Abstract
The human pulmonary vasculature constricts in response to hypercapnia and hypoxia, with important consequences for homeostasis and adaptation. One function of these responses is to direct blood flow away from poorly-ventilated regions of the lung. In humans it is not known whether the stimuli of hypercapnia and hypoxia constrict the pulmonary blood vessels independently of each other or whether they act synergistically, such that the combination of hypercapnia and hypoxia is more effective than the sum of the responses to each stimulus on its own. We independently controlled the alveolar partial pressures of carbon dioxide (Paco 2) and oxygen (Pao 2) to examine their possible interaction on human pulmonary vasoconstriction. Nine volunteers each experienced sixteen possible combinations of four levels of Paco 2 (+6, +1, −4 and −9 mmHg, relative to baseline) with four levels of Pao 2 (175, 100, 75 and 50 mmHg). During each of these sixteen protocols Doppler echocardiography was used to evaluate cardiac output and systolic tricuspid pressure gradient, an index of pulmonary vasoconstriction. The degree of constriction varied linearly with both Paco 2 and the calculated haemoglobin oxygen desaturation (1-So 2). Mixed effects modelling delivered coefficients defining the interdependence of cardiac output, systolic tricuspid pressure gradient, ventilation, Paco 2 and So 2. No interaction was observed in the effects on pulmonary vasoconstriction of carbon dioxide and oxygen (p>0.64). Direct effects of the alveolar gases on systolic tricuspid pressure gradient greatly exceeded indirect effects arising from concurrent changes in cardiac output.
Highlights
The human pulmonary vasculature constricts in response to both hypercapnia and hypoxia [1,2,3,4]
The luxury available in animal preparations of being able to impose a constant pulmonary flow, and using pulmonary artery pressure or pulmonary vascular resistance (PVR) as the index of vasoconstriction, has not been achieved in humans [22]. We address this problem by using mixed effects modelling to extract coefficients in direct and indirect pathways linking PACO2 and PAO2 with pulmonary artery pressure, and the relative contribution of each pathway
The middle panels show the ventilations and cardiac outputs achieved during the protocols and 1714 with hypercapnia (PETCO2 = baseline+6 mmHg) and hypoxia (PETO2 = 50 mmHg) using spontaneous hyperventilation; right panels: volunteer 1719 with hypocapnia (PETCO2 = baseline29 mmHg) and hyperoxia (PETO2 = 175 mmHg) using voluntarily controlled constant hyperventilation
Summary
The human pulmonary vasculature constricts in response to both hypercapnia and hypoxia [1,2,3,4]. An example is human exposure to high altitude, where the whole lung is exposed to coexisting hypoxia and hypocapnia [6], and the potentially harmful pressor effect of the alveolar hypoxia is obtunded by the dilatory effect of the alveolar hypocapnia. It is not known in what way a combination of the stimuli of hypercapnia and hypoxia affect the blood vessels in the human lung. Whether the effects of the stimuli are additive or synergistic, that is to say, whether variations in O2 could potentially enhance the response to CO2 or vice-versa
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