgery, because of the lack of cardiac regeneration at the later stage. Thus, this new neonatal heart injury model is of great use for mechanistic studies exploring the regeneration of the left ventricle and the adaptation of the right ventricle upon myocardial infarction.