Recovery of endothelial function in severe falciparum malaria: Relationship with improvement in plasma L-arginine and blood lactate concentrations
Recovery of endothelial function in severe falciparum malaria: Relationship with improvement in plasma L-arginine and blood lactate concentrations
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DOI：
10.1086/590209
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发表时间：
2008-08-15
影响因子：
6.4
通讯作者：
Anstey, Nicholas M.
中科院分区：
文献类型：
--
作者：
Yeo, Tsin W.;Lampah, Daniel A.;Anstey, Nicholas M.
背景。严重疟疾的特点是微血管阻塞、内皮功能障碍以及l -精氨酸和一氧化氮（NO）水平降低。l -精氨酸输注改善中重度疟疾患者的内皮功能。在重症疟疾中，内皮功能障碍的纵向病程和与康复相关的因素均未被确定。采用反应性充血外周动脉血压计（RH-PAT），对印度尼西亚患有严重疟疾（n = 49）或中度疟疾（n = 48）的成人进行了内皮功能纵向测量。在混合效应模型中，重型疟疾患者RH-PAT指数的变化与寄生虫血症、乳酸、酸中毒和血浆l -精氨酸浓度的变化有关。重症疟疾患者出院或死亡前内皮功能障碍比例由94%（46/49例）降至14%（6/42例）（P < 0.001）。在严重疟疾患者中，抗疟治疗开始后内皮功能恢复正常的中位时间为49小时（四分位数范围为20-70小时）。重症疟疾患者L-精氨酸浓度平均增加11 μ mol/L/24 h(95%可信区间[CI]， 9-13 μ mol/L/24 h)，高于基线49 μ mol/L （95% CI, 37-45 μ mol/L）。重症疟疾患者内皮功能的改善与l -精氨酸水平升高（r = 0.56; P = 0.008）和乳酸水平降低（r = -0.44; P = 0.001）相关。严重疟疾患者内皮功能的恢复与低精氨酸血症和乳酸酸中毒的恢复有关。能够改善内皮NO生成和内皮功能的药物，如l -精氨酸，可能有潜力在重症疟疾病程早期作为辅助治疗。
Background. Severe malaria is characterized by microvascular obstruction, endothelial dysfunction, and reduced levels of L-arginine and nitric oxide (NO). L-Arginine infusion improves endothelial function in moderately severe malaria. Neither the longitudinal course of endothelial dysfunction nor factors associated with recovery have been characterized in severe malaria.Methods. Endothelial function was measured longitudinally in adults with severe malaria (n = 49) or moderately severe malaria (n = 48) in Indonesia, using reactive hyperemia peripheral arterial tonometry (RH-PAT). In a mixed-effects model, changes in RH-PAT index values in patients with severe malaria were related to changes in parasitemia, lactate, acidosis, and plasma L-arginine concentrations.Results. Among patients with severe malaria, the proportion with endothelial dysfunction fell from 94% (46/49 patients) to 14% (6/42 patients) before discharge or death (P < .001). In severe malaria, the median time to normal endothelial function was 49 h (interquartile range, 20-70 h) after the start of antimalarial therapy. The mean increase in L-arginine concentrations in patients with severe malaria was 11 mu mol/L/24 h (95% confidence interval [CI], 9-13 mu mol/L/24 h), from a baseline of 49 mu mol/L (95% CI, 37-45 mu mol/L). Improvement of endothelial function in patients with severe malaria correlated with increasing levels of L-arginine (r = 0.56; P = .008) and decreasing levels of lactate (r = -0.44; P = .001).Conclusions. Recovery of endothelial function in severe malaria is associated with recovery from hypoargininemia and lactic acidosis. Agents that can improve endothelial NO production and endothelial function, such as L-arginine, may have potential as adjunctive therapy early during the course of severe malaria.