title: Impact of respiratory pattern on lung mechanics and interstitial proteoglycans in spontaneously breathing anaesthetized healthy rats.
abstract: OBJECTIVE
  The aim of this study was to investigate the effect of different pattern of spontaneous breathing on the respiratory mechanics and on the integrity of the pulmonary extracellular matrix.
  
  
  METHODS
  Experiments were performed on adult healthy rats in which different spontaneously breathing pattern was elicited through administration of two commonly used anaesthetic mixtures: pentobarbital/urethane (P/U) and ketamine/medetomidine (K/M). The animals (five per group) were randomized and left to spontaneously breath for 10 min (P/U-sham; K/M-sham) or for 4h (P/U-4h; K/M-4h), targeting the anaesthesia level to obtain a tidal volume of about 8 mL kg(-1) body wt. At the end of the experiment, lung matrix integrity was assessed through determination of the glycosaminoglycans (GAGs) content in the lung parenchyma.
  
  
  RESULTS
  Compared with K/M, anaesthesia with P/U cocktail induced: (1) a higher respiratory rate and minute ventilation attained with lower P(a) CO(2) ; (2) a higher pressure-time-product and work of breathing per minute; (3) a lower static lung compliance; (4) an increased activation of lung tissue metalloproteases; and (5) greater extraction of pulmonary interstitial GAGs.
  
  
  CONCLUSIONS
  This study suggests that the breathing pattern induced by the different anaesthetic regimen may damage the pulmonary interstitium even during spontaneous breathing at physiological tidal volumes.
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Insubria, Varese, Italy.  
authors.forename: A
authors.initials: A
authors.lastname: Moriondo
authors.forename: C
authors.initials: C
authors.lastname: Marcozzi
authors.forename: F
authors.initials: F
authors.lastname: Bianchin
authors.forename: A
authors.initials: A
authors.lastname: Passi
authors.forename: F
authors.initials: F
authors.lastname: Boschetti
authors.forename: S
authors.initials: S
authors.lastname: Lattanzio
authors.forename: P
authors.initials: P
authors.lastname: Severgnini
authors.forename: P
authors.initials: P
authors.lastname: Pelosi
authors.forename: D
authors.initials: D
authors.lastname: Negrini
mesh_terms: D000777:Anesthetics / Q000378:metabolism; D000818:Animals; D045604:Extracellular Fluid / Q000737:chemistry; D005109:Extracellular Matrix / Q000737:chemistry*; D006025:Glycosaminoglycans / Q000032:analysis; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000201:enzymology / Q000502:physiology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000378:metabolism; D008962:Models, Theoretical; D011509:Proteoglycans / Q000032:analysis* / Q000302:isolation & purification; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration; D012129:Respiratory Function Tests; D015656:Respiratory Mechanics / Q000502:physiology*
chemical_list: D000777:Anesthetics; D006025:Glycosaminoglycans; D015850:Interleukin-6; D011509:Proteoglycans; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9