Release of tissue-type plasminogen activator (t-PA) in the splanchnic circulation of the anaesthetised pig during high sympathetic tone

Abstract

Background There is a substantial local release of tissue-type plasminogen activator (t-PA) in the splanchnic vascular bed, and this release is increased at high sympathetic tone. Coronary t-PA release is also significant, and this release increases during cardiac nerve stimulation and during reperfusion after 10 min of local myocardial ischemia. However, by repeated cycles of myocardial ischemia/reperfusion coronary t-PA release progressively declines. Objectives Accordingly, we hypothesised that splanchnic t-PA release might decrease after an initial peak during maintained and long-lasting sympathetic stimulation. Methods In 6 anaesthetised pigs sympathetic tone was augmented by bleeding (20–25 mL/kg over 30 minutes). During the subsequent 2 hours period portal vein (draining the splanchnic vasular bed) - and arterial blood samples were drawn every 20 min and portal vein blood flow was recorded continuously in order to estimate t-PA release in the splanchnic vascular bed. Results Relatively stable haemodynamic conditions were obtained after bleeding with mean arterial blood pressure at 50 to 65 mmHg and a portal vein flow at about the 50% of baseline value. Net splanchnic t-PA release rose to a peak 40 min after bleeding, but subsequently declined towards baseline values. Arterial t-PA activity rose after the bleeding period and to a peak value at end of the observation period. Conclusions Net splanchnic t-PA release increased only transiently during the period with increased sympathetic stimulation, whereas the arterial t-PA level remained elevated. During a strong and longlasting sympathetic stimulation the lack of a continuously augmented splanchnic t-PA release might increase the risk for intravenous splanchnic thrombosis.