Effect of chloramphenicol on mitochondrial and extramitochondrial systems in the isolated perfused rat heart

The isolated, perfused working rat heart was used as a model for investigating the effects of chloramphenicol on mitochondrial amino acid incorporation in an intact organ. The most obvious inhibitory effects of chloramphenicol were extramitochondrial: decreased mechanical performance of the heart and marked reduction in glucose uptake and lactate production. The ATP levels of the perfused heart were significantly increased at high levels of chloramphenicol. Chloramphenicol (50 to 500 μg/ml perfusate) did not inhibit the incorporation into the mitochondria or other subcellular fractions. A specific inhibitory effect on mitochondrial protein synthesis could only be observed when the cytoplasmic protein synthetizing system had been inhibited by cycloheximide. Under these conditions it could be demonstrated that the chloramphenicol sensitivity was greater for the synthesis of the insoluble proteins than for that of the soluble proteins of the mitochondria The chloramphenicol inhibition of mitochondrial protein synthesis which could be obtained in the isolated heart was approx. 70% which was twice as high as could be achieved when isolated mitochondria were incorporating amino acids.