Niebauer J, Volk H D, Kemp M, Dominguez M, Schumann R R, Rauchhaus M, Poole-Wilson P A, Coats A J, Anker S D
Cardiac Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
Lancet. 1999 May 29;353(9167):1838-42. doi: 10.1016/S0140-6736(98)09286-1.
Immune activation in patients with chronic heart failure may be secondary to endotoxin (lipopolysaccharide) action. We investigated the hypothesis that altered gut permeability with bacterial translocation and endotoxaemia would be increased in patients with oedema secondary to congestive heart failure.
We compared 20 patients who had chronic heart failure with recent-onset peripheral oedema (mean age 64 years [SD 10], New York Heart Association [NYHA] class 3.3 [0.7]), 20 stable non-oedematous patients with chronic heart failure (mean age 63 years [19], NYHA class 2.6 [0.7]), and 14 healthy volunteers (mean age 55 years [16]). Biochemical markers of endotoxaemia, inflammation, and immune activation were measured. Ten patients were studied within 1 week of complete resolution of oedema. Five patients survived longer than 6 months and were restudied again after remaining free of oedema for more than 3 months.
Mean endotoxin concentrations were higher in oedematous patients with chronic heart failure than in stable patients with chronic heart failure (0.74 [SD 0.45] vs 0.37 EU/mL [0.23], p=0.0009) and controls (0.46 EU/mL [0.21], p=0.02). Oedematous patients had the highest concentrations of several cytokines. After short-term diuretic treatment, endotoxin concentrations decreased from 0.84 EU/mL [0.49] to 0.45 EU/mL [0.21], p<0.05) but cytokines remained raised. After freedom of oedema for more than 3 months after oedema resolved, endotoxin concentrations remained unchanged from the previous visit (0.49 EU/mL [0.06], p=0.45).
Raised concentrations of endotoxin and cytokines are found in patients with chronic heart failure during acute oedematous exacerbation. Intensified diuretic treatment can normalise endotoxin concentrations. Our preliminary findings suggest that endotoxin may trigger immune activation in patients with chronic heart failure during oedematous episodes.
慢性心力衰竭患者的免疫激活可能继发于内毒素（脂多糖）作用。我们研究了这样一个假设，即充血性心力衰竭继发水肿的患者，其肠道通透性改变伴细菌移位和内毒素血症会增加。
我们比较了20例近期出现外周水肿的慢性心力衰竭患者（平均年龄64岁[标准差10]，纽约心脏协会[NYHA]心功能分级3.3级[0.7]）、20例稳定的无水肿慢性心力衰竭患者（平均年龄63岁[19]，NYHA心功能分级2.6级[0.7]）和14名健康志愿者（平均年龄55岁[16]）。测量了内毒素血症、炎症和免疫激活的生化标志物。10例患者在水肿完全消退后1周内接受研究。5例患者存活超过6个月，在无水肿超过3个月后再次接受研究。
慢性心力衰竭水肿患者的平均内毒素浓度高于稳定的慢性心力衰竭患者（0.74[标准差0.45]对0.37 EU/mL[0.23]，p = 0.0009）和对照组（0.46 EU/mL[0.21]，p = 0.02）。水肿患者的几种细胞因子浓度最高。短期利尿剂治疗后，内毒素浓度从0.84 EU/mL[0.49]降至0.45 EU/mL[0.21]，p<0.05），但细胞因子仍升高。水肿消退后无水肿超过3个月，内毒素浓度与上次就诊时相比无变化（0.49 EU/mL[0.06]，p = 0.45）。
在慢性心力衰竭急性水肿加重期患者中发现内毒素和细胞因子浓度升高。强化利尿剂治疗可使内毒素浓度恢复正常。我们的初步研究结果表明，内毒素可能在慢性心力衰竭患者水肿发作期间触发免疫激活。
