From the First Department of Internal Medicine, Venice City Hospital,
Venice, Italy (G.V., F.S., C.L., G.B.A.); the CNR Unit for Muscle
Physiopathology, University of Padua, Padua, Italy (L.D.L.); the Department of
Cardiology, Venice City Hospital, Venice, Italy (L.F.); and Cardiology and
IRCCS, Gussago, Brescia, Italy (M.V., C.C.).
Correspondence to Giorgio Vescovo, MD, PhD, FESC, First Department of Internal Medicine, Venice City Hospital, 30100 Venice, Italy. E-mail ldl{at}civ.bio.unipd.it
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
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
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Improved Exercise Tolerance After Losartan and Enalapril in Heart Failure
Correlation With Changes in Skeletal Muscle Myosin Heavy Chain Composition
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
O2
(r2=0.29, P=0.029) and a
trend to significance for MHC2a and 2b. O2
gain, which suggests that improved EC may be caused by favorable
biochemical changes occurring in the skeletal muscle.
Key Words: heart failure • muscles • myosin • exercise
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