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Tsin W. Yeo, Daniel A. Lampah, Retno Gitawati, Emiliana Tjitra, Enny Kenangalem, Yvette R. McNeil, Christabelle J. Darcy, Donald L. Granger, J. Brice Weinberg, Bert K. Lopansri, Ric N. Price, Stephen B. Duffull, David S. Celermajer, Nicholas M. Anstey, Recovery of Endothelial Function in Severe Falciparum Malaria: Relationship with Improvement in Plasma l-Arginine and Blood Lactate Concentrations, The Journal of Infectious Diseases, Volume 198, Issue 4, 15 August 2008, Pages 602–608, https://doi.org/10.1086/590209
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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 µmol/L/24 h (95% confidence interval [CI], 9–13 µmol/L/24 h), from a baseline of 49 µmol/L (95% CI, 37–45 µmol/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.
