Increased pulmonary pressures and myocardial wall stress in children with severe malaria.
BACKGROUND
Chronic intravascular hemolysis leads to nitric oxide (NO) depletion and pulmonary hypertension in sickle cell disease. To test whether this pathophysiology occurs in malaria, we examined in Mali 53 children who were admitted to the hospital with severe malaria (excluding cerebral malaria) and 31 age-matched controls.


METHODS
Severity of hemolysis was assessed from plasma levels of free hemoglobin and arginase-1. NO metabolism was assessed by whole-blood nitrite levels and plasma NO consumption. Effects on the cardiovascular system and endothelial function were assessed by using echocardiography to measure peak tricuspid regurgitant jet velocity and by evaluating plasma levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP) and soluble vascular cell adhesion molecule-1.


RESULTS
Children with severe malaria had higher plasma levels of hemoglobin and arginase-1, reduced whole-blood levels of nitrite, and increased NO consumption relative to controls. They also had increased pulmonary arterial pressures (P< .05) with elevated levels of NT-proBNP and soluble vascular cell adhesion molecule-1 (P< .001).


CONCLUSIONS
Children with severe malaria have increased pulmonary pressures and myocardial wall stress. These complications are consistent with NO depletion from intravascular hemolysis, and they indicate that the pathophysiologic cascade from intravascular hemolysis to NO depletion and its cardiopulmonary effects is activated in children with severe malaria.
Janka
Jacqueline J
JJ
Clinical Center (Critical Care Medicine Department) and Pulmonary and Vascular Medicine and Translational Medicine Branches, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Koita
Ousmane A
OA
Traoré
Broulaye
B
Traoré
Josépha M
JM
Mzayek
Fawaz
F
Sachdev
Vandana
V
Wang
Xunde
X
Sanogo
Kassoum
K
Sangaré
Lansana
L
Mendelsohn
Laurel
L
Masur
Henry
H
Kato
Gregory J
GJ
Gladwin
Mark T
MT
Krogstad
Donald J
DJ
D001119:Arginase / Q000097:blood; D016022:Case-Control Studies; D002675:Child, Preschool; D004452:Echocardiography; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006461:Hemolysis; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology*; D008288:Malaria / Q000150:complications* / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D012720:Severity of Illness Index; D014262:Tricuspid Valve Insufficiency / Q000209:etiology*
D006454:Hemoglobins; D009569:Nitric Oxide; D001119:Arginase