Acute myocardial effects of chloramphenicol in newborn pigs: a possible insight into the gray baby syndrome.
Mechanical function and mitochondrial respiration were observed in newborn pig hearts in the presence of chloramphenicol. Isolated perfused hearts exposed to chloramphenicol (25, 50, or 100 micrograms/ml) demonstrated acute reductions in pressure development and cardiac output accompanied by elevated left atrial filling pressure. The effects of chloramphenicol and chloramphenicol succinate (25, 50, 100, or 200 micrograms/ml) on oxidative activity of isolated mitochondria were also investigated. With unesterified chloramphenicol, inhibition of state 3 respiration was most apparent when glutamate and palmitylcarnitine were supplied as substrates. Inhibition of mitochondrial oxidation of succinate or glutamate was only detectable at 200 micrograms/ml. Inhibition of alpha-ketoglutarate oxidation was not seen at any concentration of antibiotic studied. Chloramphenicol succinate most strongly inhibited state 3 oxidation of succinate and alpha-ketoglutarate and had relatively mild effects on oxidation of glutamate and palmitylcarnitine. Succinate oxidation by submitochondrial particles was unaffected by chloramphenicol succinate, a result suggesting interference with succinate transport.
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002701:Chloramphenicol / Q000633:toxicity*; D003490:Cyanosis / Q000139:chemically induced*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007656:Ketoglutaric Acids / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D010477:Perfusion; D012769:Shock / Q000139:chemically induced*; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid; D013552:Swine; D013577:Syndrome
D007656:Ketoglutaric Acids; D013386:Succinates; D002701:Chloramphenicol; D019802:Succinic Acid