Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.
Am J Physiol Regul Integr Comp Physiol. 2014 Jul 1;307(1):R75-81. doi: 10.1152/ajpregu.00450.2013. Epub 2014 Apr 30.
Effective treatment of sepsis remains a significant challenge in intensive care units. During sepsis, there is widespread activation of the sympathetic nervous system, which is thought to have both beneficial and detrimental effects. The sympathoexcitation is thought to be partly due to the developing hypotension, but may also be a response to the inflammatory mediators released. Thus, we investigated whether intracarotid infusion of prostaglandin E2 (PGE2) induced similar cardiovascular changes to those caused by intravenous infusion of Escherichia coli in sheep and whether inhibition of prostaglandin synthesis, with the nonselective cyclooxygenase inhibitor indomethacin, administered at 2 and 8 h after the onset of sepsis, reduced sympathetic nerve activity (SNA), and heart rate (HR). Studies were performed in conscious sheep instrumented to measure mean arterial pressure (MAP), HR, cardiac SNA (CSNA), and renal SNA (RSNA). Intracarotid infusion of PGE2 (50 ng·kg(-1)·min(-1)) increased temperature, CSNA, and HR, but not MAP or RSNA. Sepsis, induced by infusion of E. coli, increased CSNA, but caused an initial, transient inhibition of RSNA. At 2 h of sepsis, indomethacin (1.25 mg/kg bolus) increased MAP and caused reflex decreases in HR and CSNA. After 8 h of sepsis, indomethacin did not alter MAP, but reduced CSNA and HR, without altering baroreflex control. These findings indicate an important role for prostaglandins in mediating the increase in CSNA and HR during the development of hyperdynamic sepsis, whereas prostaglandins do not have a major role in determining the early changes in RSNA.
在重症监护病房中，脓毒症的有效治疗仍然是一个重大挑战。在脓毒症期间，交感神经系统广泛激活，这被认为既有有益的影响，也有有害的影响。交感兴奋被认为部分是由于低血压的发展，但也可能是对释放的炎症介质的反应。因此，我们研究了在绵羊中，经颈动脉内输注前列腺素 E2（PGE2）是否会引起与静脉内输注大肠杆菌引起的类似心血管变化，以及在脓毒症发作后 2 和 8 小时给予非选择性环氧化酶抑制剂吲哚美辛是否会抑制前列腺素合成，从而降低交感神经活性（SNA）和心率（HR）。研究在清醒绵羊中进行，这些绵羊被仪器化以测量平均动脉压（MAP）、HR、心脏 SNA（CSNA）和肾脏 SNA（RSNA）。经颈动脉内输注 PGE2（50ng·kg(-1)·min(-1)）会升高体温、CSNA 和 HR，但不会升高 MAP 或 RSNA。通过输注大肠杆菌引起的脓毒症会增加 CSNA，但会导致 RSNA 的初始短暂抑制。在脓毒症的 2 小时，吲哚美辛（1.25mg/kg 推注）会升高 MAP，并引起 HR 和 CSNA 的反射性降低。在脓毒症 8 小时后，吲哚美辛不会改变 MAP，但会降低 CSNA 和 HR，而不会改变压力反射控制。这些发现表明前列腺素在介导高动力性脓毒症发展过程中 CSNA 和 HR 的增加中起重要作用，而前列腺素在决定 RSNA 的早期变化中没有主要作用。
