title: Effects of methacholine infusion on desflurane pharmacokinetics in piglets.
abstract: The data of a corresponding animal experiment demonstrates that nebulized methacholine (MCh) induced severe bronchoconstriction and significant inhomogeneous ventilation and pulmonary perfusion (V̇A/Q̇) distribution in pigs, which is similar to findings in human asthma. The inhalation of MCh induced bronchoconstriction and delayed both uptake and elimination of desflurane (Kretzschmar et al., 2015) [1]. The objective of the present data is to determine V̇A/Q̇ matching by Multiple Inert Gas Elimination Technique (MIGET) in piglets before and during methacholine- (MCh-) induced bronchoconstriction, induced by MCh infusion, and to assess the blood concentration profiles for desflurane (DES) by Micropore Membrane Inlet Mass Spectrometry (MMIMS). Healthy piglets (n=4) under general anesthesia were instrumented with arterial, central venous, and pulmonary artery lines. The airway was secured via median tracheostomy with an endotracheal tube, and animals were mechanically ventilated with intermittent positive pressure ventilation (IPPV) with a FiO2 of 0.4, tidal volume (V T)=10 ml/kg and PEEP of 5cmH2O using an open system. The determination of V.A/Q. was done by MIGET: before desflurane application and at plateau in both healthy state and during MCh infusion. Arterial blood was sampled at 0, 1, 2, 5, 10, 20, and 30 min during wash-in and washout, respectively. Bronchoconstriction was established by MCH infusion aiming at doubling the peak airway pressure, after which wash-in and washout of the anesthetic gas was repeated. Anesthesia gas concentrations were measured by MMIMS. Data were analyzed by ANOVA, paired t-test, and by nonparametric Friedman׳s test and Wilcoxon׳s matched pairs test. We measured airway pressures, pulmonary resistance, and mean paO2 as well as hemodynamic variables in all pigs before desflurane application and at plateau in both healthy state and during methacholine administration by infusion. By MIGET, fractional alveolar ventilation and pulmonary perfusion in relation to the V.A/Q. compartments, data of logSDQ̇ and logSDV̇ (the second moments describing global dispersion, i.e. heterogeneity of distribution) were estimated prior to and after MCh infusion. The uptake and elimination of desflurane was determined by MMIMS.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany ; Department of Surgical Sciences, Hedenstierna Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Alf
authors.initials: A
authors.lastname: Kozian
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany ; Department of Surgical Sciences, Hedenstierna Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Moritz
authors.initials: M
authors.lastname: Kretzschmar
authors.affiliation: Oscillogy ® LLC, Folsom, PA, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Baumgardner
authors.affiliation: Department of Pneumology, Otto-von-Guericke-University Magdeburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Schreiber
authors.affiliation: Department of Medical Sciences, Clinical Physiology, Uppsala University, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Hedenstierna
authors.affiliation: Department of Surgical Sciences, Anesthesia and Intensive Care, Uppsala University, Uppsala, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hachenberg
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany ; Department of Surgical Sciences, Hedenstierna Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schilling
keywords: Alveolar ventilation; Animal model; Arterial blood gas concentration; Bronchoconstriction; Desflurane; Methacholine; Ventilation-/perfusion-mismatch