Effects of chronic neutral endopeptidase inhibition on the progression of left ventricular dysfunction and remodeling in dogs with moderate heart failure.
Effects of chronic neutral endopeptidase inhibition on the progression of left ventricular dysfunction and remodeling in dogs with moderate heart failure.
复制标题
慢性中性内肽酶抑制对中度心力衰竭犬左心室功能障碍和重塑的进展的影响。
DOI：
10.1023/a:1020644304771
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发表时间：
2002
影响因子：
3.4
通讯作者：
Sabbah,HaniN
中科院分区：
文献类型：
--
作者：
Mishima,Takayuki;Tanimura,Mitsuhiro;Suzuki,George;Todor,Anastassia;Sharov,VictorG;Tanhehco,ElaineJ;Goldstein,Sidney;Sabbah,HaniN
背景。内源性心房利钠因子（ANF）的利尿作用可能有利于慢性心力衰竭（CHF）的治疗。中性内肽酶（NEP）是负责ANF降解的主要酶。本研究探讨了长期抑制NEP对中度心力衰竭犬左心室功能障碍进展和重构的影响。12只狗连续多次冠状动脉内微栓塞导致左室功能障碍。当左室射血分数（EF）在30-40%之间时停止栓塞。最后一次栓塞后2周，狗被随机分为口服NEP抑制剂ecadotril (100 mg，每日1次，n= 6) 3个月或根本不治疗（对照组，n= 6）。随访3个月，对照组左室EF由37±1%降至28±1% (P< 0.01)，左室舒张末期容积（EDV）和收缩末期容积（ESV）升高（EDV: 72±3 vs 84±5 ml，P< 0.01）；ESV: 45±1 vs. 60±4 ml，P< 0.01)。在使用依卡多曲治疗的犬中，3个月后lvef（34±1% vs. 37±2%）、EDV（79±5 vs. 78±6 ml）和ESV（52±3 vs. 49±4）基本保持不变。研究结束时的组织形态学测量显示，与对照组相比，埃卡多崔可显著减少心肌细胞肥厚。早期，长期用埃卡多曲抑制NEP可防止中度心力衰竭犬的左室功能障碍进展，并减轻左室进行性重构。
Background. The diuretic actions of endogenously produced atrial natriuretic factor (ANF) may be beneficial in the treatment of chronic heart failure (CHF). Neutral endopeptidase (NEP) is the primary enzyme responsible for the degradation of ANF. The present study investigates the effects of long-term NEP inhibition on the progression of left ventricular (LV) dysfunction and remodeling in dogs with moderate heart failure.Methods. LV dysfunction was produced in 12 dogs by multiple sequential intracoronary microembolizations. Embolizations were discontinued when LV ejection fraction (EF) was between 30–40%. Two weeks after the last embolization, dogs were randomized to 3 months of oral therapy with the NEP inhibitor ecadotril (100 mg, once daily,n= 6) or to no therapy at all (control,n= 6).Results. During the 3 months of follow-up, LV EF in control dogs decreased from 37 ± 1% to 28 ± 1% (P< 0.01) and LV end-diastolic volume (EDV) and end-systolic volume (ESV) increased (EDV: 72 ± 3 vs. 84 ± 5 ml,P< 0.01); ESV: 45 ± 1 vs. 60 ± 4 ml,P< 0.01). In dogs treated with ecadotril, LV EF (34 ± 1% vs. 37 ± 2%), EDV (79± 5 vs. 78± 6 ml) and ESV (52 ± 3 vs. 49 ± 4) remained essentially unchanged after 3 months of therapy. Histomorphometric measurements at the termination of the study showed that ecadotril was associated with significantly reduced cardiomyocyte hypertrophy compared to control.Conclusion. Early, long-term NEP inhibition with ecadotril prevents the progression of LV dysfunction and attenuates progressive LV remodeling in dogs with moderate heart failure.