Determination of maximal oxygen uptake with unsteady-state measurements.

Exercise on‐transition uncoupling of ventilatory, gas exchange and cardiac hemodynamic kinetics accompany pulmonary oxygen stores depletion to impact exercise intolerance in human heart failure

“…Observations taken from separate studies of healthy adults across the ageing spectrum as well as those with cardiac disease (not specific to HF) indeed suggest the exercise on‐transition balance between the availability, depletion and repletion of O 2stores plays an appreciable role in dynamic adjustments that occur between ventilation, gas exchange and cardiac haemodynamics . The effect of temporal dyssynchrony across ventilation, gas exchange and cardiac haemodynamics followed by dynamic O 2store availability and utilization is particularly important within the exercise on‐transition phase heading towards windows of highly O 2 ‐dependent metabolic demand .…”

“…The effect of temporal dyssynchrony across ventilation, gas exchange and cardiac haemodynamics followed by dynamic O 2store availability and utilization is particularly important within the exercise on‐transition phase heading towards windows of highly O 2 ‐dependent metabolic demand . Auchincloss et al provides original evidence to suggest the interdependence between the exercise on‐transition rate of responsiveness for E with respect to gas flow and metabolic load, the initial availability and immediate capacity to replenish O 2stores , and the rate of rise in E intersect to substantially dictate the trajectory of subsequent ventilatory demand as exercise persists. As an example of this, for HF patients in the present study, because of pronounced exercise on‐transition lag in kinetics for E compared with those for O 2 pulse and to a lesser extent O 2 and CO 2 , this temporal asymmetry necessitates excessive O 2store contribution to O 2 to the extent where even with transient hyperventilation, E cannot effectively facilitate O 2store repletion .…”

“…Auchincloss et al provides original evidence to suggest the interdependence between the exercise on‐transition rate of responsiveness for E with respect to gas flow and metabolic load, the initial availability and immediate capacity to replenish O 2stores , and the rate of rise in E intersect to substantially dictate the trajectory of subsequent ventilatory demand as exercise persists. As an example of this, for HF patients in the present study, because of pronounced exercise on‐transition lag in kinetics for E compared with those for O 2 pulse and to a lesser extent O 2 and CO 2 , this temporal asymmetry necessitates excessive O 2store contribution to O 2 to the extent where even with transient hyperventilation, E cannot effectively facilitate O 2store repletion . Thus, paired with a gross inability to replenish O 2stores despite ventilatory gain that is far in‐excess of metabolic demand, we hypothesize that HF tolerate O 2store “debt” by relying on a persistent rate‐mediated surge in E , whereby secondarily contributing to an inability to maintain equilibrium with CO 2 (ie, high E /CO 2 ratio and slope).…”

“…Lengthened O 2 kinetics demonstrated by HF also relate with integrative pathophysiology linked to features such as slowed response rates for adjustments in blood flow and oxidative phosphorylation relative to adenosine tri‐phosphate requirement . Separately, others report for adults without HF, those with delayed exercise on‐transition O 2 could also be expected to demonstrate asynchronous responsiveness across E , CO 2 and cardiac haemodynamics . Thus, while it is still unknown for human HF, an overall lack of confluence at the exercise on‐transition for aforementioned key physiological responses may be a precipitating factor for high and early recruitment of O 2 ‐independent metabolic contributions to total metabolic demand, narrowing of the predominant oxidative metabolic window of exercise and closely following exercise intolerance …”

“…With slowed E responsiveness relative to that for O 2 , CO 2 and cardiac haemodynamics at the exercise on‐transition, it has been proposed in those without HF that this may provoke rapid depletion of O 2stores and a lessened ability of this mechanism to contribute to subsequent increases in oxidative metabolic demand . The gross physiological uncoupling of O 2 transport features within the exercise on‐transition window may serve as a potent mechanism leading to ventilatory demand that is persistently exaggerated for a given workload domain …”