title: Effect of volatile anesthetics on the force-frequency relation in human ventricular myocardium: the role of the sarcoplasmic reticulum calcium-release channel.
abstract: BACKGROUND
  In human ventricular myocardium, contractile force increases at higher stimulation frequencies (positive force-frequency relation). In failing hearts, the force-frequency relation (FFR) is negative. Data on the effect of volatile anesthetics on FFR are very limited.
  
  
  METHODS
  The authors obtained left ventricular tissue from 18 explanted hearts from patients undergoing cardiac transplantation and tissue of 8 organ donors. The negative inotropic effect of halothane, isoflurane, and sevoflurane on isometric force of contraction of isolated muscle preparations at a stimulation frequency of 1 and 3 Hz and the effect of each anesthetic on the FFR were studied. Ryanodine and verapamil were studied for comparison. In addition, the effect of the anesthetics on Ca(2+)-dependent (3)H-ryanodine binding was investigated.
  
  
  RESULTS
  In nonfailing myocardium, halothane was the strongest negative inotropic compound, and the positive FFR was not affected by either drug. In failing myocardium, halothane also showed the strongest negative inotropic effect, but the positive shape of FFR was restored by halothane and ryanodine. In contrast, isoflurane, sevoflurane, and verapamil did not change FFR. Only halothane shifted the Ca(2+)-dependent (3)H-ryanodine binding curve toward lower Ca(2+) concentrations.
  
  
  CONCLUSIONS
  In nonfailing human myocardium, none of the anesthetics affect FFR, but halothane is the strongest negative inotropic compound. In failing myocardium, halothane, but not isoflurane or sevoflurane, restores the positive shape of FFR. Both the more pronounced negative inotropic effect of halothane and the restoration of the positive shape of FFR in failing myocardium in the presence of halothane can be explained by its interaction with the myocardial sarcoplasmic reticulum calcium-release channel.
authors.affiliation: Department of Physiology, Cardiovascular Research Institute, Maastricht, The Netherlands. Schotten@fys.unimaas.nl
authors.forename: U
authors.initials: U
authors.lastname: Schotten
authors.forename: M
authors.initials: M
authors.lastname: Greiser
authors.forename: V
authors.initials: V
authors.lastname: Braun
authors.forename: C
authors.initials: C
authors.lastname: Karlein
authors.forename: F
authors.initials: F
authors.lastname: Schoendube
authors.forename: P
authors.initials: P
authors.lastname: Hanrath
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D009202:Cardiomyopathies / Q000378:metabolism; D046508:Culture Techniques; D004347:Drug Interactions; D004558:Electric Stimulation; D006221:Halothane / Q000494:pharmacology*; D006801:Humans; D007530:Isoflurane / Q000494:pharmacology*; D008738:Methyl Ethers / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D012433:Ryanodine / Q000378:metabolism / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000502:physiology*; D000077149:Sevoflurane; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D018685:Anesthetics, Inhalation; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D008738:Methyl Ethers; D014665:Vasodilator Agents; D012433:Ryanodine; D000077149:Sevoflurane; D014700:Verapamil; D007530:Isoflurane; D006221:Halothane