Schears Gregory, Zaitseva Tatiana, Schultz Steven, Greeley William, Antoni Diego, Wilson David F, Pastuszko Anna
Department of Anesthesiology and Critical Care, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Eur J Cardiothorac Surg. 2006 Feb;29(2):168-74. doi: 10.1016/j.ejcts.2005.11.010. Epub 2006 Jan 11.
To investigate the possible neuroprotective effects of selective cerebral perfusion (SCP) during deep hypothermic circulatory arrest on brain oxygenation and metabolism in newborn piglets.
Newborn piglets 2-4 days of age, anesthetized and mechanically ventilated, were used for the study. The animals were placed on cardiopulmonary bypass, cooled to 18 degrees C and put on SCP (20 ml/(kg min)) for 90 min. After rewarming, the animals were monitored through 2h of recovery. Oxygen pressure in the microvasculature of the cortex was measured by oxygen-dependent quenching of phosphorescence. The extracellular level of dopamine in striatum was measured by microdialysis and hydroxyl radicals by ortho-tyrosine levels. Levels of phosphorylated cAMP response element binding protein (pCREB) in striatal tissue were measured by Western blots using antibodies specific for phosphorylated CREB. The results are presented as mean+/-SD (p<0.05 was significant).
Pre-bypass cortical oxygen pressure was 48.9+/-11.3 mmHg and during the first 5 min of SCP, the peak of the histogram, corrected to 18 degrees C, decreased to 11.2+/-3.8 mmHg (p<0.001) and stayed near that value to the end of bypass. The mean value for the peak of the histograms measured at the end of SCP was 8+/-3 mmHg (p<0.001). SCP completely prevented the deep hypothermic circulatory arrest-dependent increase in extracellular dopamine and hydroxyl radicals. After SCP, there was a statistically significant increase in pCREB immunoreactivity (534+/-60%) compared to the sham-operated group (100+/-63%, p<0.005). Measurements of total CREB showed that SCP did induce a statistically significant increase in CREB as compared to sham-operated animals (168+/-31%, p<0.05).
SCP, as compared to DHCA, improved cortical oxygenation and prevented increases in the extracellular dopamine and hydroxyl radicals. The increase in pCREB in the striatum following SCP may contribute to improved cellular recovery after this procedure.
研究深低温停循环期间选择性脑灌注(SCP)对新生仔猪脑氧合及代谢的可能神经保护作用。
选用2 - 4日龄的新生仔猪,麻醉后进行机械通气,用于本研究。将动物置于体外循环,冷却至18℃,并给予SCP(20 ml/(kg·min))90分钟。复温后,对动物进行2小时的恢复监测。通过磷光氧依赖性猝灭法测量皮质微血管中的氧分压。通过微透析测量纹状体中多巴胺的细胞外水平,通过邻酪氨酸水平测量羟自由基。使用针对磷酸化CREB的特异性抗体,通过蛋白质免疫印迹法测量纹状体组织中磷酸化环磷酸腺苷反应元件结合蛋白(pCREB)的水平。结果以平均值±标准差表示(p<0.05具有显著性)。
体外循环前皮质氧分压为48.9±11.3 mmHg,在SCP的前5分钟,校正至18℃后的直方图峰值降至11.2±3.8 mmHg(p<0.001),并在体外循环结束时维持在该值附近。SCP结束时测量的直方图峰值平均值为8±3 mmHg(p<0.001)。SCP完全阻止了深低温停循环依赖性细胞外多巴胺和羟自由基的增加。与假手术组(100±63%,p<0.005)相比,SCP后pCREB免疫反应性有统计学显著增加(534±60%)。总CREB的测量显示,与假手术动物相比,SCP确实诱导了CREB的统计学显著增加(168±31%,p<0.05)。
与深低温停循环相比,SCP改善了皮质氧合,并阻止了细胞外多巴胺和羟自由基的增加。SCP后纹状体中pCREB的增加可能有助于该操作后细胞恢复的改善。