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.

Keywords: chemoreflex; hypoxic ventilatory response; peripheral chemoreceptors.

Fig. 1.

Study Timeline. Subjects completed five infusion conditions over the course of 2.5 h. Each infusion condition consisted of 15 min of normoxic breathing with steady-state measurements completed during the last 5 min. After completion of steady-state measurements, peripheral chemosensitivity was assessed via four hypoxic challenges. After completion of the final hypoxic challenge, the next infusion condition commenced.

Fig. 2.

Effect of dopamine dose on the hypoxic ventilatory response (HVR), reported relative to responses during saline infusion (saline = 100%). High HVR (n = 13), low HVR (n = 17). Intravenous dopamine infusion resulted in a significant reduction in the HVR at each dopamine dose in subjects with high baseline chemosensitivity (black bars, P < 0.01). In contrast, those subjects exhibiting low baseline chemosensitivity showed no main effect of dopamine on the HVR (white bars, P = 0.20). Data are presented as means ± SE. DA, dopamine; number = dose in μg·kg⁻¹·min⁻¹. *P < 0.05 vs. saline.

Fig. 3.

Variability in the effect of dopamine dose on the HVR. HVR data are presented relative to responses during saline infusion (saline = 100%). Values >100% indicate an increase in HVR with dopamine infusion at a given dose: 1 μg·kg⁻¹·min⁻¹ (A) 2 μg·kg⁻¹·min⁻¹ (B), 3 μg·kg⁻¹·min⁻¹ (C), and 4 μg·kg⁻¹·min⁻¹ (D). Values <100% indicate a decrease in HVR with dopamine infusion. Horizontal dashed lines represent baseline HVR (100%), and vertical dashed lines separate subjects into those with high and low baseline chemosensitivity (n = 30 total).

Fig. 4.

Distribution of dopamine doses that elicited a nadir HVR, by percent of subjects studied. High HVR (n = 13), low HVR (n = 17). The dose of dopamine (1–4 μg·kg⁻¹·min⁻¹) that elicited a nadir HVR (with a <10% change in blood pressure) was determined for each subject. A: these results illustrate there is no uniform dose that is sufficient to cause a maximum reduction in the HVR in all subjects. Further, subjects with low baseline chemosensitivity (white bars) appear to require a relatively lower dose than those subjects with high baseline chemosensitivity (black bars). B: a consistent reduction (∼50%) in the HVR can be achieved with low-dose dopamine if the selected dose is allowed to vary. Data are presented as means ± SE.

Fig. 5.

Effect of dopamine dose on steady-state hemodynamics, reported relative to responses during saline infusion (saline = 100%). High HVR (n = 13), low HVR (n = 17). A: a significant reduction in blood pressure was observed in subjects with low baseline chemosensitivity during intravenous dopamine infusion (3 μg·kg⁻¹·min⁻¹) (white bars, P < 0.01). No changes in blood pressure were observed in subjects with high baseline chemosensitivity (black bars, P = 0.59). B: subjects with low baseline chemosensitivity exhibited a significant decrease in total peripheral resistance at each dose of dopamine (P < 0.01) which was not observed in subjects with high baseline chemosensitivity (P = 0.51). *P < 0.05 vs. saline; †P < 0.05 vs. 1 μg·kg⁻¹·min⁻¹. Data are presented as means ± SE.