The mechanical response of intact blood vessels to applied loads can be delineated into passive and active components using an isometric decomposition approach. Whereas the passive response is due predominantly to the extracellular matrix (ECM) proteins and amorphous ground substance, the active response depends on the presence of smooth muscle cells (SMCs) and the contractile machinery activated within those cells. To better understand determinants of active stress generation within the vascular wall, we subjected porcine common carotid arteries (CCAs) to biaxial inflation-extension testing under maximally contracted or passive SMC conditions and semiquantitatively measured two known markers of the contractile SMC phenotype: smoothelin and smooth muscle-myosin heavy chain (SM-MHC). Using isometric decomposition and established constitutive models, an intuitive but novel correlation between the magnitude of active stress generation and the relative abundance of smoothelin and SM-MHC emerged. Our results reiterate the importance of stretch-dependent active stress generation to the total mechanical response. Overall these findings can be used to decouple the mechanical contribution of SMCs from the ECM and is therefore a powerful tool in the analysis of disease states and potential therapies where both constituent are altered.

Cardiovascular disease, particularly the occurrence of myocardial infarction (MI), remains a leading cause of morbidity and mortality (Go et al., 127: e6-e245, 2013; Go et al. 129: e28-e292, 2014). There is growing recognition that a key factor for post-MI outcomes is adverse remodeling and changes in the regional structure, composition, and mechanical properties of the MI region itself. However, in vivo assessment of regional mechanics post-MI can be confounded by the species, temporal aspects of MI healing, as well as size, location, and extent of infarction across myocardial wall. Moreover, MI regional mechanics have been assessed over varying phases of the cardiac cycle, and thus, uniform conclusions regarding the material properties of the MI region can be difficult. This review assesses past studies that have performed in vivo measures of MI mechanics and attempts to provide coalescence on key points from these studies, as well as offer potential recommendations for unifying approaches in terms of regional post-MI mechanics. A uniform approach to biophysical measures of import will allow comparisons across studies, as well as provide a basis for potential therapeutic markers.

Using different TIMP-3 formulations, when injected into the MI region, slowed the progression of indices of LV failure, suggesting that the N terminus of TIMP-3 is sufficient to attenuate early adverse functional events post-MI. The F-TIMP-3 injections but not N-TIMP-3 injections reduced relative indices of inflammation at the mRNA level, suggesting that the C-terminus region affects other biological pathways. These unique proof of concept studies demonstrate the feasibility of using recombinant small molecules to selectively interrupt adverse LV remodeling post-MI.

Following myocardial infarction (MI), detrimental changes to the geometry, composition, and mechanical properties of the left ventricle (LV) are initiated in a process generally termed adverse post-MI remodeling. Cumulatively, these changes lead to a loss of LV function and are deterministic factors in the progression to heart failure. Proposed therapeutic strategies to target aberrant LV mechanics post-MI have shown potential to stabilize LV functional indices throughout the remodeling process. The in vivo quantification of LV mechanics, particularly within the MI region, is therefore essential to the continued development and evaluation of strategies to interrupt the post-MI remodeling process. The present study utilizes a porcine MI model and in vivo sonomicrometry to characterize MI region stiffness at 14 days post-MI. Obtained results demonstrate a significant dependence of mechanical properties on location and direction within the MI region, as well as cardiac phase. While approaches for comprehensive characterization of LV mechanics post-MI still need to be improved and standardized, our findings provide insight into the issues and complexities that must be considered within the MI region itself.

The unique findings from this study are 2-fold. First, targeting the MI region following the resolution of the acute event using a localized stimulation approach is feasible. Second, localized stimulation modified a key parameter of adverse post-MI remodeling (dilation) and progression to heart failure. These findings demonstrate that the MI region itself is a modifiable tissue and responsive to localized electrical stimulation.