Impaired Cell Shortening and Relengthening with Increased Pacing Frequency are Intrinsic to the Senescent Mouse Cardiomyocyte
Key result
Senescent mouse cardiomyocytes exhibit impaired calcium handling and blunted cell shortening and relengthening with increasing pacing frequency compared to adult myocytes.
Population
Freshly dissociated left ventricular myocytes isolated from young adult and senescent mouse hearts
Comparison
Pacing from 2 to 9 Hz at 37 degrees C vs Young adult mouse myocytes compared to senescent…
Design
Preclinical
Authors
Discussion
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Implication
Reveals intrinsic impairments in senescent cardiomyocyte function; leaves open translation to human cardiac aging or HFpEF.
Key Points
- To determine whether altered intracellular calcium regulation is directly responsible for impaired cell shortening and delayed relengthening in senescent cardiomyocytes during increased pacing frequency.
- Dissociated left ventricular myocytes from young adult and senescent mouse hearts.
- Electrically paced isolated myocytes from 2 to 9 Hz at 37 °C while simultaneously assessing cell shortening with video edge-detection and intracellular calcium dynamics via fura-2 fluorescence.
- Adult myocytes exhibited progressive increases in percent cell shortening (P < 0.01) and intracellular calcium transient amplitude (P < 0.05) with rising pacing frequency, whereas senescent myocytes showed no frequency-dependent increase in either parameter.
- Accelerated pacing elicited significantly steeper reductions in the time constants of relengthening and calcium transient decay in adult myocytes compared with senescent myocytes (P < 0.05).
Structured PICO
P
Population
Freshly dissociated left ventricular myocytes isolated from young adult and senescent mouse hearts.
E
Exposure
Pacing from 2 to 9 Hz at 37 degrees C
C
Comparator
Young adult mouse myocytes compared to senescent mouse myocytes
O
Outcome
Cell shortening and [Ca(2+)](i) transient amplitudesurrogate
Main Result
p-value: p=<0.01
Senescent mouse cardiomyocytes exhibit intrinsic impairments in calcium handling and contractility in response to increased pacing frequency compared to young adult cardiomyocytes.
Cite This Study
Lim et al. (2000) studied Senescence in mouse cardiomyocytes. Increased pacing frequency vs. Adult mouse myocytes was evaluated on Cell shortening and intracellular calcium transient amplitude and decay (p=<0.01). Senescent mouse cardiomyocytes exhibit impaired calcium handling and blunted cell shortening and relengthening with increasing pacing frequency compared to adult myocytes.