TY - JOUR
T1 - Diastolic dysfunction in hypertrophic cardiomyopathy
T2 - Effect on active force generation during systole
AU - Gwathmey, Judith K.
AU - Warren, Sanford E.
AU - Maurice Briggs, G.
AU - Copelas, Linda
AU - Feldman, Marc D.
AU - Phillips, Preston J.
AU - Callahan, Mark
AU - Schoen, Frederick J.
AU - Grossman, William
AU - Morgan, James P.
PY - 1991
Y1 - 1991
N2 - We tested the hypothesis that intracellular Ca++ ([Ca++]i]) over-load underlies the diastolic dysfunction of patients with hypertrophic cardiomyopathy. Myocardial tissue was obtained at the time of surgery or transplantation from patients with hypertrophic cardiomyopathy and was compared with control myocardium obtained from patients without heart disease. The isometric contractions and electrophysiologic properties of all myocardial specimens were recorded by standard techniques and |Ca++], was measured with the bioluminescent calcium indicator aequorin. In contrast to the controls, action potentials, Ca++ transients, and isometric contraction and relaxation were markedly prolonged in the hypertrophic myocardium, and the Ca++ transients consisted of two distinct components. At 38°C and 1 Hz pacing frequency, a state of relative Ca++ overload appeared to develop, which produced a rise in end-diastolic [Ca++]I, incomplete relaxation, and fusion of twitches with a resultant decrease in active tension development. We also found that drugs which increase [Ca++]i, such as digitalis, exacerbated these abnormalities, whereas drugs that lower [Ca++]i, such as verapamil, or agents that increase cyclic AMP, such as forskolin, prevented them. These results may explain why patients with hypertrophie cardiomyopathy tolerate tachycardia poorly, and may have important implications with regard to the pharmacologic treatment of patients with hypertrophie cardiomyopathy. (J. Clin. Invest. 1991, 87:1023-1031.).
AB - We tested the hypothesis that intracellular Ca++ ([Ca++]i]) over-load underlies the diastolic dysfunction of patients with hypertrophic cardiomyopathy. Myocardial tissue was obtained at the time of surgery or transplantation from patients with hypertrophic cardiomyopathy and was compared with control myocardium obtained from patients without heart disease. The isometric contractions and electrophysiologic properties of all myocardial specimens were recorded by standard techniques and |Ca++], was measured with the bioluminescent calcium indicator aequorin. In contrast to the controls, action potentials, Ca++ transients, and isometric contraction and relaxation were markedly prolonged in the hypertrophic myocardium, and the Ca++ transients consisted of two distinct components. At 38°C and 1 Hz pacing frequency, a state of relative Ca++ overload appeared to develop, which produced a rise in end-diastolic [Ca++]I, incomplete relaxation, and fusion of twitches with a resultant decrease in active tension development. We also found that drugs which increase [Ca++]i, such as digitalis, exacerbated these abnormalities, whereas drugs that lower [Ca++]i, such as verapamil, or agents that increase cyclic AMP, such as forskolin, prevented them. These results may explain why patients with hypertrophie cardiomyopathy tolerate tachycardia poorly, and may have important implications with regard to the pharmacologic treatment of patients with hypertrophie cardiomyopathy. (J. Clin. Invest. 1991, 87:1023-1031.).
KW - Calcium indicators
KW - Cyclic adenosine monophosphate
KW - Diastolic dysfunction, hypertrophic cardiomyopathy
KW - Sarcoplasmic reticulum
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U2 - 10.1172/JCI115061
DO - 10.1172/JCI115061
M3 - Article
C2 - 1999483
AN - SCOPUS:0025763608
VL - 87
SP - 1023
EP - 1031
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 3
ER -