Improving Delivery of a Biomaterial Payload in Myocardial Infarction

Abstract

Survival after an acute coronary syndrome has greatly improved because of advances in thrombolytic therapy, stabilization of the culprit lesion such as with coronary stents, and the use of pharmacological approaches to prevent recurrent thrombotic and arrhythmic events. Despite these approaches, however, myocardial injury culminating in myocardial infarction (MI) continues to be an all too common sequela. The MI region is a highly heterogeneous structure that contains several cell types, such as residual cardiac myocytes, inflammatory cells of different lineages, proliferating and transdifferentiating fibroblasts, and extracellular matrix proteins and signaling molecules. Although canonical thought was that the MI region was a rather static, fibrotic structure, it is now clear that this is a dynamic and ever-evolving entity with changes in geometry, biophysical properties, and cellular/extracellular composition. The time course and extent of these post-MI processes have been generically termed post-MI remodeling and is recognized as a milestone event for the initiation and progression to left ventricular (LV) dilation and dysfunction. One ubiquitous feature of post-MI remodeling is a progressive thinning and dyskinesia of the MI region, which is because of the summation of several factors: a loss of cardiac myocytes and thus functional myocardium, continuous turnover and instability of the extracellular matrix, and significant shifts in stress–strain patterns within this region throughout the cardiac cycle. Specifically, significant heterogeneity arises in the stress–strain patterns both within and surrounding the MI region and in turn can contribute to a feed-forward process of continuous activation of bioactive molecules and extracellular matrix instability. These biomechanical changes result in continued MI thinning and recruitment of border zone myocardium into the MI region, which is defined as MI expansion. As the MI expansion process continues in an inexorable fashion, the degree of heterogeneity in stress–strain relations are exacerbated, bulging of the MI region becomes evident by …