脑死亡供体的血流动力学维持会影响移植器官的质量,包括肠道.尽管去甲肾上腺素(NE)和多巴胺(DA)通常用于维持人类的平均动脉压,在维持脑死亡供体期间,没有标准化的使用方案。我们的目的是比较每种药物的效果,在使用大鼠脑死亡捐赠模型的肠移植物质量中。
Wistar大鼠(N=17)接受NE(NE组)或DA(DA组)给药2小时的脑死亡(BD);对照组机械通气2小时,无BD。在维持期结束时获得空肠活检。使用Park-Chiu量表评估组织学损伤。绒毛/隐窝比率,粘膜厚度,杯状细胞计数,和绒毛密度使用ImageJ软件(美国国立卫生研究院,贝塞斯达,MD)。通过对肝脏样品进行细菌移位培养计数来评估屏障损伤。通过免疫组织化学和白细胞介素(IL)-6,IL-22和CXCL10的基因表达分析,通过CD3计数评估肠道的炎症状态。
与DA治疗的供体相比,去甲肾上腺素治疗的供体在肠粘膜中具有更高的局灶性缺血性损伤,而形态计量学参数没有实质性改变。从脑死亡供体获得的肠道中CD3+粘膜浸润更大,NE中最高(p=0.001)。BD:DA和NE组的局部炎症介质受到影响,显示出IL-22表达降低的趋势,而NE组的CXCL10表达高于对照组。脑死亡促进肠道细菌易位,但使用NE导致肝脏中细菌计数最高(p<0.01)。
我们的结果支持使用DA代替NE作为主要的血管活性药物来控制BD相关的血流动力学不稳定。多巴胺可能有助于改善肠道移植物的质量,通过更好地保持屏障功能和降低免疫细胞浸润。
背景:脑死亡供体的血流动力学维持会影响移植器官的质量,包括肠道.尽管去甲肾上腺素(NE)和多巴胺(DA)通常用于维持人类的平均动脉压,在维持脑死亡供体期间,没有标准化的使用方案。我们的目的是比较每种药物的效果,在使用大鼠脑死亡捐赠模型的肠移植物质量中。
方法:Wistar大鼠(N=17)脑死亡(BD)2小时,给予NE(NE组)或DA(DA组);对照组机械通气2小时,无BD。在维持期结束时获得空肠活检。使用Park-Chiu量表评估组织学损伤。绒毛/隐窝比率,粘膜厚度,杯状细胞计数,和绒毛密度使用ImageJ软件(美国国立卫生研究院,贝塞斯达,MD)。通过对肝脏样品进行细菌移位培养计数来评估屏障损伤。通过免疫组织化学和白细胞介素(IL)-6,IL-22和CXCL10的基因表达分析,通过CD3计数评估肠道的炎症状态。
结果:与DA治疗的供体相比,去甲肾上腺素治疗的供体在肠粘膜中具有更高的局灶性缺血性损伤,而形态参数没有实质性改变。从脑死亡供体获得的肠道中CD3+粘膜浸润更大,NE中最高(p=0.001)。BD:DA和NE组的局部炎症介质受到影响,显示出IL-22表达降低的趋势,而NE组的CXCL10表达高于对照组。脑死亡促进肠道细菌易位,但使用NE导致肝脏中细菌计数最高(p<0.01)。
结论:我们的结果支持使用DA代替NE作为主要的血管活性药物来控制BD相关的血流动力学不稳定。多巴胺可能有助于改善肠道移植物的质量,通过更好地保持屏障功能和降低免疫细胞浸润。
The hemodynamic maintenance of brain-dead donors will influence the quality of the organs procured for transplantation, including the intestine. Although norepinephrine (NE) and dopamine (DA) are commonly used to sustain mean arterial pressure in humans, there are no standardized protocols for their use during maintenance of brain-dead donors. Our aim was to compare the effects of each drug, in the intestinal graft quality using a rat brain-dead donation model.
Wistar rats (N = 17) underwent brain death (BD) for 2 hours with NE (NE group) or with DA (DA group) administration; the control group was mechanically ventilated for 2 hours without BD. Jejunum biopsies were obtained at the end of the maintenance period. Histological damage was evaluated using Park-Chiu scale. Villi/crypt ratio, mucosal thickness, Goblet cell count, and villi density were evaluated using ImageJ software (US National Institutes of Health, Bethesda, MD). Barrier damage was assessed by bacterial translocation culture counting on liver samples. The inflammatory status of the intestine was evaluated by CD3+ counting by immunohistochemistry and gene expression analysis of interleukin (IL)-6, IL-22, and CXCL10.
Norepinephrine-treated donors had higher focal ischemic injury in the intestinal mucosa without a substantial modification of morphometrical parameters compared with DA-treated donors. CD3+ mucosal infiltration was greater in intestines procured from brain-dead donors, being highest in NE (p ˂ 0.001). Local inflammatory mediators were affected in BD: DA and NE groups showed a trend to lower expression of IL-22, whereas CXCL10 expression was higher in NE versus control group. Brain death promoted intestinal bacterial translocation, but the use of NE resulted in the highest bacterial counting in the liver (p ˂ 0.01).
Our results favor the use of DA instead of NE as main vasoactive drug to manage BD-associated hemodynamic instability. Dopamine may contribute to improve the quality of the intestinal graft, by better preserving barrier function and lowering immune cell infiltration.
BACKGROUND: The hemodynamic maintenance of brain-dead donors will influence the quality of the organs procured for transplantation, including the intestine. Although norepinephrine (NE) and dopamine (DA) are commonly used to sustain mean arterial pressure in humans, there are no standardized protocols for their use during maintenance of brain-dead donors. Our aim was to compare the effects of each drug, in the intestinal graft quality using a rat brain-dead donation model.
METHODS: Wistar rats (N = 17) underwent brain death (BD) for 2 hours with NE (NE group) or with DA (DA group) administration; the control group was mechanically ventilated for 2 hours without BD. Jejunum biopsies were obtained at the end of the maintenance period. Histological damage was evaluated using Park-Chiu scale. Villi/crypt ratio, mucosal thickness, Goblet cell count, and villi density were evaluated using ImageJ software (US National Institutes of Health, Bethesda, MD). Barrier damage was assessed by bacterial translocation culture counting on liver samples. The inflammatory status of the intestine was evaluated by CD3 + counting by immunohistochemistry and gene expression analysis of interleukin (IL)-6, IL-22, and CXCL10.
RESULTS: Norepinephrine-treated donors had higher focal ischemic injury in the intestinal mucosa without a substantial modification of morphometrical parameters compared with DA-treated donors. CD3 + mucosal infiltration was greater in intestines procured from brain-dead donors, being highest in NE ( p ˂ 0.001). Local inflammatory mediators were affected in BD: DA and NE groups showed a trend to lower expression of IL-22, whereas CXCL10 expression was higher in NE versus control group. Brain death promoted intestinal bacterial translocation, but the use of NE resulted in the highest bacterial counting in the liver ( p ˂ 0.01).
CONCLUSIONS: Our results favor the use of DA instead of NE as main vasoactive drug to manage BD-associated hemodynamic instability. Dopamine may contribute to improve the quality of the intestinal graft, by better preserving barrier function and lowering immune cell infiltration.