Prior heavy exercise elevates pyruvate dehydrogenase activity and muscle oxygenation and speeds O₂uptake kinetics during moderate exercise in older adults

Abstract

(V O2p) kinetics during the transition to moderate-intensity exercise is slowed in older compared with younger adults; however, this response is faster following a prior bout of heavy-intensity exercise. We have examined V O2p kinetics, pyruvate dehydrogenase (PDH) activation, muscle metabolite contents, and muscle deoxygenation in older adults [n ϭ 6; 70 Ϯ 5 (67-74) yr] during moderate-intensity exercise (Mod 1) and during moderate-intensity exercise preceded by heavy-intensity warm-up exercise (Mod2). The phase 2 V O2p time constant (V O2p) was reduced (P Ͻ 0.05) in Mod2 (29 Ϯ 5 s) compared with Mod1 (39 Ϯ 14 s). PDH activity was elevated (P Ͻ 0.05) at baseline prior to Mod2 (2.1 Ϯ 0.6 vs. 1.2 Ϯ 0.3 mmol acetyl-CoA ⅐ min Ϫ1 ⅐ kg wet wt Ϫ1 ), and the delay in attaining end-exercise activity was abolished. Phosphocreatine breakdown during exercise was reduced (P Ͻ 0.05) at both 30 s and 6 min in Mod2 compared with Mod1. Near-infrared spectroscopyderived indices of muscle oxygenation were elevated both prior to and throughout Mod2, while muscle deoxygenation kinetics were not different between exercise bouts consistent with elevated perfusion and O2 availability. These results suggest that in older adults, faster V O2p kinetics following prior heavy-intensity exercise are likely a result of prior activation of mitochondrial enzyme activity in combination with elevated muscle perfusion and O2 availability. V O2 kinetics; ageing; pyruvate dehydrogenase; phosphocreatine DURING THE TRANSITION TO moderate-intensity exercise there is a delay in the full activation of mitochondrial oxidative phosphorylation, as estimated by pulmonary O 2 uptake (V O 2p ) kinetics (2, 21, 38), such that it can take several minutes before a new steady-state in aerobic ATP production meets ATP demand (55). It has been suggested that this delay is a result of either a slowed activation of oxidative enzymes and provision of substrates other than O 2 to the mitochondrial tricarboxylic acid (TCA) cycle and electron transport chain (ETC) (e.g., acetyl-CoA; NADH) (20,42), an inadequate supply of O 2 during the transition to exercise (33), or the interaction between these two (22,54). In older compared with young adults, V O 2p kinetics, reflecting the adaptation of muscle O 2 utilization, are slowed during the transition to moderate-and heavyintensity exercise (1, 5, 9, 11). Whether this slower response in older adults is a result of an increased sluggishness in activating muscle enzymes and providing oxidative substrate (occasionally referred to as metabolic inertia), an impaired O 2 delivery, or both has not been established.Recently, we demonstrated that the activation of the mitochondrial enzyme pyruvate dehydrogenase (PDH) was attenuated during the transition to moderate-intensity exercise in older compared with young adults (23). To our knowledge this is the first direct demonstration, in older adults, that the activation of a rate-limiting oxidative enzyme is impaired during the transition to exercise. These data suggest a potential rol...

The intramuscular contribution to the slow oxygen uptake kinetics during exercise in chronic heart failure is related to the severity of the condition

“…The correlation between resting muscle oxygenation and V O 2 kinetics in the present study (Fig. 4), however, suggests that the flux control for V O 2 kinetics may be more sensitive to O 2 delivery in CHF patients than in the healthy population (20,21).…”

“…In healthy young and elderly individuals, prior exercise has had varied success in speeding V O 2 kinetics. Some studies have shown a benefit, but only when the warm-up exercise exceeded the LT (11,20,21). Only one previous study (in heart transplant recipients) has reported a speeding of V O 2 kinetics following prior moderate exercise (38).…”

“…Any increase in O 2 availability afforded by the prior exercise intervention, however, is accompanied by the activation of intramuscular enzymes involved in oxidative metabolism (11,16,20,21,49). Healthy volunteers with relatively slow V O 2 kinetics can speed V O 2 by a supra-LT warm-up, which increases the activity of pyruvate dehydrogenase and reduces demands for breakdown of phosphocreatine (21,46).…”

“…This overshoot in deoxygenation has also been reported in patients with type 2 diabetes (5), pulmonary arterial hypertension (3), and chronic obstructive pulmonary disease (50), as well as in young men following prolonged bed rest (40). Whether this overshoot in muscle deoxygenation presents a limitation to O 2 diffusion between the capillary and mitochondrion or whether it contributes to slowing V O 2 kinetics in CHF is unclear.Previous studies in active healthy young and elderly participants have shown that V O 2 kinetics can be speeded following a bout of prior (or warm-up) exercise in concert with increased microvascular oxygenation and activation of intracellular enzymes such as pyruvate dehydrogenase (20,21). This warm-up intervention, therefore, has the potential to reveal the locus of a "kinetic deficit" in O 2 delivery and/or utilization in CHF: an increase in O 2 delivery relative to muscle O 2 utilization after warm-up would slow microvascular deoxygenation, whereas speeding the intramuscular metabolic control signaling relative…”

“…Previous studies in active healthy young and elderly participants have shown that V O 2 kinetics can be speeded following a bout of prior (or warm-up) exercise in concert with increased microvascular oxygenation and activation of intracellular enzymes such as pyruvate dehydrogenase (20,21). This warm-up intervention, therefore, has the potential to reveal the locus of a "kinetic deficit" in O 2 delivery and/or utilization in CHF: an increase in O 2 delivery relative to muscle O 2 utilization after warm-up would slow microvascular deoxygenation, whereas speeding the intramuscular metabolic control signaling relative to O 2 delivery would speed microvascular deoxygenation kinetics.…”