title: Effects of acute systemic endothelin receptor blockade on cardiac electrophysiology in vivo.
abstract: BQ-123, a selective endothelin-A receptor antagonist, has been demonstrated to suppress arrhythmias. However, the role of physiologic levels of endogenous endothelin-1 (ET-1) with respect to electrophysiologic properties of the heart is unknown. BQ-123 (0.45, 0.9, 1.8, 3.6, 7.2, and 14.4 microg/kg/min; n = 10) or saline (control, n = 5) was administered IV for 15 minutes of continuous-rate infusion at incremental doses to anesthetized normal pigs. BQ-123 had no effect on PR and QT interval, QRS duration, intraatrial and AV nodal conduction time as well as the atrial, AV nodal, and ventricular effective refractory periods. As compared with baseline, BQ-123 at 7.2 and 14.4 microg/kg/min caused an increase in heart rate (99 +/- 17 versus 110 +/- 14 and 118 +/- 14 bpm, respectively; P < 0.05), shortened sinus node recovery time (818 +/- 165 versus 641 +/- 69 and 609 +/- 74 milliseconds, respectively; P < 0.05) and decreased mean arterial pressure at 14.4 microg/kg/min (95 +/- 18 versus 80 +/- 11 mm Hg; P < 0.05). We conclude that in the normal pig, physiologic levels of ET-1 have no effect on conduction properties of atrial, AV nodal, or Purkinje fibers. However, antagonism of ET-1 by BQ-123 unmasks the effect of ET-1 on maintenance of vasomotor tone, which in turn may affect heart rate and sinus node automaticity in the intact pig.
authors.affiliation: College of Veterinary Medicine, Cornell University, Ithaca, New York, USA. arg9@cornell.edu
authors.forename: Anna R M
authors.initials: AR
authors.lastname: Gelzer
authors.forename: Tim
authors.initials: T
authors.lastname: Attmann
authors.forename: Dirk
authors.initials: D
authors.lastname: Radicke
authors.forename: Daryl
authors.initials: D
authors.lastname: Nydam
authors.forename: Reto
authors.initials: R
authors.lastname: Candinas
authors.forename: Georg
authors.initials: G
authors.lastname: Lutter
mesh_terms: D000818:Animals; D016275:Atrial Function / Q000502:physiology; D001283:Atrioventricular Node / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002036:Bundle of His / Q000187:drug effects / Q000502:physiology; D002304:Cardiac Pacing, Artificial / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004558:Electric Stimulation / Q000379:methods; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac / Q000379:methods*; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000493:pharmacokinetics; D044022:Receptor, Endothelin A / Q000008:administration & dosage / Q000502:physiology*; D012849:Sinoatrial Node / Q000187:drug effects / Q000502:physiology; D013552:Swine; D013997:Time Factors; D016276:Ventricular Function; D017725:Ventricular Pressure / Q000187:drug effects / Q000502:physiology
chemical_list: D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; C072247:cyclo(Trp-Asp-Pro-Val-Leu)