Cardiac Function in Dwarf Mice

Abstract

Dwarf mice (Growth Hormone Releasing Hormone Receptor Null) live about 30% longer than wild type (WT) mice. We hypothesized that higher cardiac reserve in dwarf mice may contribute to their longer life span. We measured LV pressure at baseline and after the administration of dobutamine in 4 dwarf and 5 WT mice. The right carotid artery of the mouse was cannulated with a RADI Pressure Wire catheter and advanced via aorta into left ventricle. Baseline systolic and diastolic pressures (mmHg) were obtained from aortic pressure signals. Maximum ±dP/dt (mmHg/s) and tau (ms; time constant of −dP/dt) were calculated from the LV pressure signals. Data are mean ±SEM. The body weights (g) of the dwarf mice were significantly lower (13.1±0.8 vs. 23.1±0.4, p<0.01) with no differences in the heart rate (363±43 vs. 370±28 bpm), systolic pressure (99±6 vs. 109±9), and diastolic pressure (75±6 vs. 75±7). Baseline +dP/dtmax and −dP/dtmax were significantly lower in the dwarf mice, (4630±555 vs. 7333±628, p<0.02) and (−4599±549 vs. −7329±656, p<0.02), respectively, but tau showed greater variability (6.7±1.6 vs. 5.3±0.7). Post-dobutamine changes (as % of baseline) showed no differences between dwarf and WT mice for tau (53±6% vs. 51±7%) and +dP/dtmax (182±17% vs. 189±25%). However, post-dobutamine changes in −dP/dtmax were larger in dwarf mice (158±14% vs. 119±9%, p=0.05). These data show that the dwarf mice have impaired cardiac function at baseline compared to their WT counterparts, but have no increase in ionotropic (contractile) reserve than the WT animals. Our data are less clear for lusitropic (relaxation) reserve. We conclude that the extended longevity of the dwarf mice is not due to augmented cardiac reserves in youth.