Cardiac adaptations from 4 weeks of intensity-controlled vigorous exercise are lost after a similar period of detraining

Abstract

Intensity-controlled (relative to VO2max) treadmill exercise training in adult rats results in the activation and ensuing differentiation of endogenous c-kitpos cardiac stem/progenitor cells (eCSCs) into newly formed cardiomyocytes and capillaries. Whether these training-induced adaptations persist following detraining is undetermined. Twelve male Wistar rats (~230 g) were exercised at 80-85% of their VO2maxfor 30 min day–1, 4 days week–1for 4 weeks (TR; n = 6), followed by 4 weeks of detraining (DTR; n = 6). Twelve untrained rats acted as controls (CTRL). Exercise training significantly enhanced VO2max(11.34 mL kg–1min–1) and wet heart weight (29%) above CTRL (P < 0.05). Echocardiography revealed that exercise training increased LV mass (~32%), posterior and septal wall thickness (~15%), ejection fraction and fractional shortening (~10%) compared to CTRL (P < 0.05). Cardiomyocyte diameter (17.9 ± 0.1 μm vs. 14.9 ± 0.6 μm), newly formed (BrdUpos/Ki67pos) cardiomyocytes (7.2 ± 1.3%/1.9 ± 0.7% vs. 0.2 ± 0.1%/0.1 _ 0.1%), total cardiomyocyte number (45.6 ± 0.6 9 106 vs. 42.5 ± 0.4 9 106), c-kitpos eCSC number (884 ± 112 per 106cardiomyocytes vs. 482 ± 132 per 106 cardiomyocytes), and capillary density (4123 ± 227 per mm2vs. 2117 ± 118 per mm2) were significantly greater in the LV of trained animals (P < 0.05) than CTRL. Detraining removed the stimulus for c-kitpos eCSC activation (640 ± 98 per 106 cardiomyocytes) and resultant cardiomyocyte hyperplasia (0.4 ± 0.3% BrdUpos/0.2 ± 0.2% Ki67poscardiomyocytes). Capillary density (3673 ± 374 per mm2) and total myocyte number (44.7 ± 0.5 × 106) remained elevated following detraining, but cardiomyocyte hypertrophy (15.0 ± 0.4 lm) was lost, resulting in a reduction of anatomical (wall thickness ~4%; LV mass ~10% and cardiac mass ~8%, above CTRL) and functional (EF & FS ~2% above CTRL) parameters gained through exercise training. These findings demonstrate that cardiac adaptations, produced by 4 weeks of intensity-controlled exercise training are lost after a similar period of detraining.