Davison G, Hall C S, Miller J G, Scott M, Wickline S A
Department of Physics, Washington University School of Medicine, St Louis, MO 63110.
Circulation. 1994 Sep;90(3):1334-42. doi: 10.1161/01.cir.90.3.1334.
Although angiotensin-converting enzyme (ACE) inhibitors have become a mainstay of treatment for chronic congestive heart failure (CHF), it is not known whether the cardiac remodeling effects are a secondary phenomenon, resulting from ACE inhibitors' hemodynamic actions of afterload reduction, or occur through an independent mechanism.
We used ultrasonic tissue characterization to define potentially salutary effects of treatment with ACE inhibitors on the material properties of the heart and its potential influence on cardiac remodeling at the cellular level. Ten 1-month-old, cardiomyopathic (CM) Syrian hamsters and 6 normal (NL) hamsters were treated with captopril (2 g/L water ad libitum), and 10 CM hamsters and 10 NL hamsters were maintained untreated for 3 months. Hearts were excised, and backscattered radiofrequency data were acquired from 1200 independent sites from each specimen with a high-resolution 50-MHz acoustic microscope for calculation of integrated backscatter (IB). Treatment with captopril reduced left ventricular mass, calcium concentration, and IB in CM hearts without affecting myofiber size or collagen concentration. The IB from grossly normal regions of myocardium in NL hamsters, treated CM hamsters, and untreated CM hamsters was not significantly different. The IB from the microscopic regions of scar tissue in treated CM hamsters was significantly less (P = .0004) than that from scar tissue in untreated CM hamsters.
The reduced IB from treated scar tissue components reflects specific alterations in the material properties (elastic stiffness, density) of fibrous regions in CM hearts induced by captopril. This is the first report that defines specific cellular effects of ACE inhibitors on the material properties of isolated components of cardiac tissue in experimental cardiomyopathy. These alterations in material properties of scar tissue components represent a potential mechanism for the salutary actions of ACE inhibitors in heart failure.
尽管血管紧张素转换酶（ACE）抑制剂已成为慢性充血性心力衰竭（CHF）治疗的主要手段，但尚不清楚其心脏重塑作用是继发于ACE抑制剂降低后负荷的血流动力学作用，还是通过独立机制发生。
我们使用超声组织特征分析来确定ACE抑制剂治疗对心脏材料特性的潜在有益作用及其对细胞水平心脏重塑的潜在影响。10只1月龄的心肌病（CM）叙利亚仓鼠和6只正常（NL）仓鼠用卡托普利（2 g/L水，随意饮用）治疗，10只CM仓鼠和10只NL仓鼠未治疗，维持3个月。切除心脏，使用高分辨率50-MHz声学显微镜从每个标本的1200个独立部位采集背向散射射频数据，以计算背向散射积分（IB）。卡托普利治疗可降低CM心脏的左心室质量、钙浓度和IB，而不影响肌纤维大小或胶原浓度。NL仓鼠、治疗后的CM仓鼠和未治疗的CM仓鼠心肌大体正常区域的IB无显著差异。治疗后的CM仓鼠瘢痕组织微观区域的IB显著低于未治疗的CM仓鼠瘢痕组织（P = 0.0004）。
治疗后瘢痕组织成分的IB降低反映了卡托普利诱导的CM心脏纤维区域材料特性（弹性硬度、密度）的特定改变。这是第一份定义ACE抑制剂对实验性心肌病心脏组织分离成分材料特性的特定细胞作用的报告。瘢痕组织成分材料特性的这些改变代表了ACE抑制剂在心力衰竭中有益作用的潜在机制。
