Mechanical ventilation and hemorrhagic shock-resuscitation interact to increase inflammatory cytokine release in rats.
OBJECTIVE
To determine whether hemorrhagic shock and resuscitation (HSR) and high lung stress during mechanical ventilation interact to augment lung and systemic inflammatory responses and whether their sequence affects these responses.


METHODS
Prospective, randomized, controlled animal study.


METHODS
Research laboratory.


METHODS
Fifty-six male Wistar rats.


METHODS
Controls were immediately killed after anesthesia. High lung stress was produced by mechanical ventilation with high tidal volume of 30 mL/kg and no positive end-expiratory pressure (HV) for 2 hrs. HSR consisted of lessening systemic arterial pressure to 30 mm Hg for 1 hr followed by reinjection of the withdrawn blood. Experimental groups consisted of HSR only and HSR preceded or followed by HV or conventional mechanical ventilation.


RESULTS
Interleukin-1beta, interleukin-6, and macrophage inhibitory protein 2 were determined in lung homogenate, bronchoalveolar lavage fluid, and plasma. HV ventilation alone did not increase plasma or lung cytokine content compared with controls. HSR significantly increased all mediators in lungs and plasma but not macrophage inhibitory protein 2 in plasma. Conventional ventilation, applied either before or after HSR, did not influence lung or systemic mediator release, whereas HV significantly increased mediator release when combined with HSR whatever the sequence of injuries. Lung mediator content was significantly higher in animals ventilated with HV before the HSR stress than in animals submitted to HSR and then ventilated with HV. Plasma macrophage inhibitory protein 2 concentrations followed the same pattern.


CONCLUSIONS
This study shows that HSR and high lung tissue stress interact to increase lung and systemic release of inflammatory mediators in a way that depends on their sequence. Previous injury may sensitize lungs to inadequate mechanical ventilation, but inadequate mechanical ventilation may also sensitize lungs to postoperative complications.
Bouadma
Lila
L
INSERM, U773, Centre de Recherche Bichat Beaujon CRB3, Paris.
Dreyfuss
Didier
D
Ricard
Jean-Damien
JD
Martet
Geneviève
G
Saumon
Georges
G
D000818:Animals; D054426:Chemokine CXCL2 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000276:immunology*