Pulmonary net release of tissue-type plasminogen activator during porcine primary and secondary acute lung injury.
BACKGROUND
Tissue-type plasminogen activator (tPA) is a key mediator of fibrinolysis. Matching of pulmonary perfusion and ventilation is a critical denominator of oxygenation in acute lung injury (ALI). This study investigates pulmonary venoarterial plasma tPA gradients in association with acute ALI induced by bronchoalveolar lavage (BAL) and endotoxinemia (ETX).


METHODS
Twenty-one anaesthetized, ventilated pigs were allocated to control (CTRL, n=5), bronchoalveolar saline lavage (BAL, n=8) or infusion of Escherichia coli endotoxin (ETX, n=8). Total tPA was analyzed in plasma (ELISA calibrated for porcine tPA). The inflammatory response was assessed by TNFa levels (ELISA). All variables were assessed at baseline and 2 h following ALI.


RESULTS
Bronchoalveolar lavage and ETX induced similar increases in pulmonary shunt whereas pulmonary vascular resistance was significantly more increased in ETX animals. Cardiac output remained stable in BAL animals but decreased in ETX animals. The pulmonary venoarterial tPA plasma gradient increased in ETX animals, yielding a positive pulmonary net flux of tPA, which was absent in BAL animals. TNFalpha levels increased in ETX, but not in BAL, animals. A significant correlation was observed between TNFalpha and tPA plasma levels in ETX animals. All variables remained unchanged in CTRL animals.


CONCLUSIONS
Plasma changes of tPA levels support a pulmonary release of tPA in early experimental ALI induced by acute ETX but not lavage, and are related to the inflammatory response. Despite increased vascular fibrinolytic capacity in ETX animals, pulmonary dysfunction was not different from BAL animals. The results demonstrate the close relation between inflammation and coagulation in early ALI.
Nyberg
A
A
Department of Anaesthesiology and Intensive Care, Sahlgrenska University Hospital, Göteborg, Sweden.
Fagerberg
A
A
Ahlqvist
M
M
Jern
C
C
Seeman-Lodding
H
H
Aneman
A
A
D000818:Animals; D005260:Female; D008168:Lung / Q000378:metabolism*; D008297:Male; D012128:Respiratory Distress Syndrome / Q000378:metabolism*; D013552:Swine; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D014409:Tumor Necrosis Factor-alpha; D010959:Tissue Plasminogen Activator