title: Anesthetics and automaticity in latent pacemaker fibers. IV. Effects of isoflurane and epinephrine or norepinephrine on automaticity of dominant and subsidiary atrial pacemakers in the canine heart.
abstract: BACKGROUND
  Anesthesia and surgery may be associated with atrioventricular junctional or ventricular rhythm disturbances. These may be caused by alteration of automaticity of primary and subsidiary pacemakers.
  
  
  METHODS
  The direct effects of isoflurane, alone or in combination with epinephrine (E) and norepinephrine (NE), as well as single effects of E and NE, were examined on automaticity of primary and subsidiary atrial pacemakers (SAP) using a perfused canine right atrial preparation (n = 29). Preparations were perfused with oxygenated Krebs' solution at a constant perfusion pressure of 87 mmHg and a temperature of 36.5 +/- 0.5 degrees C. Delivered concentrations of isoflurane of 1.4 and 2.8% corresponded to measured perfusate concentrations of 315 +/- 7 and 617 +/- 16 microM in experiments with E (n = 14), and 316 +/- 10 and 610 +/- 26 microM in experiments with NE (n = 15). Epinephrine or NE perfusate concentrations were 2 and 5 micrograms/l or 5 and 10 micrograms/l, respectively. To determine the site of earliest activation, extracellular recordings were made from the SA node region and distal sites (approximately 1, 2, and 3 cm) along the sulcus terminalis, the previously reported locations of SAP. Sites of earliest activation shifts from SA node to SAP were scored 1, 2, or 3 depending on the distance from the control pacemaker. The summed shift scores (magnitude score) were normalized by dividing by the total number of preparations for each experimental condition.
  
  
  RESULTS
  Exposure to isoflurane, NE, or E alone did not produce a significant increase in the incidence of pacemaker shifts or normalized pacemaker shift scores. Only the high dose of E significantly increased the incidence of pacemaker shifts and normalized shift scores. Dysrhythmogenic potential of E and NE tended to be greater after earlier exposure to isoflurane. Every combination of isoflurane with E or NE produced a significant increase in the incidence of pacemaker shifts and normalized shift scores.
  
  
  CONCLUSIONS
  It was concluded that isoflurane with E or NE acts synergistically to increase dysrhythmic potential in the arterial tissue.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
authors.forename: M
authors.initials: M
authors.lastname: Boban
authors.forename: J L
authors.initials: JL
authors.lastname: Atlee
authors.forename: M
authors.initials: M
authors.lastname: Vicenzi
authors.forename: J P
authors.initials: JP
authors.lastname: Kampine
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Bosnjak
mesh_terms: D000818:Animals; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D012849:Sinoatrial Node / Q000187:drug effects* / Q000502:physiology
chemical_list: D007530:Isoflurane; D009638:Norepinephrine; D004837:Epinephrine