title: Mechanoenergetics of the negative inotropism of isoflurane in the canine left ventricle. No O2 wasting effect.
abstract: BACKGROUND
  The mechanisms underlying the negative inotropic effects of isoflurane are incompletely understood. One suggested mechanism is that isoflurane may decrease Ca2+ sensitivity of contractile proteins. If so, more free calcium would be needed to activate contractile proteins to the same degree, which would impose a greater requirement for myocardial oxygen consumption used in the cycling of calcium. In this study, the authors use the excised, cross-circulated, canine heart model and the volume servopump technique to measure the effects of isoflurane on Emax (a contractile index) and on the relationship between pressure-volume area (PVA, a measure of total mechanical energy) and myocardial oxygen consumption per beat (VO2).
  
  
  METHODS
  Effects of intracoronary isoflurane infused via a precoronary oxygenator on myocardial mechanoenergetics were studied during isovolumic contractions. The authors measured left ventricular (LV) pressure, LV volume, coronary flow, and arteriovenous oxygen content difference and computed Emax, VO2 and PVA at 0, 1.0, 1.5, and 2.0% isoflurane. From these data, the authors obtained oxygen costs of PVA and Emax in control subjects and in those receiving 2.0% isoflurane.
  
  
  RESULTS
  Emax, PVA, and VO2 dose-dependently decreased by similar degrees (P < 0.05). Isoflurane did not change the oxygen costs at 1.5% and 2.0% concentration (P < 0.05).
  
  
  CONCLUSIONS
  These mechanoenergetic findings suggest that the primary method by which isoflurane decreases contractility is not by decreasing Ca2+ sensitivity of contractile proteins but mainly by decreasing Ca2+ handling in the excitation-contraction coupling without myocardial oxygen wasting effect.
authors.affiliation: Department of Physiology II, Nara Medical University, Kashihara, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nakayama
authors.forename: M
authors.initials: M
authors.lastname: Takaki
authors.forename: K
authors.initials: K
authors.lastname: Kohno
authors.forename: J
authors.initials: J
authors.lastname: Araki
authors.forename: H
authors.initials: H
authors.lastname: Suga
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D004285:Dogs; D006352:Heart Ventricles / Q000187:drug effects* / Q000503:physiopathology; D007530:Isoflurane / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D010100:Oxygen / Q000502:physiology
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane; D010100:Oxygen; D002118:Calcium