Deficient cellular cyclic AMP may cause both cardiac and skeletal muscle dysfunction in heart failure.
Deficient myocardial cyclic AMP concentrations contribute to abnormal Ca2+ handling and systolic and diastolic dysfunction in chronic heart failure (CHF). We tested the hypothesis that decreased cyclic AMP in skeletal muscle of animals with failure may contribute to the weakness and easy fatiguability also common in patients with CHF. We compared intracellular Ca2+ signaling and contractility in skeletal muscle preparations from rats 6 weeks after myocardial infarction-induced CHF versus sham-operated controls. Bundles of 100 to 200 cells were dissected from the extensor digitorum longus (EDL) muscle of control and CHF rats. Muscles from CHF rats exhibited depressed tension development compared with control muscles during twitches. Treatment with 2mM dibutyryl cyclic AMP returned tension and Ca2+ towards normal levels. There was no evidence of cellular atrophy in the CHF rats. In conclusion, EDL skeletal muscle from rats with CHF had intrinsic abnormalities in excitation-contraction coupling that could be reversed with cyclic AMP supplementation as previously reported for the heart. This suggests that deficient cyclic AMP levels may contribute to both cardiac and skeletal muscle dysfunction in CHF.
Grossman
J D
JD
Cardiovascular Division, Beth Israel Hospital, Boston, Massachusetts 02215, USA.
Bishop
A
A
Travers
K E
KE
Perreault
C
C
Woolf
J
J
Hampton
T
T
Rasgado-Flores
H
H
Gonzalez-Serratos
H
H
Morgan
J P
JP
D000818:Animals; D000242:Cyclic AMP / Q000172:deficiency*; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009203:Myocardial Infarction / Q000150:complications; D051381:Rats
D000242:Cyclic AMP