Impaired cell shortening and relengthening with increased pacing frequencyare intrinsic to the senescent mouse cardiomyocyte

Increased heart rate enhances cardiac contractility and accelerates relaxat ion. Both the force- and relaxation-frequency relationships are critical to myocardial function, especially during stress, and have been shown to be i mpaired in senescent myocardium. While senescent myocardium is characterize d by decreased sarcoplasmic reticulum calcium ATPase activity it is unclear if altered calcium regulation is directly responsible for the attenuated c ontractility and relaxation observed with increasing pacing frequency in ag ed myocardium. We examined this issue using freshly dissociated left ventricular myocytes, isolated from young adult and senescent mouse hearts. Myocytes were paced from 2 to 9 Hz at 37 degreesC, and cell shortening and [Ca2+](i) were simul taneously measured using video edge-detection and fura-2 fluorescence, resp ectively. In adult myocytes, increasing the pacing rate resulted in a progr essive increase in percent cell shortening (CS) (P<0.01). This positive CS- frequency relationship was paralleled by an increase in [Ca2+](i) transient amplitude (P<0.05). In contrast, the CS-frequency relationship was blunted in senescent myocytes with no increase in percent CS or [C-a2+](i) transie nt amplitude with increasing pacing rate. With increased pacing, the decrea ses in time constants (tau) of cell relengthening and Ca2+ transient decay were much steeper in adult compared to senescent myocytes (P<0.05). This study demonstrates that adult mouse myocytes exhibit augmented intrace llular Ca2+ transient amplitude and enhanced intracellular Ca2+ removal wit h increasing pacing frequency, resulting in increased cell shortening and e nhanced relengthening with frequency. In contrast, senescent mouse myocytes exhibit impaired calcium handling with increasing pacing frequency, which correlated with impairment of both cell shortening and relengthening. (C) 2 000 Academic Press.