The link between increased lactate production and mortality in pneumonia
A recent study established increased lactate levels as a predictor for mortality from pneumonia. X-ray abnormalities were increased in patients with elevated lactate levels (1). Recent work established that prophylactic specific inhibition of nitric oxide production by N- acetylcysteine leads to a reduced lactate production as well as a reduced severity of lung injury in an animal model of sepsis induced lung injury (2). Nitric oxide metabolites like peroxynitrite cause mitochondrial dysfunction by nitrosylation of key enzymes. The effect of inhibition of nitric oxide production could be explained by preservation of mitochondrial function. A recent study established the key role of mitochondrial function in amelioration of lung injury (3).Mitochondrial dysfunction leads to cellular depletion of ATP increasing lactate generation by anaerobic metabolism. Intracellular ATP depletion leads to reversible dysfunction of the ATP dependent sodium potassium ATPase at the basolateral cell membrane which generates the sodium gradient essential for pulmonary fluid clearance (4, 5). The authors indicated that they were not sure what the response to a high lactate level in patients with pneumonia should be. A response which should be explored by future investigations is inhibition of nitric oxide production by N-acetylcysteine. References: 1. Ramakrishna B, Graham SM Phiri A, Mankhambo L, Duke T. Lactate as a predictor of mortality in Malawian children with WHO-defined pneumonia. Arch Dis Child 2012;97:336-342. 2. Campos R, Shimizu MHM, Volpini RA, De Braganca AC, Andrade L, Dos Santos Lopes FDTQ, Olivo C, Canale D, Seguro AC. N-acetylcysteine prevents pulmonary edema and acute kidney injury in rats with sepsis submitted to mechanical ventilation. Am J Physiol Lung Cell Mol Physiol 2012;302:L640- L650. 3. Islam MN, Das SR, Emin MT, Wei M, Sun L, Westphalen K, Rowlands DJ, Quadri SK, Bhattacharya S, Bhattacharya J. Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nature Medicine 2012; 18:759-765 4. Ikenouchi H,Zhao L, McMillan M, Hammond EM, Barry WH.ATP depletion causes a reversible decrease in Na+ pump density in cultured ventricular myocytes. Am J Physiol 1993;264:1208-1214. 5. Factor P. Role and regulation of lung Na,K-ATPase. Cell Mol Biol 2001; 47:347-361.
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