Aerobic fitness is associated with cardiomyocyte contractile capacity and endothelial function in exercise training and detraining

Background - Physical fitness and level of regular exercise are closely related to cardiovascular health. A regimen of regular intensity-controlled treadmill exercise was implemented and withdrawn to identify cellular mechanisms associated with exercise capacity and maximal oxygen uptake ((V) over dot O(2)max). Methods and Results - Time-dependent associations between cardiomyocyte dimensions, contractile capacity, and (V) over dot O(2)max were assessed in adult rats after high-level intensity-controlled treadmill running for 2, 4, 8, and 13 weeks and detraining for 2 and 4 weeks. With training, cardiomyocyte length, relaxation, shortening, Ca2+ decay, and estimated cell volume correlated with increased (V) over dot O(2)max ( r = 0.92, - 0.92, 0.88, - 0.84, 0.73; P < 0.01). Multiple regression analysis identified cell length, relaxation, and Ca2+ decay as the main explanatory variables for (V) over dot O(2)max (R-2 = 0.87, P < 0.02). When training stopped, exercise-gained (V) over dot O(2)max decreased 50% within 2 weeks and stabilized at 5% above sedentary controls after 4 weeks. Cardiomyocyte size regressed in parallel with (V) over dot O(2)max and remained (9%) above sedentary after 4 weeks, whereas cardiomyocyte shortening, contraction/relaxation- and Ca2+-transient time courses, and endothelium-dependent vasorelaxation regressed completely within 2 to 4 weeks of detraining. Cardiomyocyte length, estimated cell volume, width, shortening, and Ca2+ decay and endothelium-dependent arterial relaxation all correlated with (V) over dot O(2)max ( r = 0.85, 0.84, 0.75, 0.63, - 0.54, - 0.37; P < 0.01). Multiple regression identified cardiomyocyte length and vasorelaxation as the main determinants for regressed (V) over dot O(2)max during detraining (R-2 = 0.76, P = 0.02). Conclusions - Cardiovascular adaptation to regular exercise is highly dynamic. On detraining, most of the exercise-gained aerobic fitness acquired over 2 to 3 months is lost within 2 to 4 weeks. The close association between cardiomyocyte dimensions, contractile capacity, arterial relaxation, and aerobic fitness suggests cellular mechanisms underlying these changes.