title: Esmolol infusion versus propranolol infusion: effects on heart rate and blood pressure in healthy volunteers.
abstract: Despite its widespread clinical use, the β1-adrenergic receptor antagonist esmolol hydrochloride is not commonly used in human physiology research, and the effective dose of esmolol (compared with the nonselective β-blocker propranolol) is unclear. In four separate studies we used cycle ergometry exercise and infusions of isoproterenol and epinephrine to test the heart rate (HR)-lowering effect of esmolol compared with propranolol and saline in healthy humans. Incohort 1, both esmolol (ΔHR 57 ± 6 beats/min) and propranolol (ΔHR 56 ± 7 beats/min) attenuated exercise tachycardia compared with saline (ΔHR 88 ± 17 beats/min). Incohort 2, we found that the HR response to exercise was similar at 5 min (ΔHR 57 ± 9 beats/min) and 60 min (ΔHR 55 ± 9 beats/min) after initiation of the esmolol maintenance infusion. Incohort 3, we confirmed that the HR-lowering effect of esmolol disappeared 45 min after termination of the maintenance infusion. Incohort 4, changes in femoral blood flow and hematological parameters in response to epinephrine infusion were not different between esmolol and saline infusion, indicating that our esmolol infusion paradigm does not block β2-receptors. Collectively, our data indicate that infusion of ~160 mg of esmolol (range 110-200 mg in the 5 min before exercise) acutely and selectively blocks β1-receptors in healthy humans. Additionally, β1-receptors remain blocked 60 min later if a maintenance infusion of ~0.2 mg·kg total body mass-1·min-1continues. The current data lay the foundation for future studies to evaluate β1- vs. β2-receptor control of the circulation in humans.NEW & NOTEWORTHYWe used cycle ergometry exercise and infusions of isoproterenol and epinephrine to test the heart rate-lowering effect of esmolol compared with propranolol and saline in healthy humans. Collectively, our data indicate that infusion of ~160 mg of esmolol (range 110-200 mg in the 5 min before exercise) acutely and selectively blocks β1-adrenergic receptors. These infusion parameters can be used in future experiments to evaluate β1- vs. β2-receptor control of the circulation in humans.
authors.affiliation: Penn State Heart and Vascular Institute, Penn State University College of Medicine, Hershey, Pennsylvania; mmuller1@hmc.psu.edu.|Master of Science in Anesthesia Program, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Matthew D
authors.identifier: http://orcid.org/0000-0002-7411-8816
authors.initials: MD
authors.lastname: Muller
authors.affiliation: Penn State Heart and Vascular Institute, Penn State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Tariq Ali
authors.initials: TA
authors.lastname: Ahmad
authors.affiliation: Penn State Heart and Vascular Institute, Penn State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Alvaro F
authors.initials: AF
authors.lastname: Vargas Pelaez
authors.affiliation: Department of Kinesiology, Noll Laboratory, The Pennsylvania State University, University Park, Pennsylvania.
authors.forename: David N
authors.initials: DN
authors.lastname: Proctor
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, Penn State University College of Medicine, Hershey, Pennsylvania; and.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Bonavia
authors.affiliation: Penn State Heart and Vascular Institute, Penn State University College of Medicine, Hershey, Pennsylvania.
authors.forename: J Carter
authors.initials: JC
authors.lastname: Luck
authors.affiliation: Penn State Heart and Vascular Institute, Penn State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Maman
authors.affiliation: Penn State Heart and Vascular Institute, Penn State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Ross
authors.affiliation: Penn State Heart and Vascular Institute, Penn State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Urs A
authors.initials: UA
authors.lastname: Leuenberger
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, Penn State University College of Medicine, Hershey, Pennsylvania; and.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: McQuillan
mesh_terms: D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology*; D005080:Exercise Test; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology*; D012016:Reference Values; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D011412:Propanolamines; D011433:Propranolol; C036604:esmolol
keywords: blood pressure; heart rate; sympathetic nervous system