title: The mechanism of halothane-induced myocardial depression. Altered diastolic mechanics versus impaired contractility.
abstract: Although halothane has been shown to depress left ventricular function, it remains a common alternative to narcotic anesthesia in cardiac operations. To clarify the mechanism by which this functional depression occurs (direct decrease in contractility versus altered diastolic compliance), we studied seven dogs in the closed-chest state following instrumentation with ultrasonic dimension transducers to measure left ventricular anteroposterior diameter and micromanometers to measure transmural left ventricular pressure. Ventricular volumes were varied with transient vena caval occlusions in the awake state and following general anesthesia with halothane at 1% and 2% end-tidal concentrations. Ventricular contractility was assessed by the slope of the end-systolic pressure-diameter relationship (EES). Following normalization of end-diastolic diameters with a Lagrangian strain definition (E), diastolic compliance was assessed by fitting end-diastolic pressure-strain data to the exponential: P = alpha (e beta E -1), where alpha and beta are nonlinear elastic coefficients. Halothane was found to produce a significant, dose-dependent decrease in EES from 10.6 +/- 0.6 control to 6.7 +/- 0.4 at 1% halothane and 4.2 +/- 0.5 at 2% halothane (p less than 0.05, control versus both 1% and 2% halothane). Furthermore, halothane at the concentrations studied did not significantly alter alpha and beta nor significantly shift the exponential end-diastolic pressure-strain curve from control. These data indicate that halothane produces a direct, severe depression of left ventricular contractility without primarily altering the diastolic mechanical properties of the myocardium.
mesh_terms: D000818:Animals; D003187:Compliance; D003864:Depression, Chemical; D003971:Diastole / Q000187:drug effects*; D004285:Dogs; D006221:Halothane / Q000009:adverse effects*; D006352:Heart Ventricles / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D011312:Pressure; D013599:Systole / Q000187:drug effects*
chemical_list: D006221:Halothane