Submitted on July 26, 2007
Accepted on October 18, 2007
Cytokine release, small airway injury, and parenchymal damage during mechanical ventilation in normal open-chest rats
Edgardo D'Angelo1*, Antonia Koutsoukou2, Patrizia Della Valle3, Guendalina Gentile4, and Matteo Pecchiari5
1 Istituto di Fisiologia Umana I, University of Milan, Milan, Italy
2 Critical Care Department, Evangelismos Hospital, University of Athens, Athens, Greece
3 Servizio di Coagulazione, IRCCS Ospedale San Raffaele, Milan, Italy
4 Istituto di Medicina Legale, Universita degli Studi di Milano, Milan, Italy
5 Istituto di Fisiologia Umana I, Universita degli Studi di Milano, Milan, Italy
* To whom correspondence should be addressed. E-mail: edgardo.dangelo{at}unimi.it.
Lung morpho-functional alterations and inflammatory response to various types of mechanical ventilation (MV) have been assessed in normal, anestetized, open-chest rats. Measurements were taken during protective MV (VT=8 ml·kg-1 PEEP=2.6 cm H2O) before and after a 2-2
hours 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-1) 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. Rint was correlated with indices 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 NEEP can however contribute to cytokine production.
