title: Direct negative inotropic and lusitropic effects of sevoflurane.
abstract: BACKGROUND
  Volatile anesthetics depress left ventricular mechanical performance during multiple phases of the cardiac cycle. The effects of sevoflurane on systolic and diastolic function have yet to be fully evaluated. This investigation characterized the systemic and coronary hemodynamic, inotropic, and lusitropic actions of sevoflurane in chronically instrumented dogs in the presence and absence of autonomic nervous system (ANS) reflexes.
  
  
  METHODS
  Because ANS activity may influence the actions of volatile anesthetics in vivo, experiments were conducted in both ANS-intact and ANS-blocked animals. Eighteen experiments were performed in nine dogs chronically instrumented for measurement of aortic and left ventricular pressure, rate of change of left ventricular pressure, subendocardial segment length, diastolic coronary blood flow velocity, and cardiac output. The preload recruitable stroke work slope was used to assess myocardial contractility. Diastolic function was evaluated by a time constant of isovolumic relaxation, maximum segment lengthening velocity during rapid ventricular filling, and a regional chamber stiffness constant. Dogs were assigned to receive sevoflurane with or without pharmacologic blockade of the ANS in a random fashion. On separate experimental days, systemic and coronary hemodynamics and left ventricular pressure--segment length diagrams and waveforms were recorded in the conscious state and during sevoflurane anesthesia (1.0, 1.25, 1.5, and 1.75 MAC).
  
  
  RESULTS
  In dogs with intact ANS reflexes, sevoflurane caused significant (P < 0.05) increases in heart rate and dose-related decreases in mean arterial pressure, left ventricular systolic pressure, cardiac output, and diastolic coronary vascular resistance. Sevoflurane also decreased myocardial contractility (preload recruitable stroke work slope 96 +/- 4 in the conscious state to 42 +/- 3 mmHg at 1.75 MAC). Sevoflurane prolonged isovolumic relaxation (time constant of isovolumic relaxation 35 +/- 1 in the conscious state to 51 +/- 3 ms at 1.75 MAC) and decreased rapid ventricular filling (maximum segment lengthening velocity 40.2 +/- 6.0 in the conscious state to 21.8 +/- 3.8 mm.s-1 at 1.75 MAC) without affecting regional chamber stiffness. Sevoflurane caused similar alterations in functional indices of left ventricular systolic and diastolic performance in autonomically blocked dogs.
  
  
  CONCLUSIONS
  Sevoflurane caused direct negative inotropic and lusitropic effects in chronically instrumented dogs with and without ANS blockade.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
authors.forename: C P
authors.initials: CP
authors.lastname: Harkin
authors.forename: P S
authors.initials: PS
authors.lastname: Pagel
authors.forename: J R
authors.initials: JR
authors.lastname: Kersten
authors.forename: D A
authors.initials: DA
authors.lastname: Hettrick
authors.forename: D C
authors.initials: DC
authors.lastname: Warltier
mesh_terms: D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001340:Autonomic Nerve Block; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003864:Depression, Chemical; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D008738:Methyl Ethers; D009200:Myocardial Contraction / Q000187:drug effects*; D000077149:Sevoflurane; D013318:Stroke Volume; D013599:Systole / Q000187:drug effects / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D000777:Anesthetics; D002316:Cardiotonic Agents; D004987:Ethers; D008738:Methyl Ethers; D000077149:Sevoflurane