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


OBJECTIVE
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 vascular 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.
Björkman
Jan-Arne
JA
Bioscience, AstraZeneca R&D Mölndal, Sweden. Jan-Arne.Bjorkman@astrazeneca.com
Ilebekk
Arnfinn
A
Jern
Christina
C
D000818:Animals; D008102:Liver Circulation / Q000502:physiology; D011169:Portal Vein / Q000378:metabolism; D012039:Regional Blood Flow; D013152:Splanchnic Circulation / Q000502:physiology*; D013552:Swine / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000502:physiology*; D010959:Tissue Plasminogen Activator / Q000097:blood* / Q000378:metabolism*
D010959:Tissue Plasminogen Activator