title: Lung anatomy, energy load, and ventilator-induced lung injury.
abstract: BACKGROUND
  High tidal volume can cause ventilator-induced lung injury (VILI), but positive end-expiratory pressure (PEEP) is thought to be protective. We aimed to find the volumetric VILI threshold and see whether PEEP is protective per se or indirectly.
  
  
  METHODS
  In 76 pigs (22 ± 2 kg), we examined the lower and upper limits (30.9-59.7 mL/kg) of inspiratory capacity by computed tomography (CT) scan at 45 cmH2O pressure. The pigs underwent a 54-h mechanical ventilation with a global strain ((tidal volume (dynamic) + PEEP volume (static))/functional residual capacity) from 0.45 to 5.56. The dynamic strain ranged from 18 to 100 % of global strain. Twenty-nine pigs were ventilated with end-inspiratory volumes below the lower limit of inspiratory capacity (group "Below"), 38 within (group "Within"), and 9 above (group "Above"). VILI was defined as death and/or increased lung weight.
  
  
  RESULTS
  "Below" pigs did not develop VILI; "Within" pigs developed lung edema, and 52 % died before the end of the experiment. The amount of edema was significantly related to dynamic strain (edema 188-153 × dynamic strain, R (2) = 0.48, p < 0.0001). In the "Above" group, 66 % of the pigs rapidly died but lung weight did not increase significantly. In pigs ventilated with similar tidal volume adding PEEP significantly increased mortality.
  
  
  CONCLUSIONS
  The threshold for VILI is the lower limit of inspiratory capacity. Below this threshold, VILI does not occur. Within these limits, severe/lethal VILI occurs depending on the dynamic component. Above inspiratory capacity stress at rupture may occur. In healthy lungs, PEEP is protective only if associated with a reduced tidal volume; otherwise, it has no effect or is harmful.
authors.affiliation: Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico di Milano, Milan, Italy. alessandro.protti@policlinico.mi.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Protti
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Via Francesco Sforza 35, 20122, Milan, Italy. davide.andreis@unimi.it.
authors.forename: Davide T
authors.initials: DT
authors.lastname: Andreis
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Via Francesco Sforza 35, 20122, Milan, Italy. marta.mil@hotmail.it.
authors.forename: Marta
authors.initials: M
authors.lastname: Milesi
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Via Francesco Sforza 35, 20122, Milan, Italy. japan_ia@hotmail.com.
authors.forename: Giacomo E
authors.initials: GE
authors.lastname: Iapichino
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Via Francesco Sforza 35, 20122, Milan, Italy. massy.mon@gmail.com.
authors.forename: Massimo
authors.initials: M
authors.lastname: Monti
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Via Francesco Sforza 35, 20122, Milan, Italy. bcomini@hotmail.com.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Comini
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Via Francesco Sforza 35, 20122, Milan, Italy. paola.pugni@studenti.unimi.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Pugni
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Via Francesco Sforza 35, 20122, Milan, Italy. valentina.melis1@studenti.unimi.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Melis
authors.affiliation: Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico di Milano, Milan, Italy. alessandro.santini@unimi.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Santini
authors.affiliation: Centro di Ricerche Chirurgiche Precliniche, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy. dondossola.daniele@gmail.com.
authors.forename: Daniele
authors.initials: D
authors.lastname: Dondossola
authors.affiliation: Centro di Ricerche Chirurgiche Precliniche, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy. stefano.gatti@unimi.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gatti
authors.affiliation: Dipartimento dei Servizi, Radiologia, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy. lombluc@libero.it.
authors.forename: Luciano
authors.initials: L
authors.lastname: Lombardi
authors.affiliation: Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy. emiliano.votta@polimi.it.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Votta
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Via Francesco Sforza 35, 20122, Milan, Italy. eleonora.carlesso@unimi.it.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Carlesso
authors.affiliation: Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico di Milano, Milan, Italy. gattinon@policlinico.mi.it.|Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Via Francesco Sforza 35, 20122, Milan, Italy. gattinon@policlinico.mi.it.
authors.forename: Luciano
authors.initials: L
authors.lastname: Gattinoni
keywords: Energy load; Experimental animal model; Inspiratory capacity; Lung stress and strain; Mechanical ventilation; Ventilator-induced lung injury