Recovery of endothelial function in severe falciparum malaria: relationship with improvement in plasma L-arginine and blood lactate concentrations.
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 fa...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2008
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| _version_ | 1826276453008801792 |
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| author | Yeo, T Lampah, D Gitawati, R Tjitra, E Kenangalem, E McNeil, Y Darcy, C Granger, D Weinberg, J Lopansri, B Price, R Duffull, S Celermajer, D Anstey, N |
| author_facet | Yeo, T Lampah, D Gitawati, R Tjitra, E Kenangalem, E McNeil, Y Darcy, C Granger, D Weinberg, J Lopansri, B Price, R Duffull, S Celermajer, D Anstey, N |
| author_sort | Yeo, T |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T23:14:11Z |
| format | Journal article |
| id | oxford-uuid:6688329a-9ba2-4ddc-83cf-5422e1d38020 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:14:11Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:6688329a-9ba2-4ddc-83cf-5422e1d380202022-03-26T18:32:35ZRecovery of endothelial function in severe falciparum malaria: relationship with improvement in plasma L-arginine and blood lactate concentrations.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6688329a-9ba2-4ddc-83cf-5422e1d38020EnglishSymplectic Elements at Oxford2008Yeo, TLampah, DGitawati, RTjitra, EKenangalem, EMcNeil, YDarcy, CGranger, DWeinberg, JLopansri, BPrice, RDuffull, SCelermajer, DAnstey, NBACKGROUND: 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. |
| spellingShingle | Yeo, T Lampah, D Gitawati, R Tjitra, E Kenangalem, E McNeil, Y Darcy, C Granger, D Weinberg, J Lopansri, B Price, R Duffull, S Celermajer, D Anstey, N Recovery of endothelial function in severe falciparum malaria: relationship with improvement in plasma L-arginine and blood lactate concentrations. |
| title | Recovery of endothelial function in severe falciparum malaria: relationship with improvement in plasma L-arginine and blood lactate concentrations. |
| title_full | Recovery of endothelial function in severe falciparum malaria: relationship with improvement in plasma L-arginine and blood lactate concentrations. |
| title_fullStr | Recovery of endothelial function in severe falciparum malaria: relationship with improvement in plasma L-arginine and blood lactate concentrations. |
| title_full_unstemmed | Recovery of endothelial function in severe falciparum malaria: relationship with improvement in plasma L-arginine and blood lactate concentrations. |
| title_short | Recovery of endothelial function in severe falciparum malaria: relationship with improvement in plasma L-arginine and blood lactate concentrations. |
| title_sort | recovery of endothelial function in severe falciparum malaria relationship with improvement in plasma l arginine and blood lactate concentrations |
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