IMPROVED EXERCISE TOLERANCE AFTER LOSARTAN AND ENALAPRIL IN HEART-FAILURE - CORRELATION WITH CHANGES IN SKELETAL-MUSCLE MYOSIN HEAVY-CHAIN COMPOSITION

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 inhi bitors and AII antagonists improve EC is still unclear. We tested the hypothesis that improvement in EC is related to changes in skeletal mu scle composition toward type I fibers. Methods and Results-Eight patie nts with congestive heart failure, NYHA classes I through IV, were tre ated for 6 months with enalapril (E) 20 mg/d, and another 8 with losar tan (L) 50 mg/d. EC was assessed with maximal cardiopulmonary exercise testing at baseline and after treatment. Myosin heavy chain (MHC) com position of the gastrocnemius was studied after electrophoretic separa tion of slow MHC1, fast oxidative MHC2a, and fast glycolytic MHC2b iso forms from needle microbiopsies obtained at baseline and after 6 month s. EC improved in both groups. Peak (V) over dotO(2) 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 t he E group. Similarly, ventilatory threshold changed from 15.0+/-4.0 t o 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. S imilarly, MHC2a decreased from 21.20+/-9.5% to 12.9+/-4.4% (P=0.05) wi th L and from 19.5+/-7.9% to 11.8+/-7.9% (P=0.06) with E. MHC2b change d 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) over dotO (2) (r(2)=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 impro vement in EC of similar magnitude. These changes are accompanied by a reshift of MHCs of leg skeletal muscle toward the slow, more fatigue-r esistant isoforms. Magnitude of MHC1 changes correlates with the net p eak (V) over dotO(2) gain, which suggests that improved EC;may be caus ed by favorable biochemical changes occurring in the skeletal muscle.