title: Investigation of the cardiac effects of pancuronium, rocuronium, vecuronium, and mivacurium on the isolated rat atrium.
abstract: BACKGROUND
  Pancuronium, vecuronium, rocuronium, and mivacurium are nondepolarizing neuromuscular blocking agents that affect the cardiovascular system with different potencies. Their cardiovascular effects are clinically significant in the anesthetic management of patients, particularly those undergoing cardiac surgery.
  
  
  OBJECTIVE
  We aimed to compare the cardiac effects of these compounds, such as heart rate and developed force, in one species under identical experimental conditions in isolated rat atria.
  
  
  METHODS
  The left or right atria of rats were removed and suspended in organ baths. Pancuronium, vecuronium, rocuronium, or mivacurium were added cumulatively (10(-9)-10(-5) M) in the presence and absence of the nonselective β-blocker propranolol (10(-8) M) and the noradrenaline reuptake inhibitor desipramine (10(-7) M), and heart rate changes were recorded in spontaneously beating right atria. Left atrial preparations were stimulated by electrical field stimulation using a bipolar platinum electrode, and the effects of cumulative concentrations of these nondepolarizing neuromuscular blocking agents on the developed force in the presence and absence of propranolol (10(-8) M) and desipramine (10(-7) M) were recorded.
  
  
  RESULTS
  Pancuronium increased heart rate in a dose-dependent manner compared with the control group (P < 0.027). Vecuronium, rocuronium, and mivacurium also increased heart rate in a dose-dependent manner, but the changes were not statistically significant. Although propranolol decreased the pancuronium heart rate effect (P < 0.05), it did not change the heart rate effects with vecuronium, rocuronium, or mivacurium. Desipramine did not change the heart rate effects of vecuronium, rocuronium, mivacurium, or pancuronium. All 4 drugs increased developed force in a dose-dependent manner; the increases were significant at 10(-5) M concentration for pancuronium and at 10(-6) and 10(-5) M concentrations for vecuronium, rocuronium, and mivacurium (P < 0.038). These increases in developed force were abolished with the addition of propranolol. Desipramine did not change the developed force effects of any of the 4 drugs.
  
  
  CONCLUSIONS
  The heart rate effect of pancuronium and developed force effects of pancuronium, vecuronium, rocuronium, and mivacurium may occur via direct stimulation of β receptors. Although our investigation was an in vitro study, the effects found may be important especially under pathologic conditions, such as hypertension, in which patients usually use β-blocking agents, which cause β receptor upregulation.
authors.affiliation: Department of Anesthesiology, Cumhuriyet University School of Medicine, Sivas, Turkey.
authors.forename: Sinan
authors.initials: S
authors.lastname: Gursoy
authors.affiliation: Department of Pharmacology, Cumhuriyet University School of Medicine, Sivas, Turkey.
authors.forename: Ihsan
authors.initials: I
authors.lastname: Bagcivan
authors.affiliation: Ministry of Health of Turkey, General Directorate of Pharmacy and Pharmaceuticals, Ankara, Turkey.
authors.forename: Nedim
authors.initials: N
authors.lastname: Durmus
authors.affiliation: Department of Anesthesiology, Cumhuriyet University School of Medicine, Sivas, Turkey.
authors.forename: Kenan
authors.initials: K
authors.lastname: Kaygusuz
authors.affiliation: Department of Anesthesiology, Cumhuriyet University School of Medicine, Sivas, Turkey.
authors.forename: Iclal Ozdemir
authors.initials: IO
authors.lastname: Kol
authors.affiliation: Department of Anesthesiology, Cumhuriyet University School of Medicine, Sivas, Turkey.
authors.forename: Cevdet
authors.initials: C
authors.lastname: Duger
authors.affiliation: Department of Pharmacology, Cumhuriyet University School of Medicine, Sivas, Turkey.
authors.forename: Sahin
authors.initials: S
authors.lastname: Yildirim
authors.affiliation: Department of Anesthesiology, Cumhuriyet University School of Medicine, Sivas, Turkey.
authors.forename: Caner
authors.initials: C
authors.lastname: Mimaroglu
keywords: atrium; mivacurium; neuromuscular blockers; pancuronium; rat; rocuronium; vecuronium