IMPAIRED CA2-OVERLOAD HYPERTROPHY IN RAT HEARTS( HANDLING IS AN EARLYMANIFESTATION OF PRESSURE)

Both cytosolic free Ca2+ ([Ca2+](i)) decline and myocardial relaxation are slowed in severe hypertrophy and heart failure. However, it is no t certain whether this occurs in mild to moderate hypertrophy. Therefo re, we tested the hypotheses that slowing of [Ca2+](i) decline 1) occu rs in mild to moderate hypertrophy, 2) occurs in the absence of slowed relaxation, and 3) is related to the degree of hypertrophy Experiment s were performed on isolated rat hearts subjected to pressure overload . Indo 1 fluorescence was used as an index of [Ca2+](i). [Ca2+](i) dec line and myocardial relaxation were assessed by the time constant of e xponential [Ca2+](i) decline (tau(Ca)) and left ventricular (LV) press ure decline (tau(p)), respectively. Mean tau(Ca) was significantly inc reased in hearts from banded rats compared with sham-operated rats (59 +/- 13 vs. 45 +/- 5 ms, P = 0.03). In contrast, there was no differen ce in mean tau p (28 +/- 3 vs. 29 +/- 5 ms, P = not significant). Ther e was a linear relationship between tau(Ca) and LV dry weight (r = 0.7 9). In summary, slowing of the [Ca2+](i) transient decline occurred in mild to moderate hypertrophy. However, LV relaxation was unaffected. Furthermore, slowing of the [Ca2+](i) transient decline was closely re lated to the degree of LV hypertrophy. These data suggest that slowing of [Ca2+](i) decline is an early manifestation of pressure-overload h ypertrophy that precedes slowing of relaxation.