Litwin S E, Katz S E, Weinberg E O, Lorell B H, Aurigemma G P, Douglas P S
Charles A. Dana Research Institute, Beth Israel Hospital, Boston, Mass., USA.
Circulation. 1995 May 15;91(10):2642-54. doi: 10.1161/01.cir.91.10.2642.
Although chronic pressure overload may progress to left ventricular (LV) failure, the pathophysiology of this transition is not well understood. In addition, the effects of chronic angiotensin-converting enzyme (ACE) inhibition on this transition are largely undefined.
To examine changes in LV structure and function during the transition to heart failure, rats with LV hypertrophy due to banding of the ascending aorta (LVH, n = 22) and age-matched sham-operated rats (n = 6) were studied 6, 12, and 18 weeks after aortic banding. Two-dimensionally guided transthoracic M-mode echocardiograms and transmitral Doppler spectra were recorded for assessment of LV geometry and systolic and diastolic functions. LVH rats were randomized to no treatment (n = 10) or treatment with the ACE inhibitor fosinopril (50 mg/kg per day, n = 12) after the baseline echocardiogram. Six weeks after banding, LVH rats had increased LV wall thickness with normal cavity dimensions and supranormal endocardial systolic shortening. However, midwall shortening was mildly depressed, and a restrictive diastolic filling pattern was present. After 18 weeks of untreated pressure overload, LV wall thickness was unchanged, but cavity dilation, a fall in endocardial shortening, and further deterioration of diastolic filling were evident. In contrast to untreated LVH rats, the fosinopril-treated rats showed no change in LV diastolic cavity dimension, and systolic and diastolic functions did not deteriorate or improved. Closed chest LV systolic pressures at 18 weeks were not different in LVH or LVH-fosinopril rats (197 versus 198 mm Hg), although end-diastolic pressure was higher in the untreated rats (18 versus 11 mm Hg). Calculated LV systolic wall stress was lower in fosinopril-treated than untreated LVH rats. The severity of LV diastolic filling abnormalities correlated strongly with operating LV chamber stiffness (r = .88, P < .0001).
This model of pressure overload is characterized initially by concentric LV hypertrophy with compensated LV chamber performance; however, markedly abnormal diastolic filling is present. The transition from compensated hypertrophy to early failure is heralded by LV dilation, impairment of systolic function, and progression of the abnormalities in LV filling. Chronic ACE inhibition in rats with supravalvular aortic banding (1) does not change in vivo LV systolic pressure but prevents increased LV cavity size and increased LV wall stress and (2) attenuates impairment of (or improves) both systolic and diastolic functions. The effects of fosinopril could be explained in part by inhibition of an intracardiac renin-angiotensin system.
尽管慢性压力超负荷可能进展为左心室（LV）衰竭，但这种转变的病理生理学尚未完全了解。此外，慢性血管紧张素转换酶（ACE）抑制对这种转变的影响在很大程度上尚不明确。
为了研究向心力衰竭转变过程中左心室结构和功能的变化，对因升主动脉缩窄导致左心室肥厚的大鼠（LVH，n = 22）和年龄匹配的假手术大鼠（n = 6）在主动脉缩窄后6、12和18周进行了研究。记录二维引导的经胸M型超声心动图和二尖瓣多普勒频谱，以评估左心室几何形状以及收缩和舒张功能。在基线超声心动图检查后，将LVH大鼠随机分为不治疗组（n = 10）或用ACE抑制剂福辛普利治疗组（每天50 mg/kg，n = 12）。缩窄后6周，LVH大鼠左心室壁厚度增加，腔室尺寸正常，心内膜收缩期缩短超常。然而，中层壁缩短轻度降低，并且存在限制性舒张期充盈模式。在未经治疗的压力超负荷18周后，左心室壁厚度未改变，但腔室扩张、心内膜缩短下降以及舒张期充盈进一步恶化明显。与未经治疗的LVH大鼠相比，福辛普利治疗的大鼠左心室舒张腔室尺寸没有变化，收缩和舒张功能没有恶化或有所改善。尽管未治疗大鼠的舒张末期压力较高（18对11 mmHg），但LVH或LVH-福辛普利大鼠在18周时的闭式胸腔左心室收缩压没有差异（197对198 mmHg）。福辛普利治疗的LVH大鼠计算出的左心室收缩壁应力低于未治疗的大鼠。左心室舒张期充盈异常的严重程度与左心室腔室僵硬度密切相关（r = 0.88，P <.0001）。
这种压力超负荷模型最初的特征是同心性左心室肥厚伴左心室腔室功能代偿；然而，存在明显异常的舒张期充盈。从代偿性肥厚向早期衰竭的转变以左心室扩张、收缩功能受损以及左心室充盈异常的进展为标志。对主动脉瓣上缩窄大鼠进行慢性ACE抑制（1）不会改变体内左心室收缩压，但可防止左心室腔室大小增加和左心室壁应力增加，并且（2）减轻（或改善）收缩和舒张功能损害。福辛普利的作用部分可以通过抑制心内肾素-血管紧张素系统来解释。
