Effect of activated protein C on pulmonary blood flow and cytokine production in experimental acute lung injury.
OBJECTIVE
In acute lung injury (ALI) activated protein C (APC) may reopen occluded lung vessels and minimize lung inflammation. We aimed at assessing the effect of APC on regional lung perfusion, aerated lung volume, cytokine production and oxygenation in experimental ALI.


METHODS
Prospective, controlled study in an imaging facility.


METHODS
Pigs tracheotomized and mechanically ventilated.


METHODS
Pigs were randomly given intravenously APC (n = 8) or saline (n = 8). Thirty minutes later, ALI was induced by injecting oleic acid.


RESULTS
Lung perfusion and aerated lung volume measured with positron emission tomography, plasma cytokines and arterial blood gas were determined just before ALI and 110 and 290 min thereafter. Lung cytokines were measured at the end of the experiment. PaO2 under F I O2 1 was significantly lower in the APC group before lung injury (473+/-129 vs. 578+/-54 mmHg) and 110 min (342+/-138 vs. 446+/-103 mmHg) and 290 min (303+/-171 vs. 547+/-54 mmHg) thereafter (p < 0.05). Lung perfusion nonsignificantly tended to redistribute towards dorsal lung regions with APC. Total aerated lung volume was not different between APC and control before ALI (10.0+/-1.5 vs. 11.0+/-2.5 ml/kg) (p > 0.05) or thereafter. Plasma IL-6 and IL-8 at 110 min were greater with APC (p < 0.05).


CONCLUSIONS
In contrast to studies using other models, pretreatment with APC was associated with worsening oxygenation in the present investigation. This might be due to ventilation-perfusion mismatch, with more perfusion to dependent nonaerated areas.
Service de Réanimation Médicale, Hôpital de la Croix Rousse, 103 Grande Rue de la Croix Rousse, 69004, Lyon, France.
Jean-Christophe
JC
Richard
Fabienne
F
Bregeon
Véronique
V
Leray
Didier
D
Le Bars
Nicolas
N
Costes
Christian
C
Tourvieille
Franck
F
Lavenne
Mojgan
M
Devouassoux-Shisheboran
Gerard
G
Gimenez
Claude
C
Guerin
D000818:Animals; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D005602:France; D008168:Lung / Q000098:blood supply*; D049268:Positron-Emission Tomography; D011486:Protein C / Q000008:administration & dosage / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D012128:Respiratory Distress Syndrome; D013552:Swine; D014692:Ventilation-Perfusion Ratio
D016207:Cytokines; D011486:Protein C