Relationship of abnormal intracellular calcium mobilisation to myocyte hypertrophy in human ventricular myocardium.
OBJECTIVE
Calcium transients in muscles from patients with end stage heart failure consist of two components (L1 and L2) at physiological extracellular calcium concentrations ([Ca2+]o); the second component (L2) can appear in normal human myocardium at high [Ca2+]o. In muscles from end stage heart failure patients L2 is associated with significant hypertrophy. To expand these observations a group of muscles from control patients with mild hypertrophy but without overt heart disease was studied (n = 8), in which a second calcium transient component was present during high [Ca2+]o.


METHODS
Using the ratio of the two components of the calcium transient (L2/L1) seen in trabeculae from heart failure patients as a marker of intracellular calcium mobilisation, the hypothesis was tested that the extent of abnormality in transsarcolemmal calcium flux, and/or sarcoplasmic reticular calcium release and reuptake, correlates with the degree of hypertrophy present.


RESULTS
In contrast to non-hypertrophied myocardium, hypertrophied myocardium from patients without heart failure often showed an increase in the L2/L1 ratio at higher [Ca2+]o. Hypertrophied myocardium from patients with failure showed a progressive increase in the L2/L1 ratio, reflecting further impairment of calcium mobilisation. There was a positive correlation between the degree of hypertrophy and calcium mobilisation alterations that was enhanced by raised [Ca2+]o. Altered [Ca2+]i mobilisation may develop early in the course of hypertrophy, before the onset of clinical signs of cardiac dysfunction.
Gwathmey
J K
JK
Cardiovascular Disease Laboratory, Charles A Dana Research Institute, Beth Israel Hospital, Boston, MA 02215.
Bentivegna
L A
LA
Ransil
B J
BJ
Grossman
W
W
Morgan
J P
JP
D000331:Aequorin; D002118:Calcium / Q000378:metabolism*; D006332:Cardiomegaly / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D013997:Time Factors
D000331:Aequorin; D002118:Calcium