Interindividual variability in the dose-specific effect of dopamine on carotid chemoreceptor sensitivity to hypoxia

Abstract

Human studies use varying levels of low-dose (1-4 μg·kg(-1)·min(-1)) dopamine to examine peripheral chemosensitivity, based on its known ability to blunt carotid body responsiveness to hypoxia. However, the effect of dopamine on the ventilatory responses to hypoxia is highly variable between individuals. Thus we sought to determine 1) the dose response relationship between dopamine and peripheral chemosensitivity as assessed by the ventilatory response to hypoxia in a cohort of healthy adults, and 2) potential confounding cardiovascular responses at variable low doses of dopamine. Young, healthy adults (n = 30, age = 32 ± 1, 24 male/6 female) were given intravenous (iv) saline and a range of iv dopamine doses (1-4 μg·kg(-1)·min(-1)) prior to and throughout five hypoxic ventilatory response (HVR) tests. Subjects initially received iv saline, and after each HVR the dopamine infusion rate was increased by 1 μg·kg(-1)·min(-1). Tidal volume, respiratory rate, heart rate, blood pressure, and oxygen saturation were continuously measured. Dopamine significantly reduced HVR at all doses (P < 0.05). When subjects were divided into high (n = 13) and low (n = 17) baseline chemosensitivity, dopamine infusion (when assessed by dose) reduced HVR in the high group only (P < 0.01), with no effect of dopamine on HVR in the low group (P > 0.05). Dopamine infusion also resulted in a reduction in blood pressure (3 μg·kg(-1)·min(-1)) and total peripheral resistance (1-4 μg·kg(-1)·min(-1)), driven primarily by subjects with low baseline chemosensitivity. In conclusion, we did not find a single dose of dopamine that elicited a nadir HVR in all subjects. Additionally, potential confounding cardiovascular responses occur with dopamine infusion, which may limit its usage.

Intact blood pressure, but not sympathetic, responsiveness to sympathoexcitatory stimuli in a patient with unilateral carotid body resection

“…; Limberg et al. ). Typical physiologic responses in anatomically intact humans would be increased sympathetic output (i.e., increased HR, BP, ventilatory rate, and increased MSNA) during stressors such as IHE/PEI, CPT, and LBNP.…”

“…Measures of HR variability (HRV), cardiac output (CO), and total peripheral resistance (TPR) were calculated using three lead electrocardiography, finger photoplethysmography, and off‐line analysis with custom software (WinCPRS, Version 1.163, Absolute Aliens Oy, Turku, Finland) (Limberg et al. ). Baroreflex sensitivity (BRS) was measured via trials of lower body negative pressure (LBNP, for simulation of venous pooling) (Somers et al.…”

“…During graded trials of increasing levels of hypoxia and stable normocapnia, the slope of the regression line between S p O 2 and minute ventilation (a measure of CB sensitivity to hypoxia, HVR) was measured as −0.23 L/min/% (healthy range: −0.19 to −0.93 L/min/% (Limberg et al. )). MSNA burst area was inversely correlated with S p O 2 ( r = −0.48).…”

Role of the carotid body chemoreceptors in glucose homeostasis and thermoregulation in humans

“…decreased CB chemosensitivity) during normothermic dopamine infusion along with the expected increase in ventilation (>2 L min −1 ) during the saline hyperthermia trial – highlighting the limits of using experimental low‐dose dopamine to attenuate CB activation (Limberg et al . ). Therefore, we separately analysed data from seven subjects that had a lower ventilatory response to hypoxia under normothermia during dopamine infusion and a >2 L min −1 increase in ventilation during hyperthermia with saline infusion.…”

“…One session was completed while a low dose of dopamine was infused to blunt CB activation (Limberg et al . ), and saline was infused during the other session. During the dopamine infusion, the cumulative plasma glucose response during exercise was ∼13% lower and a trend for an attenuated noradrenaline response was also observed.…”