title: 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-kit(pos) 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 VO2max for 30 min day(-1), 4 days week(-1) for 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(-1) min(-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 (BrdU(pos)/Ki67(pos)) 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 × 10(6) vs. 42.5 ± 0.4 × 10(6)), c-kit(pos) eCSC number (884 ± 112 per 10(6) cardiomyocytes vs. 482 ± 132 per 10(6) cardiomyocytes), and capillary density (4123 ± 227 per mm(2) vs. 2117 ± 118 per mm(2)) were significantly greater in the LV of trained animals (P < 0.05) than CTRL. Detraining removed the stimulus for c-kit(pos) eCSC activation (640 ± 98 per 10(6) cardiomyocytes) and resultant cardiomyocyte hyperplasia (0.4 ± 0.3% BrdU(pos)/0.2 ± 0.2% Ki67(pos) cardiomyocytes). Capillary density (3673 ± 374 per mm(2)) and total myocyte number (44.7 ± 0.5 × 10(6)) remained elevated following detraining, but cardiomyocyte hypertrophy (15.0 ± 0.4 μm) 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.
authors.affiliation: Stem Cell and Regenerative Biology Unit (BioStem), Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, L3 3AF, UK.
authors.forename: Cheryl D
authors.initials: CD
authors.lastname: Waring
authors.affiliation: Stem Cell and Regenerative Biology Unit (BioStem), Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, L3 3AF, UK Centre of Human & Aerospace Physiological Sciences and Centre for Stem Cells & Regenerative Medicine, Faculty of Medicine & Life Sciences, King's College London, London, SE1 1UL, UK.
authors.forename: Beverley J
authors.initials: BJ
authors.lastname: Henning
authors.affiliation: Centre of Human & Aerospace Physiological Sciences and Centre for Stem Cells & Regenerative Medicine, Faculty of Medicine & Life Sciences, King's College London, London, SE1 1UL, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Smith
authors.affiliation: Centre of Human & Aerospace Physiological Sciences and Centre for Stem Cells & Regenerative Medicine, Faculty of Medicine & Life Sciences, King's College London, London, SE1 1UL, UK.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Nadal-Ginard
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, 88100, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Torella
authors.affiliation: Centre of Human & Aerospace Physiological Sciences and Centre for Stem Cells & Regenerative Medicine, Faculty of Medicine & Life Sciences, King's College London, London, SE1 1UL, UK Laboratory of Molecular and Cellular Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, 88100, Italy.
authors.forename: Georgina M
authors.initials: GM
authors.lastname: Ellison
keywords: Cardiac stem/progenitor cells; detraining; physiological remodeling