Dabiri Yaghoub, Sack Kevin L, Shaul Semion, Acevedo-Bolton Gabriel, Choy Jenny S, Kassab Ghassan S, Guccione Julius M
Department of Surgery, University of California San Francisco, San Francisco, California, USA.
California Medical Innovations Institute, San Diego, California, USA.
Mol Cell Biomech. 2019;16(3):185-197. doi: 10.32604/mcb.2019.07364.
We hypothesized that minimally invasive injections of a softening agent at strategic locations in stiff myocardium could de-stiffen the left ventricle (LV) globally. Physics-based finite element models of the LV were created from LV echocardiography images and pressures recorded during experiments in four swine. Results confirmed animal models of LV softening by systemic agents. Regional de-stiffening of myocardium led to global de-stiffening of LV. The mathematical set up was used to design LV global de-stiffening by regional softening of myocardium. At an end diastolic pressure of 23 mmHg, when 8 ml of the free wall was covered by intramyocardial injections, end diastolic volume (EDV) increased by 15.0%, whereas an increase up to 11 ml due to intramyocardial injections in the septum and free wall led to a 26.0% increase in EDV. Although the endocardial intramyocardial injections occupied a lower LV wall volume, they led to an EDV (44 ml) that was equal compared to intramyocardial injections in the mid-wall (44 ml) and larger compared to intramyocardial injections in the epicardium (41 ml). Using an in silico set up, sites of regional myocardium de-stiffening could be planned in order to globally soften overly stiff LV in heart failure with preserved ejection fraction. This novel treatment is built on subject-specific data. Hypothesis-testing of these simulation findings in animal models is warranted.
我们假设，在僵硬心肌的关键部位微创注射软化剂可使左心室（LV）整体软化。利用4头猪实验期间记录的左室超声心动图图像和压力数据，建立了基于物理的左室有限元模型。结果证实了全身用药使左室软化的动物模型。心肌局部软化导致左室整体软化。该数学模型用于设计通过心肌局部软化实现左室整体软化的方法。在舒张末期压力为23 mmHg时，当心肌内注射覆盖8 ml游离壁时，舒张末期容积（EDV）增加15.0%，而当心肌内注射到室间隔和游离壁的量增加至11 ml时，EDV增加26.0%。尽管心内膜下心肌内注射占据的左室壁容积较小，但它们导致的EDV（44 ml）与中层心肌内注射（44 ml）相当，且比心外膜下心肌内注射（41 ml）更大。利用计算机模拟设置，可以规划心肌局部软化的部位，以整体软化射血分数保留的心力衰竭中过度僵硬的左室。这种新疗法基于个体特异性数据。有必要在动物模型中对这些模拟结果进行假设检验。
