Recovery of endothelial function in severe falciparum malaria: relationship with improvement in plasma L-arginine and blood lactate concentrations.

Journal Article (Journal Article)

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 micromol/L/24 h (95% confidence interval [CI], 9-13 micromol/L/24 h), from a baseline of 49 micromol/L (95% CI, 37-45 micromol/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.

Full Text

Duke Authors

Cited Authors

  • Yeo, TW; Lampah, DA; Gitawati, R; Tjitra, E; Kenangalem, E; McNeil, YR; Darcy, CJ; Granger, DL; Weinberg, JB; Lopansri, BK; Price, RN; Duffull, SB; Celermajer, DS; Anstey, NM

Published Date

  • August 15, 2008

Published In

Volume / Issue

  • 198 / 4

Start / End Page

  • 602 - 608

PubMed ID

  • 18605903

Pubmed Central ID

  • PMC2709993

International Standard Serial Number (ISSN)

  • 0022-1899

Digital Object Identifier (DOI)

  • 10.1086/590209


  • eng

Conference Location

  • United States