Bioscience, AstraZeneca R&D Mölndal, Sweden.
Thromb Res. 2010 Mar;125(3):e106-9. doi: 10.1016/j.thromres.2009.10.004. Epub 2009 Nov 20.
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.
Accordingly, we hypothesised that splanchnic t-PA release might decrease after an initial peak during maintained and long-lasting sympathetic stimulation.
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.
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.
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.
在肠系膜血管床中有大量组织型纤溶酶原激活物(t-PA)的局部释放,而这种释放会在高交感神经张力下增加。冠状动脉的 t-PA 释放也很显著,这种释放会在心脏神经刺激期间以及局部心肌缺血 10 分钟后的再灌注期间增加。然而,通过反复的心肌缺血/再灌注循环,冠状动脉 t-PA 的释放会逐渐减少。
因此,我们假设在持续和长期的交感神经刺激期间,初始高峰过后,肠系膜 t-PA 的释放可能会减少。
在 6 只麻醉猪中,通过放血(30 分钟内放血 20-25 毫升/公斤)来增加交感神经张力。在随后的 2 小时期间,每隔 20 分钟抽取门静脉(引流肠系膜血管床)和动脉血样,并连续记录门静脉血流量,以估计肠系膜血管床中的 t-PA 释放。
放血后,平均动脉血压稳定在 50 至 65mmHg,门静脉血流约为基线值的 50%,相对稳定的血液动力学条件得以维持。净肠系膜 t-PA 释放在放血后 40 分钟达到高峰,但随后逐渐向基线值下降。动脉 t-PA 活性在出血期后升高,并在观察期末达到峰值。
在增加交感神经刺激期间,净肠系膜 t-PA 释放仅短暂增加,而动脉 t-PA 水平保持升高。在强烈和长期的交感神经刺激下,缺乏持续增加的肠系膜 t-PA 释放可能会增加静脉内肠系膜血栓形成的风险。