Effects of ACE inhibition and beta-blockade on skeletal muscle fiber types in dogs with moderate heart failure.
The proportion of slow-twitch, fatigue-resistant type 1 skeletal muscle (SM) fibers is often reduced in heart failure (HF), while the proportion of fatigue-sensitive type-II fibers increases. This maladaptation may be partially responsible for the exercise intolerance that characterize HF. In this study, we examined the effects of early monotherapy with the angiotensin-converting enzyme inhibor, enalapril, and the beta-blocker, metoprolol, on SM fiber type composition in 18 dogs with moderate HF produced by intracoronary microembolizations. HF dogs were randomized to 3 mo therapy with enalapril (10 mg twice daily), metoprolol (25 mg twice daily), or no treatment. Triceps muscle biopsies were obtained at baseline, before randomization, and at the end of 30 mo of therapy. Type I and type II SM fibers were differentiated by myofibrillar adenosinetriphosphatase (pH 9.4). 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 mo 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 33 +/- 1%, respectively, after 3 mo of therapy. In conclusion, in dogs with moderate HF, early therapy with enalapril or metoprolol prevents the progressive decline in the proportion of type I SM fibers.
Sabbah
H N
HN
Henry Ford Heart and Vascular Institute, Department of Medicine, Henry Ford Hospital, Detroit, Michigan 48202, USA.
Shimoyama
H
H
Sharov
V G
VG
Kono
T
T
Gupta
R C
RC
Lesch
M
M
Levine
T B
TB
Goldstein
S
S
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002303:Cardiac Output, Low / Q000473:pathology* / Q000503:physiopathology; D004285:Dogs; D004656:Enalapril / Q000494:pharmacology; D005260:Female; D005552:Forelimb; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D010807:Physical Endurance; D005082:Physical Exertion
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D008790:Metoprolol