Aortic cross-clamping influences regional net release and uptake rates of tissue-type plasminogen activator in pigs

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Anestesi och intensivvård (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Anesthesiology and Intensive Care (hsv//eng)

Nyckelord

*Anesthesia

Animals

Constriction

Coronary Circulation

Endothelium

Vascular/metabolism

Hemodynamics

Liver Circulation

Pulmonary Circulation

Regional Blood Flow/physiology

Swine

Time Factors

Tissue Plasminogen Activator/*blood

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