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.