Cardiac function in young and old Little mice

Abstract

We studied cardiac function in young and old, wild-type (WT), and longer-living Little mice using cardiac flow velocities, echocardiographic measurements, and left ventricular (LV) pressure (P) to determine if enhanced reserves were in part responsible for longevity in these mice. Resting/baseline cardiac function, as measured by velocities, LV dimensions, +dP/dt(max), and -dP/dt(max), was significantly lower in young Little mice versus young WT mice. Fractional shortening (FS) increased significantly, and neither +dP/dt(max) nor -dP/dt(max) declined with age in Little mice. In contrast, old WT mice had no change in FS but had significantly lower +dP/dt(max) and -dP/dt(max) versus young WT mice. Significant decreases were observed in the velocity indices of old Little mice versus old WT mice, but other parameters were unchanged. The magnitude of dobutamine stress response remained unchanged with age in Little mice, while that in WT mice decreased. These data suggest that while resting cardiac function in Little mice versus WT mice is lower at young age, it is relatively unaltered with aging. Additionally, cardiac function in response to stress was maintained with age in Little mice but not in their WT counterparts. Thus, some mouse models of increased longevity may not be associated with enhanced reserves.

Figure 1

Echocardiographic measurement of left ventricular (LV) dimensions (LV end-diastolic dimension [LVEDD] and LV end-systolic dimension [LVESD]) and percent fractional shortening (%FS) in young and old Little and wild-type (WT) mice.

Figure 2

Baseline and postdobutamine left ventricular pressure parameters in 8 young wild-type (WT) (a) and 7 young Little mice (b) (^¶p < .01, ^#p < .05 postdobutamine vs baseline). The heart rates at (WT vs Little) were 392 ± 18 versus 363 ± 32 beats/min at baseline and 541 ± 9 versus 535 ± 10 beats/min postdobutamine.

Figure 3

Baseline and postdobutamine left ventricular pressure parameters in 7 old wild-type (WT) (a) and 6 old Little mice (b) (^¶p < .01, ^#p < .05 postdobutamine vs baseline). The heart rates at (WT vs Little) were 392 ± 8 versus 385 ± 6 beats/min at baseline and 559 ± 25 versus 515 ± 25 beats/min postdobutamine.

Figure 4

Plot of hypothetical curves concerning cardiac function in mice with different levels of insulin-like growth factor 1 (IGF-I): SIS2 mouse (high), wild-type (WT) mouse (normal), and Little mouse (low).