title: 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.
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Limberg
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota; and Department of Exercise and Nutrition Sciences, University at Buffalo, Buffalo, New York.
authors.forename: Blair D
authors.initials: BD
authors.lastname: Johnson
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Walter W
authors.initials: WW
authors.lastname: Holbein
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Sushant M
authors.initials: SM
authors.lastname: Ranadive
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Mozer
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota; and joyner.michael@mayo.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Joyner
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002344:Carotid Body / Q000187:drug effects* / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000627:therapeutic use*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism; D012119:Respiration / Q000187:drug effects; D056152:Respiratory Rate / Q000187:drug effects; D013990:Tidal Volume / Q000187:drug effects; D055815:Young Adult
chemical_list: D010100:Oxygen; D004298:Dopamine
keywords: chemoreflex; hypoxic ventilatory response; peripheral chemoreceptors