title: Direct negative chronotropic action of desflurane on sinoatrial node pacemaker activity in the guinea pig heart.
abstract: BACKGROUND
  Desflurane inhalation is associated with sympathetic activation and concomitant increase in heart rate in humans and experimental animals. There is, however, little information concerning the direct effects of desflurane on electrical activity of sinoatrial node pacemaker cells that determines the intrinsic heart rate.
  
  
  METHODS
  Whole-cell patch-clamp experiments were conducted on guinea pig sinoatrial node pacemaker cells to record spontaneous action potentials and ionic currents contributing to sinoatrial node automaticity, namely, hyperpolarization-activated cation current (If), T-type and L-type Ca currents (ICa,T and ICa,L, respectively), Na/Ca exchange current (INCX), and rapidly and slowly activating delayed rectifier K currents (IKr and IKs, respectively). Electrocardiograms were recorded from ex vivo Langendorff-perfused hearts and in vivo hearts.
  
  
  RESULTS
  Desflurane at 6 and 12% decreased spontaneous firing rate of sinoatrial node action potentials by 15.9% (n = 11) and 27.6% (n = 10), respectively, which was associated with 20.4% and 42.5% reductions in diastolic depolarization rate, respectively. Desflurane inhibited If, ICa,T, ICa,L, INCX, and IKs but had little effect on IKr. The negative chronotropic action of desflurane was reasonably well reproduced in sinoatrial node computer model. Desflurane reduced the heart rate in Langendorff-perfused hearts. High concentration (12%) of desflurane inhalation was associated with transient tachycardia, which was totally abolished by pretreatment with the β-adrenergic blocker propranolol.
  
  
  CONCLUSIONS
  Desflurane has a direct negative chronotropic action on sinoatrial node pacemaking activity, which is mediated by its inhibitory action on multiple ionic currents. This direct inhibitory action of desflurane on sinoatrial node automaticity seems to be counteracted by sympathetic activation associated with desflurane inhalation in vivo.
authors: From the Department of Anesthesiology (A.K., Y.I., H.K., S.N.) and Department of Physiology (H.M.), Shiga University of Medical Science, Otsu, Shiga, Japan.
authors: Akiko
authors: A
authors: Kojima
authors: Yuki
authors: Y
authors: Ito
authors: Hirotoshi
authors: H
authors: Kitagawa
authors: Hiroshi
authors: H
authors: Matsuura
authors: Shuichi
authors: S
authors: Nosaka
mesh_terms: D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000077335:Desflurane; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D011897:Random Allocation; D012849:Sinoatrial Node / Q000187:drug effects* / Q000502:physiology
chemical_list: D018685:Anesthetics, Inhalation; D000077335:Desflurane; D007530:Isoflurane