title: Recovery of endothelial function in severe falciparum malaria: relationship with improvement in plasma L-arginine and blood lactate concentrations.
abstract: 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.
authors.affiliation: International Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia.
authors.forename: Tsin W
authors.initials: TW
authors.lastname: Yeo
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Lampah
authors.forename: Retno
authors.initials: R
authors.lastname: Gitawati
authors.forename: Emiliana
authors.initials: E
authors.lastname: Tjitra
authors.forename: Enny
authors.initials: E
authors.lastname: Kenangalem
authors.forename: Yvette R
authors.initials: YR
authors.lastname: McNeil
authors.forename: Christabelle J
authors.initials: CJ
authors.lastname: Darcy
authors.forename: Donald L
authors.initials: DL
authors.lastname: Granger
authors.forename: J Brice
authors.initials: JB
authors.lastname: Weinberg
authors.forename: Bert K
authors.initials: BK
authors.lastname: Lopansri
authors.forename: Ric N
authors.initials: RN
authors.lastname: Price
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Duffull
authors.forename: David S
authors.initials: DS
authors.lastname: Celermajer
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Anstey
mesh_terms: D000138:Acidosis / Q000097:blood / Q000469:parasitology / Q000473:pathology*; D000328:Adult; D001120:Arginine / Q000097:blood / Q000502:physiology*; D001682:Biological Availability; D004730:Endothelium, Vascular / Q000502:physiology* / Q000503:physiopathology; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D016778:Malaria, Falciparum / Q000473:pathology* / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D010949:Plasma; D020127:Recovery of Function
chemical_list: D009569:Nitric Oxide; D019344:Lactic Acid; D001120:Arginine