Friedrich S P, Lorell B H, Rousseau M F, Hayashida W, Hess O M, Douglas P S, Gordon S, Keighley C S, Benedict C, Krayenbuehl H P
Charles A. Dana Research Institute, Boston, Mass.
Circulation. 1994 Dec;90(6):2761-71. doi: 10.1161/01.cir.90.6.2761.
Cardiac hypertrophy is associated with elevated intracardiac angiotensin-converting enzyme activity, which may contribute to diastolic dysfunction.
We infused enalaprilat (0.05 mg/min) for 15 minutes into the left coronary arteries of 20 adult patients with left ventricular (LV) hypertrophy due to aortic stenosis (mean aortic valve area, 0.7 +/- 0.2 cm2) and 10 patients with dilated cardiomyopathy (mean ejection fraction, 35 +/- 4%) and assessed (1) simultaneous changes in LV micromanometer pressure and dimensions, (2) LV regional wall motion analyzed by the area method, and (3) Doppler flow-velocity profiles. Systemic neurohormonal activation did not occur with the selective left coronary artery infusion; there were no changes in plasma renin activity, angiotensin-converting enzyme activity, or atrial natriuretic peptide. In patients with aortic stenosis, LV end-diastolic pressure declined from 25 +/- 2 to 20 +/- 2 mm Hg (P < .05). LV pressure-volume and LV pressure-dimension relations showed downward shifts by ventriculography and echocardiography, respectively, indicating improved diastolic distensibility. Regional area change during isovolumic relaxation increased in the anterior segments perfused with enalaprilat but decreased in the inferior segments, indicating acceleration of isovolumic relaxation in the anterior segments and reciprocal shortening in the inferior segments. Regional peak filling rate increased in the anterior segments but not in the inferior segments, and the regional area stiffness constant decreased in the anterior segments but not in the inferior segments. There were no changes in heart rate, cardiac output, or right atrial pressure, excluding alterations in right ventricular/pericardial constraint. In contrast, in the patients with dilated cardiomyopathy the decrease in LV end-diastolic pressure from 22 +/- 2 to 18 +/- 2 mm Hg (P < .05) was accompanied by a significant fall in right atrial pressure (9 +/- 1 to 6 +/- 1 mm Hg), implicating alterations in pericardial constraint. The patients with dilated cardiomyopathy showed no improvement in regional diastolic relaxation, filling, or distensibility.
Intracoronary enalaprilat at a dosage that did not cause systemic neurohormonal activation improved LV diastolic chamber distensibility and regional relaxation and filling in patients with LV hypertrophy due to aortic stenosis. In contrast, these effects of intracoronary enalaprilat on diastolic function were not observed in patients with dilated cardiomyopathy who did not have concentric hypertrophy. These observations support the hypothesis that the cardiac renin-angiotensin system is activated in patients with concentric pressure-overload hypertrophy and that this activation may contribute to impaired diastolic function.
心脏肥大与心内血管紧张素转换酶活性升高有关，这可能导致舒张功能障碍。
我们将依那普利拉（0.05毫克/分钟）注入20例因主动脉瓣狭窄导致左心室（LV）肥大的成年患者（平均主动脉瓣面积为0.7±0.2平方厘米）和10例扩张型心肌病患者（平均射血分数为35±4%）的左冠状动脉内，持续15分钟，并评估：（1）左心室微测压压力和尺寸的同步变化；（2）通过面积法分析的左心室局部室壁运动；（3）多普勒流速剖面。选择性左冠状动脉灌注未引起全身神经激素激活；血浆肾素活性、血管紧张素转换酶活性或心房利钠肽均无变化。在主动脉瓣狭窄患者中，左心室舒张末期压力从25±2毫米汞柱降至20±2毫米汞柱（P<.05）。左心室压力-容积关系和左心室压力-尺寸关系分别通过心室造影和超声心动图显示向下移位，表明舒张期扩张性改善。依那普利拉灌注的前壁节段等容舒张期局部面积变化增加，而下壁节段减少，表明前壁节段等容舒张期加速，下壁节段反向缩短。前壁节段局部峰值充盈率增加，而下壁节段未增加，前壁节段局部面积硬度常数降低，而下壁节段未降低。心率、心输出量或右心房压力无变化，排除了右心室/心包限制的改变。相比之下，在扩张型心肌病患者中，左心室舒张末期压力从22±2毫米汞柱降至18±2毫米汞柱（P<.05），同时右心房压力显著下降（从9±1毫米汞柱降至6±1毫米汞柱），提示心包限制改变。扩张型心肌病患者的局部舒张期松弛、充盈或扩张性未改善。
冠状动脉内给予依那普利拉且剂量未引起全身神经激素激活，可改善因主动脉瓣狭窄导致左心室肥大患者的左心室舒张期腔扩张性及局部松弛和充盈。相比之下，在无向心性肥大的扩张型心肌病患者中未观察到冠状动脉内依那普利拉对舒张功能的这些影响。这些观察结果支持以下假设：向心性压力超负荷肥大患者心脏肾素-血管紧张素系统被激活，且这种激活可能导致舒张功能受损。
