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

1 Istituto di Fisiologia Umana I and 4 Istituto di Medicina Legale, Università di Milano, Milan, Italy; 2 Critical Care Department, University of Athens, Greece; 3 Servizio 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 (V T ) = 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 V T (26 ml/kg) on PEEP (Hi-V T 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-V T 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-V T 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-V T 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 Address for reprint requests and other correspondence: E. D'Angelo, Istituto di Fisiologia Umana I, via Mangiagalli 32, 20133 Milan, Italy (e-mail: edgardo.dangelo{at}unimi.it )