title: Aortic cross-clamping influences regional net release and uptake rates of tissue-type plasminogen activator in pigs.
abstract: BACKGROUND
  The key regulator of intravascular fibrinolysis, tissue-type plasminogen activator (t-PA), is released from a dynamic endothelial storage pool. The aim of the study was to investigate regional t-PA net release and uptake rates in response to infra-renal aortic cross-clamping (AXC) and declamping (DC).
  
  
  METHODS
  Anesthetized pigs were studied during 5 min of AXC, followed by a 35-min declamping (DC) period. Arterio-venous concentration gradients of total and active t-PA, as well as respective plasma flows, were simultaneously obtained across the preportal, hepatic, coronary and pulmonary vascular beds. Plasma levels of total t-PA (ELISA with purified porcine t-PA as standard), and active t-PA (spectrophotometric functional assay) were determined.
  
  
  RESULTS
  Prior to AXC, we found a high net release rate of total t-PA across the preportal vascular bed (1700 ng.min-1 P < 0.001), and a high hepatic net uptake (4900 ng.min-1, P < 0.001), while coronary and pulmonary t-PA net fluxes were small and variable. AXC per se did not induce significant alterations in net fluxes of t-PA. Following DC, preportal and coronary net releases of total t-PA increased (to 2900 ng.min-1 and 60 ng.min-1, respectively). Despite an increase in hepatic net uptake of total t-PA (to 6100 ng.min-1) after DC, a significant increase in hepatic venous total t-PA occurred.
  
  
  CONCLUSIONS
  The release and uptake of t-PA is indicated to be dynamic and organ-specific. DC induces an acute profibrinolytic reaction in preportal organs. The high hepatic t-PA uptake capacity restricts preportal profibrinolytic events to affect the systemic circulation.
authors.affiliation: Dept. of Anesthesiology and Intensive Care, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Seeman-Lodding
authors.forename: S
authors.initials: S
authors.lastname: Häggmark
authors.forename: C
authors.initials: C
authors.lastname: Jern
authors.forename: S
authors.initials: S
authors.lastname: Jern
authors.forename: G
authors.initials: G
authors.lastname: Johansson
authors.forename: O
authors.initials: O
authors.lastname: Winsö
authors.forename: B
authors.initials: B
authors.lastname: Biber
mesh_terms: D000758:Anesthesia; D000818:Animals; D003250:Constriction; D003326:Coronary Circulation; D004730:Endothelium, Vascular / Q000378:metabolism; D006439:Hemodynamics; D008102:Liver Circulation; D011652:Pulmonary Circulation; D012039:Regional Blood Flow / Q000502:physiology; D013552:Swine; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood*
chemical_list: D010959:Tissue Plasminogen Activator