Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1972 Aug;51(8):2071–2076. doi: 10.1172/JCI107013

Free fatty acid oxidation and carnitine levels in diphtheritic guinea pig myocardium

David R Challoner 1,2, Hans G Prols 1,2
PMCID: PMC292363  PMID: 5054465

Abstract

Previous studies from this laboratory and by Wittels and Bressler have suggested that myocardial carnitine depletion and an accompanying decrease in fatty acid oxidation may contribute to the myocardial disease associated with diphtheria. In addition, administration of carnitine was found to prolong survival of diphtheritic guinea pigs and improve ventricular function in diphtheritic dogs.

The present studies document the hypothesis that the defect in myocardial carnitine, directly assayed, could be repleted in diphtheritic guinea pigs to whom carnitine was administered intraperitoneally. The decreased fatty acid oxidation previously reported only for homogenates was confirmed in an isolated perfused diphtheritic guinea pig heart preparation. The addition of L-carnitine to this perfusate augmented fatty acid oxidation to normal levels.

Taken together, these and previous studies would support a pathogenetic role for carnitine depletion in diphtheritic myocarditis and suggest the possibility of experimental therapy with L-carnitine.

Full text

PDF
2071

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baseman J. B., Pappenheimer A. M., Jr, Gill D. M., Harper A. A. Action of diphtheria toxin in the guinea pig. J Exp Med. 1970 Dec 1;132(6):1138–1152. doi: 10.1084/jem.132.6.1138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bonventre P. F., Imhoff J. G. Studies on the mode of action of diphtheria toxin. I. Protein synthesis in guinea pig tissues. J Exp Med. 1966 Dec 1;124(6):1107–1122. doi: 10.1084/jem.124.6.1107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bressler R., Wittels B. The effect of diphtheria toxin on carnitine metabolism in the heart. Biochim Biophys Acta. 1965 Jun 15;104(1):39–45. doi: 10.1016/0304-4165(65)90217-5. [DOI] [PubMed] [Google Scholar]
  4. Challoner D. R., Mandelbaum I., Elliott W. Protective effect of L-carnitine in experimental intoxication with diphtheria toxin. J Lab Clin Med. 1971 Apr;77(4):616–628. [PubMed] [Google Scholar]
  5. Garland P. B., Randle P. J. Regulation of glucose uptake by muscles. 10. Effects of alloxan-diabetes, starvation, hypophysectomy and adrenalectomy, and of fatty acids, ketone bodies and pyruvate, on the glycerol output and concentrations of free fatty acids, long-chain fatty acyl-coenzyme A, glycerol phosphate and citrate-cycle intermediates in rat heart and diaphragm muscles. Biochem J. 1964 Dec;93(3):678–687. doi: 10.1042/bj0930678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gravina E., Gravina-Sanvitale G. Effect of carnitine on blood acetoacetate in fasting children. Clin Chim Acta. 1969 Feb;23(2):376–377. doi: 10.1016/0009-8981(69)90057-6. [DOI] [PubMed] [Google Scholar]
  7. Hagenfeldt L. A gas chromatographic method for the determination of individual free fatty acids in plasma. Clin Chim Acta. 1966 Feb;13(2):266–268. doi: 10.1016/0009-8981(66)90304-4. [DOI] [PubMed] [Google Scholar]
  8. Kreisberg R. A. Effect of diabetes and starvation on myocardial triglyceride and free fatty acid utilization. Am J Physiol. 1966 Feb;210(2):379–384. doi: 10.1152/ajplegacy.1966.210.2.379. [DOI] [PubMed] [Google Scholar]
  9. MARQUIS N. R., FRITZ I. B. ENZYMOLOGICAL DETERMINATION OF FREE CARNITINE CONCENTRATIONS IN RAT TISSUES. J Lipid Res. 1964 Apr;5:184–187. [PubMed] [Google Scholar]
  10. MILLER W. L., KRAKE J. J. Studies on lipid metabolism in mice treated with beta-hydroxy, gamma-betaine-butyric acid. Proc Soc Exp Biol Med. 1962 Jan;109:215–218. doi: 10.3181/00379727-109-27157. [DOI] [PubMed] [Google Scholar]
  11. MORGAN H. E., HENDERSON M. J., REGEN D. M., PARK C. R. Regulation of glucose uptake in muscle. I. The effects of insulin and anoxia on glucose transport and phosphorylation in the isolated, perfused heart of normal rats. J Biol Chem. 1961 Feb;236:253–261. [PubMed] [Google Scholar]
  12. MORRISON W. R., SMITH L. M. PREPARATION OF FATTY ACID METHYL ESTERS AND DIMETHYLACETALS FROM LIPIDS WITH BORON FLUORIDE--METHANOL. J Lipid Res. 1964 Oct;5:600–608. [PubMed] [Google Scholar]
  13. PEARSON D. J., TUBBS P. K. TISSUE LEVELS OF ACID-INSOLUBLE CARNITINE IN RAT HEART. Biochim Biophys Acta. 1964 Dec 2;84:772–773. doi: 10.1016/0926-6542(64)90042-3. [DOI] [PubMed] [Google Scholar]
  14. Söling H. D., Appels A. Effects of L-carnitine on utilization of ketone bodies and glucose in eviscerated, nephrectomized rats. Biochim Biophys Acta. 1968 Apr 16;158(1):162–164. doi: 10.1016/0304-4165(68)90087-1. [DOI] [PubMed] [Google Scholar]
  15. WITTELS B., BRESSLER R. BIOCHEMICAL LESION OF DIPHTHERIA TOXIN IN THE HEART. J Clin Invest. 1964 Apr;43:630–637. doi: 10.1172/JCI104948. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES