Carvedilol and Exercise Combination Therapy Improves Systolic but not Diastolic Function and Reduces Plasma Osteopontin in Col4a3-/- Mice

Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00535.2020. Online ahead of print.ABSTRACTThere are currently no FDA-approved treatments for heart failure with preserved ejection fraction (HFpEF). Here we compared the effects of exercise with and without α/β-adrenergic blockade with carvedilol in Col4a3-/- Alport mice, a model of the Phenogroup 3 subclass of HFpEF with underlying renal dysfunction. Alport mice were assigned to the following groups: no treatment control (n=29), carvedilol (n=11), voluntary exercise (n=9), combination carvedilol and exercise (n=8). Cardiac function was assessed by echocardiography after 4-week treatments. Running activity of Alport mice was similar to wild types at 1-month of age, but markedly reduced at 2 months (1.3±0.40 vs. 4.5±1.02 km/day, p<0.05). There was a non-significant trend for increased running activity at 2 months by carvedilol in the combination treatment group. Combination treatments conferred increased body weight of Col4a3-/- mice (22.0±1.18 vs. 17.8±0.29 g in untreated mice, p<0.01), suggesting improved physiology, and heart rates declined by similar increments in all carvedilol-treatment groups. The combination treatment improved systolic parameters; stroke volume (30.5±1.99 vs. 17.8±0.77 μL, p<0.0001) as well as ejection fraction and global longitudinal strain compared with controls. Myocardial Performance Index was normalized by all interventions (p<0.0001). Elevated osteopontin pla...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Source Type: research