Suture-to-scan: ultrasonography-guided induction of heart injury

Heart and circulatory diseases affect 1 in 13 people globally. This disease class encompasses both inherited and acquired conditions, such as coronary artery disease. Occlusion of the coronary vasculature can lead to acute myocardial infarction, which results from thrombus formation and the accompanying cessation of blood flow to the distal myocardium. This lack of blood flow leads to myocardial ischaemia and the subsequent maladaptive and pathological remodelling of the left ventricle that can ultimately progress to heart failure. Given the paucity of clinically tested therapies that can induce cardiac regeneration after myocardial infarction, experimental models are essential to improve our mechanistic understanding of this disease process. To date, a multitude of surgical approaches have been implemented to induce an ischaemic cardiac event and model the pathophysiology of myocardial infarction in rodents. Since 1995, permanent ligation of the left anterior descending coronary artery has been a standard practice for inducing myocardial infarction in vivo in mice. However, this invasive method involves mechanical ventilation and an open thoracotomy and requires technically demanding surgical skills. Furthermore, differences in operator experience level can result in variation in infarct induction, and perioperative mortality of >50% is not uncommon with this surgery.

We have used this technique in a lymphatic endothelial cell-specific multispectral lineage-tracing mouse model to assess the temporal lymphangiogenic response in the acute phase of myocardial infarction. In response to tamoxifen administration, these mice stochastically express one of four fluorescent proteins (red fluorescent protein, membrane-targeted cyan fluorescent protein, nuclear-targeted green fluorescent protein or yellow fluorescent protein) in prospero homeobox protein 1-expressing lymphatic endothelial cells. Clonal proliferation by lymphatic endothelial cells can be quantified in this model in a spatial and temporal manner by comparing clone size in 3D cardiac-tissue whole mounts over a defined timeframe in homeostasis and after infarction. In addition to its use as a surgical tool, ultrasonography can be used to acquire pre-injury and post-injury echocardiographic images to assess cardiac dysfunction mediated by myocardial infarction.