Metformin overdose, but not lactic acidosis per se, inhibits oxygen consumption in pigs.

Critical Care : the Official Journal of the Critical Care Forum
Alessandro ProttiLuciano Gattinoni

Abstract

Hepatic mitochondrial dysfunction may play a critical role in the pathogenesis of metformin-induced lactic acidosis. However, patients with severe metformin intoxication may have a 30 to 60% decrease in their global oxygen consumption, as for generalized inhibition of mitochondrial respiration. We developed a pig model of severe metformin intoxication to validate this clinical finding and assess mitochondrial function in liver and other tissues. Twenty healthy pigs were sedated and mechanically ventilated. Ten were infused with a large dose of metformin (4 to 8 g) and five were not (sham controls). Five others were infused with lactic acid to clarify whether lactic acidosis per se diminishes global oxygen use. Arterial pH, lactatemia, global oxygen consumption (VO2) (metabolic module) and delivery (DO2) (cardiac output by thermodilution) were monitored for nine hours. Oxygen extraction was computed as VO2/DO2. Activities of the main components of the mitochondrial respiratory chain (complex I, II and III, and IV) were measured with spectrophotometry (and expressed relative to citrate synthase activity) in heart, kidney, liver, skeletal muscle and platelets taken at the end of the study. Pigs infused with metformin (6 ± 2 g; fin...Continue Reading

Citations

Nov 1, 2013·The New England Journal of Medicine·Kamyar Kalantar-Zadeh
Jul 26, 2012·Critical Care : the Official Journal of the Critical Care Forum·George TsaknisApostolos Armaganidis
Oct 5, 2012·Critical Care : the Official Journal of the Critical Care Forum·Alessandro ProttiLuciano Gattinoni
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