Exercise capacity and cardiac hemodynamic response in female ApoE/LDLR−/− mice: a paradox of preserved V’O2max and exercise capacity despite coronary atherosclerosis

We assessed exercise performance, coronary blood flow and cardiac reserve of female ApoE/LDLR −/− mice with advanced atherosclerosis compared with age-matched, wild-type C57BL6/J mice. Exercise capacity was assessed as whole body maximal oxygen consumption (V’O 2max ), maximum running velocity (v max ) and maximum distance (DIST max ) during treadmill exercise. Cardiac systolic and diastolic function in basal conditions and in response to dobutamine (mimicking exercise-induced cardiac stress) were assessed by Magnetic Resonance Imaging (MRI) in vivo . Function of coronary circulation was assessed in isolated perfused hearts. In female ApoE/LDLR −/− mice V’O 2max , v max and DIST max were not impaired as compared with C57BL6/J mice. Cardiac function at rest and systolic and diastolic cardiac reserve were also preserved in female ApoE/LDLR −/− mice as evidenced by preserved fractional area change and similar fall in systolic and end diastolic area after dobutamine. Moreover, endothelium-dependent responses of coronary circulation induced by bradykinin (Bk) and acetylcholine (ACh) were preserved, while endothelium-independent responses induced by NO-donors were augmented in female ApoE/LDLR −/− mice. Basal COX-2-dependent production of 6-keto-PGF 1α was increased. Concluding, we suggest that robust compensatory mechanisms in coronary circulation involving PGI 2 - and NO-pathways may efficiently counterbalance coronary atherosclerosis-induced impairment in V’O 2max and exercise capacity.