Wall Samuel T, Walker Joseph C, Healy Kevin E, Ratcliffe Mark B, Guccione Julius M
University of California at Berkeley/San Francisco, Joint Graduate Group in Bioengineering, University of California at Berkeley, USA.
Circulation. 2006 Dec 12;114(24):2627-35. doi: 10.1161/CIRCULATIONAHA.106.657270. Epub 2006 Nov 27.
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.
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 (approximately 4.5%) 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.
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.
为了治疗心肌梗死造成的心脏损伤,目前的方法是试图向受损的心室添加细胞和/或合成细胞外基质以恢复功能。由于尚未证实有明确的心肌再生,我们提出从植入材料观察到的心脏变化可能是由心室机制改变所致。
我们利用一个经过验证的患有心尖前梗死的绵羊左心室有限元模型,来研究向左心室壁注射材料的短期效果。对模型的网格和局部材料特性进行修改以模拟预期变化。进行了三组模拟:(1)向前缘区单次注射;(2)治疗性多次边缘区注射;(3)向梗死区域注射材料。结果表明,向边缘区添加材料可使收缩末期纤维应力与添加的分数体积成比例降低,材料越硬,这种衰减效果越好。作为一种潜在的治疗方法,壁体积的微小变化(约4.5%)可将边缘区升高的纤维应力从平均收缩末期水平的28.2 kPa(对照)降低至23.3 kPa(治疗),类似于在远隔区域计算出的22.5 kPa水平。在梗死区域,注射可改善射血分数以及每搏量与舒张末期容积的关系,但对每搏量与舒张末期压力的关系没有影响。
模拟结果表明,向受损的左心室壁添加非收缩性材料对心脏力学有重要影响,可能有益地降低升高的肌纤维应力,同时也会对临床左心室指标产生混杂变化。