氯沙坦和依那普利治疗心力衰竭后运动耐量的改善：与骨骼肌肌球蛋白重链组成变化的相关性。

Improved exercise tolerance after losartan and enalapril in heart failure: correlation with changes in skeletal muscle myosin heavy chain composition.

作者信息

Vescovo G, Dalla Libera L, Serafini F, Leprotti C, Facchin L, Volterrani M, Ceconi C, Ambrosio G B

机构信息

First Department of Internal Medicine, Venice City Hospital, Venice, Italy.

出版信息

Circulation. 1998 Oct 27;98(17):1742-9. doi: 10.1161/01.cir.98.17.1742.

DOI:10.1161/01.cir.98.17.1742

PMID:9788828

Abstract

BACKGROUND

In congestive heart failure, fatigue-resistant, oxidative, slow type I fibers are decreased in leg skeletal muscle, contributing to exercise capacity (EC) limitation. The mechanisms by which ACE inhibitors and AII antagonists improve EC is still unclear. We tested the hypothesis that improvement in EC is related to changes in skeletal muscle composition toward type I fibers.

METHODS AND RESULTS

Eight patients with congestive heart failure, NYHA classes I through IV, were treated for 6 months with enalapril (E) 20 mg/d, and another 8 with losartan (L) 50 mg/d. EC was assessed with maximal cardiopulmonary exercise testing at baseline and after treatment. Myosin heavy chain (MHC) composition of the gastrocnemius was studied after electrophoretic separation of slow MHC1, fast oxidative MHC2a, and fast glycolytic MHC2b isoforms from needle microbiopsies obtained at baseline and after 6 months. EC improved in both groups. Peak V(O2) increased from 21.0+/-4.7 to 27.6+/-4.3 mL . kg-1 . min -1 (P=0.011) in the L group and from 17.5+/-5.0 to 25.0+/-5.5 mL . kg-1 . min -1 (P=0.014) in the E group. Similarly, ventilatory threshold changed from 15.0+/-4.0 to 19.9+/-4.9 mL (P=0. 049) with L and from 12.0+/-1.9 to 15.4+/-3.5 mL (P=0.039) with E. MCH1 increased from 61.2+/-11.2% to 75.4+/-7.6% with L (P=0.012) and from 60.6+/-13.1% to 80.1+/-10.9% (P=0.006) with E. Similarly, MHC2a decreased from 21.20+/-9.5% to 12.9+/-4.4% (P=0.05) with L and from 19.9+/-7.8% to 11.8+/-7.9% (P=0.06) with E. MHC2b changed from 17. 5+/-6.5% to 11.7+/-5.2% (P=0.07) with L and from 19.5+/-6.4% to 8. 1+/-4.6% (P=0.0015) with E. There was a significant correlation between net changes in MHC1 and absolute changes in peak V(O2) (r2=0.29, P=0.029) and a trend to significance for MHC2a and 2b.

CONCLUSIONS

Six months' treatment with L and with E produces an improvement in EC of similar magnitude. These changes are accompanied by a reshift of MHCs of leg skeletal muscle toward the slow, more fatigue-resistant isoforms. Magnitude of MHC1 changes correlates with the net peak V(O2) gain, which suggests that improved EC may be caused by favorable biochemical changes occurring in the skeletal muscle.

摘要

背景

在充血性心力衰竭中，腿部骨骼肌中抗疲劳、氧化型的慢肌纤维减少，这导致运动能力（EC）受限。血管紧张素转换酶抑制剂（ACE抑制剂）和血管紧张素II拮抗剂改善运动能力的机制仍不清楚。我们检验了这样一个假设，即运动能力的改善与骨骼肌组成向I型纤维的变化有关。

方法与结果

8例纽约心脏协会（NYHA）心功能I至IV级的充血性心力衰竭患者接受依那普利（E）20mg/d治疗6个月，另外8例接受氯沙坦（L）50mg/d治疗。在基线和治疗后通过最大心肺运动试验评估运动能力。从基线和6个月后获得的针吸活检组织中，通过电泳分离慢肌球蛋白重链1（MHC1）、快氧化型肌球蛋白重链2a（MHC2a）和快糖酵解型肌球蛋白重链2b（MHC2b）亚型，研究腓肠肌的肌球蛋白重链（MHC）组成。两组的运动能力均得到改善。L组的峰值摄氧量（V̇O₂）从21.0±4.7增加到27.6±4.3ml·kg⁻¹·min⁻¹（P = 0.011），E组从17.5±5.0增加到25.0±5.5ml·kg⁻¹·min⁻¹（P = 0.014）。同样，L组的通气阈值从15.0±4.0变为19.9±4.9ml（P = 0.049），E组从12.0±1.9变为15.4±3.5ml（P = 0.039）。L组MHC1从61.2±11.2%增加到75.4±7.6%（P = 0.012），E组从60.6±13.1%增加到80.1±10.9%（P = 0.006）。同样，L组MHC2a从21.20±9.5%降至12.9±4.4%（P = 0.05），E组从19.9±7.8%降至11.8±7.9%（P = 0.06）。L组MHC2b从17.5±6.5%变为11.7±5.2%（P = 0.07），E组从19.5±6.4%变为8.1±4.6%（P = 0.0015）。MHC1的净变化与峰值V̇O₂的绝对变化之间存在显著相关性（r² = 0.29，P = 0.029），MHC2a和MHC2b有显著相关趋势。