title: Isoflurane and halothane impair both systolic and diastolic function in the newborn pig.
abstract: OBJECTIVE
  Volatile anaesthetics have considerable effects on diastolic relaxation in the adult myocardium. We hypothesized that isoflurane (1) and halothane (H) may have even greater effects on diastolic function in the newborn, as the newborn heart has increased passive stiffness and altered calcium handling relative to the adult. Using a newborn pig model, we compared I and H at three clinically relevant concentrations with respect to both systolic and diastolic function.
  
  
  METHODS
  Sixteen newborn pigs were randomized for study at control (background fentanyl 100 micrograms.kg-1.hr-1 and 0.5, 1.0 and 1.5 MAC of I (n = 8) or H (n = 8). Temperature, arterial blood gases, and LVEDP were controlled. Left ventricular pressure (LVP) was monitored continuously and LV anterior-posterior dimension was determined by using sonomicrometry crystals. Systolic function was assessed by peak positive dP/dT (dP/dTmax) and the slope of the end-systolic pressure-dimension (ESP-D) relationship. Diastolic relaxation was given by peak negative dP/dT (-dP/dTmax) and the time constant for ventricular relaxation (tau). Left ventricular stiffness was calculated from the slope of the end-diastolic pressure-dimension (EDP-D) relationship.
  
  
  RESULTS
  At equal MAC concentrations, I and H were identical in effect for every variable studied. Systolic function was depressed at all anaesthetic concentrations. Control dP/dTmax (I:1815 +/- 561 (SD) mmHg.sec-1, H:1841 +/- 509) decreased to 832 +/- 341 with 1.5 MAC I and 691 +/- 127 with 1.5 MAC H (P < 0.05 vs control). ESP-D slope decreased from 62 +/- 31 mmHg.mm-1 at control to 15 +/- 11 with 1.5 MAC I and from 79 +/- 16 to 37 +/- 15 with 1.5 MAC H (P < 0.05 vs control). Diastolic function was affected only at higher MAC anaesthesia. Control tau increased from 18.0 +/- 6 msec to 29.1 +/- 7.5 with 1.5 MAC I and from 20.8 +/- 5.9 to 30.0 +/- 11.3 with 1.5 MAC H (P < 0.05). EDP-D slope was increased at both 1 and 1.5 MAC anaesthesia. EDP-D slope increased from 0.16 +/- 0.24 mmHg.mm-1 at control to 0.58 +/- 0.46 with I MAC I and from 0.16 +/- 11 to 0.50 +/- 0.35 with 1 MAC H. The -dP/dTmax decreased at every MAC level of anaesthesia.
  
  
  CONCLUSIONS
  These combined systolic and diastolic effects help to explain the increased sensitivity of the newborn myocardium to volatile anaesthetics.
authors.affiliation: Department of Anaesthesia, University of Manitoba, Winnipeg, Canada. graham@bldghsc.lan1.umanitoba.ca
authors.forename: M R
authors.initials: MR
authors.lastname: Graham
authors.forename: D B
authors.initials: DB
authors.lastname: Thiessen
authors.forename: W A
authors.initials: WA
authors.lastname: Mutch
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D003971:Diastole / Q000187:drug effects*; D006221:Halothane / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D013552:Swine; D013599:Systole / Q000187:drug effects*
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane; D006221:Halothane