Mechanisms of improved arterial oxygenation after peripheral chemoreceptor stimulation during hypoxic exercise.
Almitrine, a peripheral chemoreceptor agonist, has been reported to increase arterial O2 saturation (SaO2) without changing minute ventilation (VE) during hypoxic exercise (Giesbrecht et al. J. Appl. Physiol. 70: 1770-1774, 1991). To explain this finding, we studied pulmonary hemodynamics (right heart catheterization) and gas exchange (multiple inert gas elimination technique) in six healthy volunteers at rest and during heavy exercise in normobaric normoxia (fractional concentration of O2 in inspired air 0.21) or hypoxia (fractional concentration of O2 in inspired air 0.125), before and after 75 mg of almitrine taken orally. During normoxic exercise, at a mean O2 uptake (VO2) of 4.0 l/min, almitrine increased arterial PO2 (PaO2) (P < 0.05), SaO2 (P < 0.01), and VE (P < 0.05) and decreased arterial PCO2 (P < 0.01), without affecting pulmonary hemodynamics or ventilation-perfusion distributions. During hypoxic exercise, at a mean VO2 of 3.0 l/min, almitrine increased SaO2 (P < 0.01) and VE (P < 0.01) and decreased arterial PCO2 (P < 0.05), with no effect on PaO2 or on ventilation-perfusion distributions and with a slight pulmonary vasoconstriction (P < 0.01). Almitrine during hypoxia did not affect cardiac output or calculated O2 diffusing capacity, but it did increase the slope of the VE/VO2 relationship (P < 0.01). We conclude that during hypoxic exercise, a pharmacological stimulation of the peripheral chemoreceptors improves SaO2 but not PaO2 by means of increased ventilation and an associated leftward shift of the oxyhemoglobin dissociation curve.
Naeije
R
R
Laboratory of Cardiovascular and Respiratory Physiology, Erasme University Hospital, Brussels, Belgium.
Mélot
C
C
Niset
G
G
Delcroix
M
M
Wagner
P D
PD
D000328:Adult; D015765:Almitrine / Q000494:pharmacology; D001158:Arteries; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000503:physiopathology*; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D008297:Male; D010100:Oxygen / Q000097:blood*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D011659:Pulmonary Gas Exchange / Q000187:drug effects / Q000502:physiology; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology
D015765:Almitrine; D010100:Oxygen