title: Transmural heterogeneity of ventricular repolarization under baseline and long QT conditions in the canine heart in vivo: torsades de pointes develops with halothane but not pentobarbital anesthesia.
abstract: BACKGROUND
  In vitro studies have provided evidence for the existence of M cells. The present study examines the contribution of the M cell to transmural dispersion of repolarization (TDR) and to the development of torsades de pointes (TdP) in the canine heart in vivo in animals anesthetized with either pentobarbital or halothane.
  
  
  RESULTS
  Monophasic action potentials (MAPs) were recorded from 4 to 7 transmural sites, before and after d-sotalol. Cells displaying the longest MAP duration (MAPD) generally were localized to the deep subendocardium to mid-myocardium (M region) in the anterior wall of the left ventricle. d-Sotalol preferentially prolonged the MAPD of the M region, increasing TDR significantly more (P < 0.05) in animals anesthetized with halothane (31+/-5 to 88+/-17 msec) than in those receiving pentobarbital (24+/-9 to 53+/-7 msec; basic cycle length 1,500 msec). In halothane-anesthetized dogs, a remarkable transient increase in M cell MAPD followed interpolation of one or more extrasystole(s), leading to a transient increase in TDR and TdP. TdP was never observed with pentobarbital anesthesia.
  
  
  CONCLUSIONS
  Our results demonstrate that transmural heterogeneity of repolarization is amplified under acquired long QT conditions and that the increase in TDR underlies the development of TdP in halothane- but not pentobarbital-anesthetized dogs. The data support an important contribution of M cells to TDR and to the development of TdP in the canine heart in vivo. Our data also highlight the importance of acceleration-induced prolongation of MAPD (a phenomena observed principally in M cells) in the development of TdP.
authors.affiliation: Service de Pharmacologie, Faculté de Médecine Saint-Antoine, Université Pierre et Marie Curie, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Weissenburger
authors.forename: V V
authors.initials: VV
authors.lastname: Nesterenko
authors.forename: C
authors.initials: C
authors.lastname: Antzelevitch
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000768:Anesthesia, General / Q000009:adverse effects*; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D004195:Disease Models, Animal; D004285:Dogs; D004347:Drug Interactions; D004562:Electrocardiography; D005260:Female; D006221:Halothane / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008133:Long QT Syndrome / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010424:Pentobarbital / Q000494:pharmacology*; D013015:Sotalol / Q000627:therapeutic use; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D018685:Anesthetics, Inhalation; D000889:Anti-Arrhythmia Agents; D006993:Hypnotics and Sedatives; D013015:Sotalol; D010424:Pentobarbital; D006221:Halothane