Alterations in heart failure of cyclic AMP-dependent inotropic and lusitropic properties of cardiac and skeletal muscle.
A central working hypothesis in our laboratory is that deficient cellular cyclic AMP concentrations may be responsible, at least in part, for striated muscle dysfunction, both cardiac and skeletal, in heart failure. These results suggest that therapy aimed at restoring cyclic AMP to normal levels may be effective with regard to improving systolic and diastolic function in the heart and may decrease the development of fatigue in skeletal muscle of patients with failure. The use of cyclic AMP-dependent drugs in clinical practice has been limited by side effects associated with raising total cellular content of this cyclic nucleotide. However, evidence suggesting that separate pools of cyclic AMP may exist within the cell raises the possibility that those pools associated with excitation/contraction coupling could serve as more specific therapeutic targets.
Bishop
A
A
Charles A. Dana Research Institute, Boston, Massachusetts, USA.
Travers
K E
KE
Grossman
J
J
Johnson
H
H
Perreault
C
C
Woolf
J H
JH
Cittadini
A
A
Gonzalez-Serratos
H
H
Morgan
J P
JP
D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D006321:Heart / Q000502:physiology / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology / Q000503:physiopathology*; D009200:Myocardial Contraction / Q000502:physiology*
D000242:Cyclic AMP