title: Cytokine release, small airway injury, and parenchymal damage during mechanical ventilation in normal open-chest rats.
abstract: Lung morpho-functional alterations and inflammatory response to various types of mechanical ventilation (MV) have been assessed in normal, anesthetized, open-chest rats. Measurements were taken during protective MV [tidal volume (Vt) = 8 ml/kg; positive end-expiratory pressure (PEEP) = 2.6 cmH(2)O] before and after a 2- to 2.5-h period of ventilation on PEEP (control group), zero EEP without (ZEEP group) or with administration of dioctylsodiumsulfosuccinate (ZEEP-DOSS group), on negative EEP (NEEP group), or with large Vt (26 ml/kg) on PEEP (Hi-Vt group). No change in lung mechanics occurred in the Control group. Relative to the initial period of MV on PEEP, airway resistance increased by 33 +/- 4, 49 +/- 9, 573 +/- 84, and 13 +/- 4%, and quasi-static elastance by 19 +/- 3, 35 +/- 7, 248 +/- 12, and 20 +/- 3% in the ZEEP, NEEP, ZEEP-DOSS, and Hi-Vt groups. Relative to Control, all groups ventilated from low lung volumes exhibited histologic signs of bronchiolar injury, more marked in the NEEP and ZEEP-DOSS groups. Parenchymal and vascular injury occurred in the ZEEP-DOSS and Hi-Vt groups. Pro-inflammatory cytokine concentration in the bronchoalveolar lavage fluid (BALF) was similar in the Control and ZEEP group, but increased in all other groups, and higher in the ZEEP-DOSS and Hi-Vt groups. Interrupter resistance was correlated with indexes of bronchiolar damage, and cytokine levels with vascular-alveolar damage, as indexed by lung wet-to-dry ratio. Hence, protective MV from resting lung volume causes mechanical alterations and small airway injury, but no cytokine release, which seems mainly related to stress-related damage of endothelial-alveolar cells. Enhanced small airway epithelial damage with induced surfactant dysfunction or MV on NEEP can, however, contribute to cytokine production.
authors.affiliation: Istituto di Fisiologia Umana I, Milan, Italy. edgardo.dangelo@unimi.it
authors.forename: Edgardo
authors.initials: E
authors.lastname: D'Angelo
authors.forename: Antonia
authors.initials: A
authors.lastname: Koutsoukou
authors.forename: Patrizia
authors.initials: P
authors.lastname: Della Valle
authors.forename: Guendalina
authors.initials: G
authors.lastname: Gentile
authors.forename: Matteo
authors.initials: M
authors.lastname: Pecchiari
mesh_terms: D000403:Airway Resistance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002245:Carbon Dioxide / Q000097:blood; D016207:Cytokines / Q000378:metabolism*; D003902:Detergents / Q000494:pharmacology; D004338:Drug Combinations; D006863:Hydrogen-Ion Concentration; D007510:Isatin / Q000031:analogs & derivatives / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008170:Lung Compliance; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010100:Oxygen / Q000097:blood; D011175:Positive-Pressure Respiration / Q000009:adverse effects*; D011654:Pulmonary Edema / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics; D013386:Succinates / Q000494:pharmacology; D013990:Tidal Volume; D015854:Up-Regulation; D015919:Ventilators, Negative-Pressure / Q000009:adverse effects*
chemical_list: D016207:Cytokines; D003902:Detergents; D004338:Drug Combinations; D011725:Pyridines; D013386:Succinates; D002245:Carbon Dioxide; C001526:laxagetten 4,4'-diacetoxydiphenylpyridylemethane; D007510:Isatin; D010100:Oxygen