Lactic Acidosis as a Result of Iron Deficiency

A B S T R A C T Iroin-deficien1t rats halve an1 im11paired work performancice, even when their aniemiiia is correcte(d by exchanige transfusioin. Muscle activity is associate(l with a higher blood lactate concenltrationi thani is observed in iron-replete aniimals. The accumulation of lactate is a result of excessive productioni as lactate clearancie fromn the 1)loo0( was shown to be unaffecte(l. By acljusting the work loa(l to a lower level, it was possible to (livide iron-deficient animilals into two groups, oine capal)le of continued treadlmiill runninig and aniother in which aniimals stoppe(d before 20( min. In the former, blood lactate conicenitrationi reache(d a plateau at moderate levels, whereas it coontiniued to increase in the latter until the anIimial stopped runninig. Levels ofa-glycerophosphate oxidase in skeletal mulscle mitochondria were found( to be mulch lower in the secon(d group (P < 0.001). Lactate infusioin into normiial animals was showin to interfere with work performiiance, anid muainteinance of a normiial pH in iron-deficieint anid iron-replete animiials didinot prevent the impairment in work associated with high bloo(1 lactate concentrations. Additional evidenlce Wcas obtained that energy substrate (blood glucose anid free fatty acids, muscle glycogen) was adequate in irondeficient animiials. Oxygein tension in their vena caval blood was higher than in controls. Fuirthermore, the in situ behavior of electrically stimulated gastrocnemius and soleus muscles appeared similar to that of control animals. Because the stimulation of the single muscle in the iron-deficient animal did not result in appreciable elevation of blood lactate andl did not show impaired contractility further supported the hypothesis that the elevation ofblood lactate caused the decreased work performance. It is concluded that iron deficiency by a depletion in the iron-containing mitochondrial enzyme, a-glycerophosphate oxidase,