Theoretical Impact of the Injection of Material Into the Myocardium

Abstract

Background-To treat cardiac injuries created by myocardial infarcts, current approaches seek to add cells and/or synthetic extracellular matrices to the damaged ventricle to restore function. Because definitive myocardial regeneration remains undemonstrated, we propose that cardiac changes observed from implanted materials may result from altered mechanisms of the ventricle. Methods and Results-We exploited a validated finite element model of an ovine left ventricle with an anteroapical infarct to examine the short-term effect of injecting material to the left ventricular wall. The model's mesh and regional material properties were modified to simulate expected changes. Three sets of simulations were run: (1) single injection to the anterior border zone; (2) therapeutic multiple border zone injections; and (3) injection of material to the infarct region.Results indicate that additions to the border zone decrease end-systolic fiber stress proportionally to the fractional volume added, with stiffer materials improving this attenuation. As a potential therapy, small changes in wall volume (Ϸ4.5%) reduce elevated border zone fiber stresses from mean end-systole levels of 28.2 kPa (control) to 23.3 kPa (treatment), similar to levels of 22.5 kPA computed in remote regions. In the infarct, injection improves ejection fraction and the stroke volume/end-diastolic volume relationship but has no effect on the stroke volume/end-diastolic pressure relationship. Conclusions-Simulations indicate that the addition of noncontractile material to a damaged left ventricular wall has important effects on cardiac mechanics, with potentially beneficial reduction of elevated myofiber stresses, as well as confounding changes to clinical left ventricular metrics.

Injectable Acellular Hydrogels for Cardiac Repair

“…More specifically, they demonstrated that injections of 4.5% of the LV wall volume and 20% of the stiffness of the natural myocardium into the BZ were able to decrease the fiber stress by 20% compared to control simulations with no injections. Other approaches have validated the importance of infarct compliance using FE, as well as lumpparameter models; results reveal similar overall beneficial outcomes [35,65,66]. FE models have also been employed to evaluate the effects of material volume and distribution in the myocardium and showed that they influence the extent of remodeling, depending on their pattern of injection (Fig.…”

“…Over the past decade, it has become clear that the mechanical changes that occur after MI must be considered when developing post-MI therapies [35,41,42]. MI leads to extracellular matrix (ECM) breakdown and results in geometric changes in both the infarcted and healthy myocardium.…”

“…Theoretical models have implied that material properties, specifically mechanics and volume, are important to consider when selecting the type of bulking agent to ameliorate dilation and increased stress in the myocardial wall [35,[65][66][67]. Using a finite element (FE) model to simulate the effects of injecting a non-contractile material into the myocardium, Wall et al showed that bulking the myocardium was sufficient to attenuate post-MI geometric changes and, thus, decrease stress in the myocardial wall [35].…”

“…Using a finite element (FE) model to simulate the effects of injecting a non-contractile material into the myocardium, Wall et al showed that bulking the myocardium was sufficient to attenuate post-MI geometric changes and, thus, decrease stress in the myocardial wall [35]. More specifically, they demonstrated that injections of 4.5% of the LV wall volume and 20% of the stiffness of the natural myocardium into the BZ were able to decrease the fiber stress by 20% compared to control simulations with no injections.…”

“…However, these approaches are limited by the invasive procedure in which they are applied, and clinical adoption has not occurred. In order to circumvent the invasive surgical placement of restraining devices early post-MI, our group and others have begun to explore the use of injectable materials, and specifically hydrogels, to limit infarct expansion and normalize the regional stress distribution [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35].…”