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Simultaneous assessment of central and peripheral chemoreflex regulation of muscle sympathetic nerve activity and ventilation in healthy young men
Author(s) -
Keir Daniel A.,
Duffin James,
Millar Philip J.,
Floras John S.
Publication year - 2019
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp277691
Subject(s) - central chemoreceptors , peripheral chemoreceptors , chemoreceptor , hypercapnia , hyperoxia , reflex , hypoxia (environmental) , medicine , peripheral , anesthesia , stimulation , respiratory system , lung , chemistry , receptor , organic chemistry , oxygen
Key points Central chemoreceptor stimulation, by hypercapnia (acidosis), and peripheral, by hypoxia plus hypercapnia, evoke reflex increases in ventilation and sympathetic outflow. The assumption that central or peripheral chemoreceptor‐mediated sympathetic activation elicited when P C O 2increases parallels concurrent ventilatory responses is unproven. Applying a modified rebreathing protocol that equilibrates central and peripheral chemoreceptor P C O 2whilst clamping O 2 tension at either hypoxic or hyperoxic concentrations, the independent ventilatory and muscle sympathetic stimulus–response properties of the central and peripheral chemoreflexes were quantified and compared in young men. The novel findings were that ventilatory and sympathetic responses to central and peripheral chemoreflex stimulation are initiated at similar P C O 2recruitment thresholds but individual specific sympathetic responsiveness cannot be predicted from the ventilatory sensitivities of either chemoreceptor reflex. Such findings in young men, if replicated in heart failure or hypertension, should temper present enthusiasm for trials targeting the peripheral chemoreflex based solely on ventilatory responsiveness to non‐specific chemoreceptor stimulation.Abstract In humans, stimulation of peripheral or central chemoreceptor reflexes is assumed to evoke equivalent ventilatory and sympathetic responses. We evaluated whether central or peripheral chemoreceptor‐mediated sympathetic activation elicited by increases in CO 2 tension ( P C O 2) parallels concurrent ventilatory responses. Twelve healthy young men performed a modified rebreathing protocol designed to equilibrate central and peripheral chemoreceptor P C O 2tensions with end‐tidal P C O 2( P ETC O 2) at two isoxic end‐tidal P O 2( P ET O 2) such that central responses can be segregated, by hyperoxia, from the net response (hypoxia minus hyperoxia). Ventilation and muscle sympathetic nerve activity (MSNA) were recorded continuously during rebreathing at isoxic P ET O 2of 150 and 50 mmHg. During rebreathing, the P ETC O 2values at which ventilation (L min −1 ) and total MSNA (units) began to rise were identified ( P ETC O 2recruitment thresholds) and their slopes above the recruitment threshold were determined (sensitivity). The central chemoreflex recruitment threshold for ventilation (46 ± 3 mmHg) and MSNA (45 ± 4 mmHg) did not differ ( P = 0.55) and slopes were 2.3 ± 0.9 L min −1 mmHg −1 and 2.1 ± 1.5 units mmHg −1 , respectively. The peripheral chemoreflex recruitment thresholds, at 41 ± 3 mmHg for both ventilation and MSNA were lower ( P < 0.05) compared to the central chemoreflex recruitment thresholds. Peripheral chemoreflex sensitivity was 1.7 ± 0.1 L min −1 mmHg −1 for ventilation and 2.9 ± 2.6 units mmHg −1 for MSNA. There was no relationship between the ventilatory and MSNA sensitivity for either the central ( r 2 = 0.01, P = 0.76) or peripheral ( r 2 = 0.01, P = 0.73) chemoreflex. In healthy young men, ventilatory and sympathetic responses to central and peripheral chemoreceptor reflex stimulation are initiated at similar P ETC O 2recruitment thresholds but individual ventilatory responsiveness does not predict sympathetic sensitivities of either chemoreflex.