Hyperlactataemia, hyperkalemia and heart block in acute iron overload: the fatal role of the hepatic iron-incorporation rate in rats on ferric citrate infusions.
An animal model is presented that provides constant and controllable conditions for approaching gradually, and within reasonable time, different stages of iron overload and, probably, an iron-induced mitochondrial disorder. Thirty-five rats were infused with ferric citrate, sodium citrate and saline at constant rates for 6-24 h. In the 200-3200 micrograms Fe h-1 loading range, the iron-incorporation capacity of the liver was not saturable and the fractional iron uptake by the liver remained at approximately 30% even at a loading rate of 3200 micrograms Fe h-1. Up to a loading rate of 200 micrograms Fe h-1, iron storage was not associated with toxic effects. Beyond this loading rate, however, the liver was no longer able to prevent a massive plasma iron increase on one side and hyperlactataemia on the other. These signs most probably represent hepatocellular decompensation with respect to a critical iron-storage rate. The product of plasma iron x exposition time was significantly correlated with increased plasma lactate levels (r = 0.89, P less than 0.005), whereas increased plasma iron levels per se were not. Hyperlactataemia was associated with hyperkalaemia and progressive cardiac conduction defects leading to cardiac arrest at lactate concentration of 9.1 +/- 4.3 mmol l-1. The hypothesis is discussed that toxicity in acute iron overload may entirely be due to hepatocellular (mitochondrial) damage, and not to multiple organ iron overload.
D000818:Animals; D004195:Disease Models, Animal; D004562:Electrocardiography; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity; D006327:Heart Block / Q000097:blood / Q000139:chemically induced* / Q000401:mortality; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006947:Hyperkalemia / Q000097:blood / Q000139:chemically induced* / Q000401:mortality; D007262:Infusions, Intravenous; D007501:Iron / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D007773:Lactates / Q000009:adverse effects / Q000097:blood*; D019344:Lactic Acid; D008099:Liver / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D005290:Ferric Compounds; D007773:Lactates; D019344:Lactic Acid; C025314:ferric citrate; D007501:Iron