Copyright © 1998 by the European Society of Cardiology.
A non-invasive selective assessment of type I fibre mitochondrial function using31PNMR spectroscopy
Evidence for impaired oxidative phosphorylation rate in skeletal muscle in patients with chronic heart failure
a Sticares Foundation, Rotterdam, The Netherlands
b Laboratory of Metabolic Diseases, University Children’s Hospital, Utrecht, The Netherlands
c Streekziekenhuis De Honte, Terneuzen, The Netherlands
d Academisch Ziekenhuis Vrije, Amsterdam, The Netherlands
accepted July 10, 1997
Background Skeletal muscle abnormalities contribute considerably to the clinical expression of heart failure. Deconditioning, underperfusion and an increased number of type IIb glycolytical fibres lead to early lactate production and muscle fatigue at low exercise levels. Aerobic muscle metabolism may also be impaired, as suggested by biopsy studies. Thus far, no data are available from non-invasive studies to indicate the extent of aerobic muscle dysfunction during low-grade exercise which does not induce acidosis.
Methods and results Mitochondrial function of skeletal muscle during fibre type I activation was studied in 22 patients with chronic heart failure [NYHA class III, left ventricular ejection fraction 28±2%, (patients)] on ACE inhibitors, diuretics and digoxin, and in 20 normal subjects, using31PNMR spectroscopy of a single right forearm flexor muscle during three mild intermittent exercise levels (0–40% of maximum voluntary contraction) and recovery time. At rest, the inorganic phosphate/phosphocreatine ratio was different [0·13±0·005 (patients) vs 0·09±0·002 (normal subjects),P=0·0001]. However, intracellular pH was comparable. Local acidosis (tissue pH <6·9) was avoided to prevent fibre type IIb activation. Calculated resting phosphate potential levels were comparable, but the slope and intercept of the linear relationship of phosphate potential and workload were significantly lower in patients than in normal subjects (11·7±0·7 vs 15·8±0·6 and 139±7 vs 196±7, patients vs normal subjects, indicating early exhaustion of intracellular energy at lower exercise levels. Also, maximum calculated workload at which tissue ADP stabilized was lower in patients than in normal subjects (88±7% vs 120±4% of maximum voluntary workload, patients vs normal subjects,P<0·05). Time to recovery to pre-test phosphocreatine levels was prolonged by 46% in patients compared to normal subjects (P<0·05).
Conclusions In heart failure, oxidative fibre mitochondrial function in skeletal muscle is impaired, as reflected by the reduced phosphate potential and oxidative phosphorylation rate, early exhaustion and slowed recovery of intracellular energy reserve at workloads, which do not affect intracellular pH.
Key Words: Heart failure • mitochondrial function • 31PNMR spectroscopy • skeletal muscle • phosphorylation rate • muscle fibre type
f1 Correspondence: W. J. Remme, MD, PhD, Sticares Foundation, P.O. Box 52006, 3007 LA Rotterdam, The Netherlands.
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