Mechanisms of improved arterial oxygenation after peripheral chemoreceptor stimulation during hypoxic exercise

Abstract

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.

Guidelines for the diagnosis and treatment of pulmonary hypertension

“…The definition of PH on exercise as a P pa .30 mmHg as assessed by RHC is not supported by published data and healthy individuals can reach much higher values [9,11]. Thus no definition for PH on exercise as assessed by RHC can be provided at the present time.…”

“…those variables that reflect RV function. Recommendations for the use of RHC in PAH patients are provided in table 11.…”

Pulmonary hypertension in left heart disease

“…However, the interpretation of these studies is complicated by the lack of a control group of age-and sexmatched normal individuals. In fact it is well known that normal individuals may also reach similar values of Ppcw (o20 mmHg) on supine exercise [59].…”

Effects of combined high-dose partial liquid ventilation and almitrine on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury

“…Almitrine is known as a peripheral chemoreceptor stimulant [30] increasing alveolar ventilation [31], but it has also been reported to affect pulmonary vessels directly [15,32]. This vasoactive effect seems to be responsible for its beneficial effect on pulmonary gas exchange in patients with acute respiratory failure.…”