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. 1980 Mar 15;186(3):701–711. doi: 10.1042/bj1860701

Utilization of energy-providing substrates in the isolated working rat heart.

H Taegtmeyer, R Hems, H A Krebs
PMCID: PMC1161705  PMID: 6994712

Abstract

1. An improved perfusion system for the isolated rat heart is described. It is based on the isolated working heart of Neely, Liebermeister, Battersby & Morgan (1967) (Am. J. Physiol. 212, 804-814) and allows the measurement of metabolic rates and cardiac performance at a near-physiological workload. The main improvements concern better oxygenation of the perfusion medium and greater versatility of the apparatus. Near-physiological performance (cardiac output and aortic pressure) was maintained for nearly 2 h as compared with 30 min or less in the preparations of earlier work. 2. The rates of energy release (O2 uptake and substrate utilization) were 40-100% higher than those obtained by previous investigators, who used hearts at subphysiological workloads. 3. Values are given for the rates of utilization of glucose, lactate, oleate, acetate and ketone bodies, for O2 consumption and for the relative contributions of various fuels to the energy supply of the heart. Glucose can be replaced to a large extent by lactate, oleate or acetate, but not by ketone bodies. 4. Apart from quantitative differences there were also major qualitative differences between the present and previous preparations. Thus insulin was not required for maximal rates of glucose consumption at near-physiological, in contrast with subphysiological, workloads when glucose was the sole added substrate. When glucose oxidation was suppressed by the addition of other oxidizable substrates (lactate, acetate or acetoacetate), insulin increased the contribution of glucose as fuel for cardiac energy production at high workload. 5. In view of the major effects of workload on cardiac metabolism, experimentation on hearts performing subphysiologically or unphysiologically is of limited value to the situation in vivo.

