Systemic levels and preportal organ release of tissue-type plasminogen activator are enhanced by PEEP in the pig.
BACKGROUND
Endothelium-derived tissue-type plasminogen activator, t-PA, is the key enzyme in the initiation of endogenous thrombolysis. Plasma levels of t-PA increase in response to sympatho-adrenergic activation. In the mesenteric vascular bed an increased norepinephrine spillover has been observed during positive end-expiratory pressure ventilation, PEEP. This experimental study examines the effects of PEEP-induced alterations on regional release rates and systemic levels of t-PA in vivo.


METHODS
The protocol included measurements of arterio-venous concentration gradients of t-PA and the respective plasma flow across the pulmonary, coronary, hepatic and preportal vascular beds, in pigs, during zero-PEEP and at 2, 4 and 10 min after the application of a PEEP of 10 cm H2O. Both total plasma t-PA antigen (ELISA with a porcine t-PA standard) and active t-PA (spectrophotometric functional assay) were determined.


RESULTS
During zero-PEEP, a high preportal basal net release and hepatic net uptake of total t-PA was observed. With PEEP, the magnitude of the preportal net release of t-PA was markedly enhanced (+24+/-5%), as was hepatic net uptake (+21+/-8%), simultaneously to a significant decrease in liver plasma flow (-30+/-2%). PEEP-induced alterations in active t-PA mirrored those observed in total t-PA. No significant net fluxes of total or active t-PA were observed across the coronary or the pulmonary vascular beds.


CONCLUSIONS
Clinically used levels of PEEP induce increases in net release of endothelially derived t-PA within preportal organs. The application of PEEP is associated with increased systemic levels of total and active t-PA, in spite of a simultaneous increase in hepatic net uptake, indicating that the preportal vascular bed can not account for the systemic t-PA response.
Seeman-Lodding
H
H
Department of Anesthesiology and Intensive Care, Sahlgrenska University Hospital, Göteborg, Sweden.
Häggmark
S
S
Jern
C
C
Jern
S
S
Johansson
G
G
Winsö
O
O
Biber
B
B
D000818:Animals; D001011:Aorta; D003331:Coronary Vessels; D006439:Hemodynamics; D006503:Hepatic Veins; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011169:Portal Vein; D011175:Positive-Pressure Respiration; D011651:Pulmonary Artery; D013552:Swine; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000378:metabolism*; D014680:Veins
D010959:Tissue Plasminogen Activator