Effects of ace inhibition and beta blockade on the distribution of
skeletal muscle fiber types in dogs with moderate heart failure.
Sabbah, Hani N., Hisashi Shimoyama, Victor G. Sharov, Tatsuji Kono,
Ramesh C. Gupta, Michael Lesch, T. Barry Levine, Sidney Goldstein.
Henry Ford Heart and Vascular Institute, Department of Medicine,
Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit,
Michigan,
APStracts 2:0274H, 1995.
In the present study, we examined the effects of early, long-term
monotherapy with the ACE inhibitor, enalapril, and the beta-blocker,
metoprolol, on skeletal muscle (SM) fiber type composition in dogs
with moderate heart failure. The proportion of slow-twitch, fatigue
resistant type-I skeletal muscle fibers is often reduced in heart
failure and may be responsible, in part, for the exercise intolerance
which characterizes this disease state. Left ventricular (LV)
dysfunction was produced in 18 dogs by multiple sequential
intracoronary microembolizations. Embolizations were discontinued
when LV ejection fraction was 30-40%. Subsequently, dogs were
randomized to 3 months oral therapy with enalapril (10 mg twice
daily), metoprolol (25 mg twice daily), or to no therapy at all
(control). Biopsies of the lateral head of the triceps muscle were
obtained at baseline (prior to any embolization), before
randomization and at the completion of 3 months of therapy. Type-I
and type-II SM fibers were differentiated by myofibrillar ATPase (pH
9.4). In untreated dogs, LV ejection fraction decreased during 3
months of follow-up (36+/-1 vs. 26+/-2 %, p<0.05) whereas
treatment with enalapril and metoprolol prevented this decline (36+/
-1 vs. 38+/-4 % and 35+/-1 vs. 39+/-3 % respectively). In untreated
dogs, the proportion of type-I fibers was 27+/-1% before
randomization and decreased to 23+/-1% (p<0.05) at the end of 3
months of follow-up. In dogs treated with enalapril or metoprolol,
the proportion of type-I fibers was 30+/-4% and 28+/-2% before
randomization and 33+/-4% and 30+/-1% respectively after 3 months of
therapy. At the end of therapy, maximal exercise duration was
considerably lower in untreated dogs (15.5+/-2.5 min, n=4) compared
to dogs treated with either enalapril (24.5+/-6.9 min, n=4) or
metoprolol (37.7+/-8.6 min, n=5). We conclude that in dogs with
moderate heart failure, early therapy with enalapril or metoprolol
prevents the progressive decline in the proportion of type-I SM
fibers.
Received 9 March 1995; accepted in final form 23 June 1995.
APS Manuscript Number H227-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 11 July 1995.