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Selected References

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

  1. BLEEHEN N. M., FISHER R. B. The action of insulin in the isolated rat heart. J Physiol. 1954 Feb 26;123(2):260–276. doi: 10.1113/jphysiol.1954.sp005049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Elzinga G., Westerhof N. How to quantify pump function of the heart. The value of variables derived from measurements on isolated muscle. Circ Res. 1979 Mar;44(3):303–308. doi: 10.1161/01.res.44.3.303. [DOI] [PubMed] [Google Scholar]
  3. Fanburg B. L., Posner B. I. Labeling of RNA in the perfused heart: the problem of bacterial contamination. Biochim Biophys Acta. 1969 Jun 17;182(2):577–579. doi: 10.1016/0005-2787(69)90214-7. [DOI] [PubMed] [Google Scholar]
  4. GARLAND P. B., RANDLE P. J., NEWSHOLME E. A. CITRATE AS AN INTERMEDIARY IN THE INHIBITION OF PHOSPHOFRUCTOKINASE IN RAT HEART MUSCLE BY FATTY ACIDS, KETONE BODIES, PYRUVATE, DIABETES, AND STARVATION. Nature. 1963 Oct 12;200:169–170. doi: 10.1038/200169a0. [DOI] [PubMed] [Google Scholar]
  5. Gamble W. J., Conn P. A., Kumar A. E., Plenge R., Monroe R. G. Myocardial oxygen consumption of blood-perfused, isolated, supported, rat heart. Am J Physiol. 1970 Sep;219(3):604–612. doi: 10.1152/ajplegacy.1970.219.3.604. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Hems R., Ross B. D., Berry M. N., Krebs H. A. Gluconeogenesis in the perfused rat liver. Biochem J. 1966 Nov;101(2):284–292. doi: 10.1042/bj1010284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hess D. S., Bache R. J. Transmural distribution of myocardial blood flow during systole in the awake dog. Circ Res. 1976 Jan;38(1):5–15. doi: 10.1161/01.res.38.1.5. [DOI] [PubMed] [Google Scholar]
  9. Holloszy J. O., Narahara H. T. Studies of tissue permeability. X. Changes in permeability to 3-methylglucose associated with contraction of isolated frog muscle. J Biol Chem. 1965 Sep;240(9):3493–3500. [PubMed] [Google Scholar]
  10. Kobayashi K., Neely J. R. Control of maximum rates of glycolysis in rat cardiac muscle. Circ Res. 1979 Feb;44(2):166–175. doi: 10.1161/01.res.44.2.166. [DOI] [PubMed] [Google Scholar]
  11. Krebs H. A., Eggleston L. V. Metabolism of acetoacetate in animal tissues. 1. Biochem J. 1945;39(5):408–419. [PMC free article] [PubMed] [Google Scholar]
  12. Morgan H. E., Neely J. R., Wood R. E., Liébecq C., Liebermeister H., Park C. R. Factors affecting glucose transport in heart muscle and erythrocytes. Fed Proc. 1965 Sep-Oct;24(5):1040–1045. [PubMed] [Google Scholar]
  13. Neely J. R., Denton R. M., England P. J., Randle P. J. The effects of increased heart work on the tricarboxylate cycle and its interactions with glycolysis in the perfused rat heart. Biochem J. 1972 Jun;128(1):147–159. doi: 10.1042/bj1280147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Neely J. R., Liebermeister H., Battersby E. J., Morgan H. E. Effect of pressure development on oxygen consumption by isolated rat heart. Am J Physiol. 1967 Apr;212(4):804–814. doi: 10.1152/ajplegacy.1967.212.4.804. [DOI] [PubMed] [Google Scholar]
  15. Neely J. R., Liebermeister H., Morgan H. E. Effect of pressure development on membrane transport of glucose in isolated rat heart. Am J Physiol. 1967 Apr;212(4):815–822. doi: 10.1152/ajplegacy.1967.212.4.815. [DOI] [PubMed] [Google Scholar]
  16. Opie L. H. Effect of fatty acids on contractility and rhythm of the heart. Nature. 1970 Sep 5;227(5262):1055–1056. doi: 10.1038/2271055a0. [DOI] [PubMed] [Google Scholar]
  17. Opie L. H., Mansford K. R., Owen P. Effects of increased heart work on glycolysis and adenine nucleotides in the perfused heart of normal and diabetic rats. Biochem J. 1971 Sep;124(3):475–490. doi: 10.1042/bj1240475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Oram J. F., Bennetch S. L., Neely J. R. Regulation of fatty acid utilization in isolated perfused rat hearts. J Biol Chem. 1973 Aug 10;248(15):5299–5309. [PubMed] [Google Scholar]
  19. Randle P. J., England P. J., Denton R. M. Control of the tricarboxylate cycle and its interactions with glycolysis during acetate utilization in rat heart. Biochem J. 1970 May;117(4):677–695. doi: 10.1042/bj1170677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. SHIPP J. C. INTERRELATION BETWEEN CARBOHYDRATE AND FATTY ACID METABOLISM OF ISOLATED PERFUSED RAT HEART. Metabolism. 1964 Sep;13:852–867. doi: 10.1016/0026-0495(64)90054-x. [DOI] [PubMed] [Google Scholar]
  21. WILLIAMSON J. R. Effects of insulin and diet on the metabolism of L-lactate and glucose by the perfused rat heart. Biochem J. 1962 May;83:377–383. doi: 10.1042/bj0830377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. WILLIAMSON J. R. GLYCOLYTIC CONTROL MECHANISMS. I. INHIBITION OF GLYCOLYSIS BY ACETATE AND PYRUVATE IN THE ISOLATED, PERFUSED RAT HEART. J Biol Chem. 1965 Jun;240:2308–2321. [PubMed] [Google Scholar]
  23. WILLIAMSON J. R., KREBS H. A. Acetoacetate as fuel of respiration in the perfused rat heart. Biochem J. 1961 Sep;80:540–547. doi: 10.1042/bj0800540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Whitelaw E., Williamson D. H. Effects of lactation of ketogenesis from oleate or butyrate in rat hepatocytes. Biochem J. 1977 Jun 15;164(3):521–528. doi: 10.1042/bj1640521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Williamson D. H., Bates M. W., Page M. A., Krebs H. A. Activities of enzymes involved in acetoacetate utilization in adult mammalian tissues. Biochem J. 1971 Jan;121(1):41–47. doi: 10.1042/bj1210041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Williamson J. R. Effects of insulin and starvation on the metabolism of acetate and pyruvate by the perfused rat heart. Biochem J. 1964 Oct;93(1):97–106. doi: 10.1042/bj0930097. [DOI] [PMC free article] [PubMed] [Google Scholar]

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