Subendocardial Coronary Reserve as a Mechanism for the Preserved Cardiac Function in Rats vs Mice with Chronic Pressure Overload

Abstract

We compared the effects of chronic (4 wks) pressure overload induced by aortic banding in rats and mice. As expected, LV function, as assessed by LV ejection fraction (EF), measured echocardiographically, declined in the mouse model (from 72±0.3% to 61±1%, p<0.01) accompanied by increased LV systolic wall stress (102±5.4 vs. 58±1.8 dyn/cm2, p<0.01); the LV/aortic pressure gradient was 98±3mmHg. In the rat, the pressure gradient was greater (145±7mmHg, p<0.05), but LVEF actually increased (from 73±1% to 78±1%, p<0.05) and LV wall stress did not increase (68±5.6 dyn/cm2). Reduced coronary reserve is one mechanism responsible for the reduced LV function with LV overload and hypertrophy (H). Coronary reserve, the increase in coronary flow velocity with adenosine measured echocardiographically, was similar in sham rats and mice (2.22 vs 2.44), and was reduced, p<0.05, in LVH mice (1.76), but preserved in LVH rats (2.21). One potential mechanism for the preserved coronary reserve is angiogenesis. Capillary density, measured by the endothelial cell marker (isolectin), was similar in sham rats and mice, but higher, p<0.05, in rats than mice with LVH (497 vs 407 units/mm2). Thus, the rat model appears unique in tolerating an unusually severe pressure gradient without compromising LV function or LV wall stress, which may be attributed to the preservation of coronary reserve through enhanced angiogenesis.