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This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 104/1/41    most recent 00805.2007v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by D'Angelo, E. Articles by Pecchiari, M. Search for Related Content PubMed PubMed Citation Articles by D'Angelo, E. Articles by Pecchiari, M.

Cytokine release, small airway injury, and parenchymal damage during mechanical ventilation in normal open-chest rats

¹Istituto di Fisiologia Umana I and ⁴Istituto di Medicina Legale, Università di Milano, Milan, Italy; ²Critical Care Department, University of Athens, Greece; ³Servizio di Coagulazione, IRCCS Ospedale San Raffaele, Milan, Italy

Submitted 26 July 2007 ; accepted in final form 18 October 2007

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 cmH₂O] 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.

lung mechanics; recruitment-derecruitment of lung units; microvascular damage; inflammation