Pathophysiology of cardiac hypertrophy and failure of human working myocardium: abnormalities in calcium handling.
Abnormal intracellular calcium ([Ca2+]i) handling appears to be a major cause of both systolic and diastolic dysfunction in animals and human beings with hypertrophy and/or heart failure. We utilized the bioluminescent calcium indicator aequorin to examine the cyclical variations in intracellular calcium levels during isometric contractions. Studies of ventricular muscle from patients with end-stage heart failure exhibited three physiologic findings not seen in preparations taken from normal hearts including: 1) abnormalities in calcium handling; 2) deficient production of cyclic AMP; and 3) a reversed force-frequency relationship. These observations have important implications with regard to the pathogenesis and therapeutics of heart failure in man.
Meuse
A J
AJ
Charles A. Dana Research Institute, Harvard-Thorndike Laboratory, Boston, Massachusetts.
Perreault
C L
CL
Morgan
J P
JP
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006332:Cardiomegaly / Q000503:physiopathology*; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D000242:Cyclic AMP / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology*; D006801:Humans
D000242:Cyclic AMP; D002118:Calcium