Does Beta Blockade Postinjury Prevent Bone Marrow Suppression?
Does Beta Blockade Postinjury Prevent Bone Marrow Suppression?
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DOI：
10.1097/ta.0b013e3182169326
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发表时间：
2011-05-01
影响因子：
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通讯作者：
Livingston, David H.
中科院分区：
文献类型：
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作者：
Mohr, Alicia M.;ElHassan, Ihab O.;Livingston, David H.
背景资料：创伤诱导的高儿茶酚胺血症通过抑制骨髓造血祖细胞（HPC）生长和增加HPC向损伤组织的流出而对骨髓（BM）功能产生负面影响。在组织损伤前单独给予β阻断剂（BB）已显示可减少HPC动员并恢复BM内的HPC集落生长。在一个临床相关的模型，本研究探讨了组织损伤和出血性休克（HS）后给予BB的效果。方法：雄性Sprague-Dawley大鼠肺挫伤（LC）与冲击波冲击。LC后通过维持平均动脉血压30 mm Hg至35 mm Hg 45 min实现HS。一旦平均动脉血压> 80 mm Hg，给予普萘洛尔（10 mg/kg），随后每天给药（LC/HS/BB）。伤后1天和7天，分析骨髓和肺组织中HPC的生长、血液学参数和肺损伤的组织学。LC/HS显著抑制BM CFU-E生长（15 +/- 8对比35 +/- 2），并且当与1天和7天时的LC相比时，增加了损伤组织中的CFU-E生长（33 +/- 5对比22 +/- 9）。在LC/HS后使用BB改善了伤后1天和7天的BM抑制、贫血程度和损伤肺中的HPC生长。肺损伤评分显示，使用BB时肺愈合没有恶化（LC/HS/BB 3.2 +/- 2 vs. LC/HS 3.8 +/- 0.8）。结论：在损伤和休克模型中，复苏后立即给予普萘洛尔显著降低BM抑制，并且每天使用BB时保护作用维持在7天。虽然BB似乎通过减少HPC向损伤组织的动员来改善BM功能，但肺愈合没有恶化。因此，在创伤和复苏后使用普萘洛尔可以最大限度地减少损伤后的长期BM抑制，对愈合无不良影响。
Background: Trauma-induced hypercatecholaminemia negatively impacts bone marrow (BM) function by suppressing BM hematopoietic progenitor cell (HPC) growth and increasing HPC egress to injured tissue. Beta blockade (BB) given before tissue injury alone has been shown to reduce both HPC mobilization and restore HPC colony growth within the BM. In a clinically relevant model, this study examines the effect of BB given after both tissue injury and hemorrhagic shock (HS).Methods: Male Sprague-Dawley rats underwent lung contusion (LC) with a blast wave percussion. HS was achieved after LC by maintaining the mean arterial blood pressure 30 mm Hg to 35 mm Hg for 45 minutes. Propranolol (10 mg/kg) was given once the mean arterial blood pressure > 80 mm Hg and subsequent doses were given daily (LC/HS/BB). One-day and 7-day postinjury, analysis of BM and lung tissue for the growth of HPCs, hematologic parameters, and histology of lung injury were performed.Results: LC/HS significantly worsens BM CFU-E growth suppression (15 +/- 8 vs. 35 +/- 2) and increases CFU-E growth in injured tissue when compared with LC at 1 day and 7 days (33 +/- 5 vs. 22 +/- 9). The use of BB after LC/HS ameliorated BM suppression, the degree of anemia and HPC growth in the injured lung at 1 day and 7 days postinjury. Lung injury score shows that there was no worsening of lung healing with BB (LC/HS/BB 3.2 +/- 2 vs. LC/HS 3.8 +/- 0.8).Conclusion: In an injury and shock model, administration of propranolol immediately after resuscitation significantly reduced BM suppression, and the protective effect is maintained at 7 days with daily BB. Although BB appears to improve BM function by decreasing HPC mobilization to injured tissue, there was no worsening of lung healing. Therefore, the use of propranolol after trauma and resuscitation may minimize long-term BM suppression after injury with no adverse impact on healing.