Acute Myocardial Effects of Chloramphenicol in Newborn Pigs: A Possible Insight into the Gray Baby Syndrome

• Published in: The Journal of infectious diseases Vol. 152; no. 2; pp. 344 - 350
• Main Authors: Werner, John C., Whitman, Victor, Schuler, H. Gregg, Fripp, Raymond R., Rannels, Anne M., Kasales, Claudia J., LaNoue, Kathryn F.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01-08-1985; University of Chicago Press
• Subjects: Animals; Animals, Newborn; Antibiotics; Biological and medical sciences; Blood Pressure - drug effects; Cardiac Output - drug effects; Chloramphenicol - toxicity; Cyanosis - chemically induced; Drug toxicity and drugs side effects treatment; Enzymes; Esters; Heart; Heart - drug effects; Heart mitochondria; Humans; In Vitro Techniques; Infant, Newborn; Ketoglutaric Acids - metabolism; Medical sciences; Mitochondria; Mitochondria, Heart - drug effects; Mitochondria, Heart - metabolism; Original Articles; Oxidation; Perfusion; Pharmacology. Drug treatments; Respiration; Shock - chemically induced; Succinates - metabolism; Succinic Acid; Swine; Syndrome; Toxicity: cardiovascular system; Vertebrata; Antibiotic; Mammalia; Toxicity; Newborn animal; Myocardium; Cardiovascular disease; Chloramphenicol; Artiodactyla; Ungulata; Pig
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/152.2.344

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 µg/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 µg/ml) on oxidative activity of isolated mitochondria were also investigated. With unesterified chloramphenicol, inhibition of state 3 respiration was most apparent when glutamate and palmity1carnitine were supplied as substrates. Inhibition of mitochondrial oxidation of succinate or glutamate was only detectable at 200 µg/ml. Inhibition of α-ketoglutarate oxidation was not seen at any concentration of antibiotic studied. Chloramphenicol succinate most strongly inhibited state 3 oxidation of succinate and α-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.