718 EFFECT OF METHYLENE BLUE ON FIBROBLASTS IN LACTIC ACIDOSIS

Abstract

A girl presented on the 9th day of life with familial lactic acidosis, euglycemia and hepatomegaly; death occurred at day 15. Ratios for plasma lactate: pyruvate (130:1) and B-hydroxy-butyrate: acetoacetate (38:1) were elevated suggesting an imbalance of tissue NAD:NADH. Plasma pyruvate (0.25mM, Norm = <.07mM) and alanine (1.7mM, Norm = < .4mM) were both elevated indicating a defect in pyruvate utilization. Organic acids other than those above were not elevated in urine. Skin fibroblasts produced excess lactic acid in culture. Evolution of ¹⁴-CO₂ (nmoles/mg prot · hr ± S.D.) from 1mM L-1¹⁴C lactate (control = 19.8 ± 9.4), L-1¹⁴C pyruvate (control = 41.1 ± 4.7) or L-U¹⁴C alanine (control = 12.7 ± 4.1) was markedly decreased compared to control cells (< 10%, < 1% and <10% respectively). Thiamine (0.7mM) or lipoic acid (0.01mM) for 1 or 24 hours of preincubation had no effect. Dichloroacetate (50μM) produced a modest increase of lactate utilization (150% increase) in the patient's cells, but the effect of methylene blue on alanine utilization (0.27mM) was dramatic (1200% increase), bringing it within the normal range (7.8-20.5nmoles CO₂/mg prot · hr).

Our findings suggest that methylene blue can repair lactic acidosis in vitro and may be of use in patients whose cellular regeneration of NAD is impaired.

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