Relationship of cell-free hemoglobin to impaired endothelial nitric oxide bioavailability and perfusion in severe falciparum malaria
TW Yeo, DA Lampah, E Tjitra, R Gitawati… - The Journal of …, 2009 - academic.oup.com
TW Yeo, DA Lampah, E Tjitra, R Gitawati, E Kenangalem, K Piera, DL Granger, BK Lopansri…
The Journal of infectious diseases, 2009•academic.oup.comBackground Hemolysis causes anemia in falciparum malaria, but its contribution to
microvascular pathology in severe malaria (SM) is not well characterized. In other hemolytic
diseases, release of cell-free hemoglobin causes nitric oxide (NO) quenching, endothelial
activation, and vascular complications. We examined the relationship of plasma hemoglobin
and myoglobin to endothelial dysfunction and disease severity in malaria Methods Cell-free
hemoglobin (a potent NO quencher), reactive hyperemia peripheral arterial tonometry (RH …
microvascular pathology in severe malaria (SM) is not well characterized. In other hemolytic
diseases, release of cell-free hemoglobin causes nitric oxide (NO) quenching, endothelial
activation, and vascular complications. We examined the relationship of plasma hemoglobin
and myoglobin to endothelial dysfunction and disease severity in malaria Methods Cell-free
hemoglobin (a potent NO quencher), reactive hyperemia peripheral arterial tonometry (RH …
Abstract
BackgroundHemolysis causes anemia in falciparum malaria, but its contribution to microvascular pathology in severe malaria (SM) is not well characterized. In other hemolytic diseases, release of cell-free hemoglobin causes nitric oxide (NO) quenching, endothelial activation, and vascular complications. We examined the relationship of plasma hemoglobin and myoglobin to endothelial dysfunction and disease severity in malaria
MethodsCell-free hemoglobin (a potent NO quencher), reactive hyperemia peripheral arterial tonometry (RH-PAT) (a measure of endothelial NO bioavailability), and measures of perfusion and endothelial activation were quantified in adults with moderately severe (n=78) or severe (n=49) malaria and control subjects (n=16) from Papua, Indonesia
ResultsCell-free hemoglobin concentrations in patients with SM (median, 5.4 μmol/L; interquartile range [IQR], 3.2–7.4 μmol/L) were significantly higher than in those with moderately severe malaria (2.6 μmol/L; IQR, 1.3–4.5 μmol/L) or controls (1.2 μmol/L; IQR, 0.9–2.4 μmol/L; P<.001). Multivariable regression analysis revealed that cell-free hemoglobin remained inversely associated with RH-PAT, and in patients with SM, there was a significant longitudinal association between improvement in RH-PAT index and decreasing levels of cell-free hemoglobin (P=.047). Cell-free hemoglobin levels were also independently associated with lactate, endothelial activation, and proinflammatory cytokinemia
ConclusionsHemolysis in falciparum malaria results in NO quenching by cell-free hemoglobin, and may exacerbate endothelial dysfunction, adhesion receptor expression and impaired tissue perfusion. Treatments that increase NO bioavailability may have potential as adjunctive therapies in SM
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