Skip to main content
Log in

Advantageous effect of low-molecular-weight heparin administration on hepatic mitochondrial redox state

  • Original Articles
  • Published:
Research in Experimental Medicine

Abstract

The effect of low-molecular-weight heparin (LMWH) on hepatic mitochondrial metabolism was compared with that of unfractionated heparin (UH) after the intravenous administration of these two kinds of heparin to normal rabbits. The magnitude of decrease in blood triglyceride levels 5 min after administration of UH (200 U/kg) was significantly greater than after LMWH (200 U/kg). Free fatty acid levels in the blood were significantly higher after this dose of UH than after LMWH. Blood total ketone body levels (acetoacetate+3-hydroxybutyrate) 15 min after injection of 50 U/kg of UH were significantly higher than those after a dose of 50 U/kg of LMWH, and levels after 200 U/kg of UH were significantly higher than those after 200 U/kg of LMWH at 15, 30, 45 and 60 min. Enhanced ketogenesis was not noted after LMWH at any of the doses, or after UH at 3 U/kg. Arterial ketone body ratio (AKBR; acetoacetate/3-hydroxybutyrate), which reflects the hepatic mitochondrial oxidation-reduction state (NAD+/NADH), was maintained above 1.0 in all groups except in the U-200 group, while AKBR in that group was significantly decreased to 0.99±0.14 at 30 min, and further decreased to 0.80±0.08 at 60 min. These results indicate that LMWH has less effect on lipolysis than UH and does not enhance ketogenesis, resulting in less deterioration of mitochondrial redox state.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Wilson NV, Melissari E, Standfield NJ, Kakkar VV (1991) Intra-operative antithrombotic therapy with low molecular weight heparin in aortic surgery. How should heparin be administered? Eur J Vasc Surg 5:565–569

    Article  PubMed  CAS  Google Scholar 

  2. Deuber HJ, Schulz W (1991) Reduced lipid concentrations during four years of dialysis with low molecular weight heparin. Kidney Int 40:496–500

    PubMed  CAS  Google Scholar 

  3. Persson E, Nordenström J, Nilsson-Ehle P, Hagenfeldt L (1985) Lipolytic and anticoagulant activities of a low molecular weight fragment of heparin. Eur J Clin Invest 15: 215–220

    PubMed  CAS  Google Scholar 

  4. Bergqvist D, Hedner U, Sjörin E, Holmer E (1983) Anticoagulant effects of two types of low molecular weight heparin administered subcutaneously. Thromb Res 32:381–391

    Article  PubMed  CAS  Google Scholar 

  5. Bengtsson G, Olivecrona T, Höök M, Riesenfeld J, Lindahl U (1980) Interaction of lipoprotein lipase with native and modified heparin-like polysaccharides. Biochem J 189:625–633

    PubMed  CAS  Google Scholar 

  6. Connor WE, Hoak JC, Warner ED (1963) Massive thrombosis produced by fatty acid infusion. J Clin Invest 42:860–866

    PubMed  CAS  Google Scholar 

  7. Mahadevan V, Singh H, Lundberg W (1965) Effects of saturated and unsaturated fatty acids on blood platelet aggregation in vitro. (30702) Proc Soc Exp Biol Med 121:82–85

    Google Scholar 

  8. Salzman EW, Rosenberg RD, Smith MH, Lindon JN, Favreau L (1980) Effect of heparin and heparin fractions on platelet aggregation. J Clin Invest 65:64–73

    Article  PubMed  CAS  Google Scholar 

  9. Tansey MJB, Opie LH (1983) Relation between plasma free fatty acids and arrhythmias within the first twelve hours of acute myocardial infarction. Lancet II:419–422

    Article  Google Scholar 

  10. Van Harken DR, Dixon CW, Heimberg M (1969) Hepatic lipid metabolism in experimental diabetes. V. The effect of concentration of oleate on metabolism of triglycerides and on ketogenesis. J Biol Chem 244:2278–2285

    PubMed  Google Scholar 

  11. Siess EA, Kientsch-Engel RI, Wieland OH (1982) Role of free oxaloacetate in ketogenesis. Derivation from the direct measurement of mitochondrial [3-hydroxybutyrate]/[acetoacetate] ratio in hepatocytes. Eur J Biochem 121:493–499

    Article  PubMed  CAS  Google Scholar 

  12. Lehninger AL, Sudduth HC, Wise JB (1960) D-β-Hydroxybutyric dehydrogenase of mitochondria. J Biol Chem 235:2450–2455

    PubMed  CAS  Google Scholar 

  13. Ozawa K, Aoyama H, Yasuda K, Shimahara Y, Nakatani T, Tanaka J, Yamamoto M, Kamiyama Y, Tobe T (1983) Metabolic abnormalities associated with postoperative organ failure—a redox theory. Arch Surg 118:1245–1251

    PubMed  CAS  Google Scholar 

  14. Mellanby J, Williamson DH (1974) Acetoacetate. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic Press, New York, pp, 1840–1843

    Google Scholar 

  15. Williamson DH, Mellanby J (1974) D-(−)−3-Hydroxybutyrate. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic Press, New York, pp, 1836–1839

    Google Scholar 

  16. Heimberg M, Weinstein J, Kohout M (1969) The effects of glucagon, dibutyryl cyclic adenosine 3′, 5′-monophosphate, and concentration of free fatty acid on hepatic lipid metabolism. J Biol Chem 244:5131–5139

    PubMed  CAS  Google Scholar 

  17. MacGarry JD, Foster DW (1980) Regulation of hepatic fatty acid oxidation and ketone body production. Annu Rev Biochem 49:395–420

    Article  Google Scholar 

  18. Keller U, Gerber PPG, Stauffacher W (1988) Fatty acid-independent inhibition of hepatic ketone body production by insulin in humans. Am J Physiol 254:E694-E699

    PubMed  CAS  Google Scholar 

  19. Nakatani T, Ozawa K, Asano M, Ukikusa M, Kamiyama Y, Tobe T (1981) Changes in predominant energy substrate after hepatectomy. Life Sci 28:257–264

    Article  PubMed  CAS  Google Scholar 

  20. Nakatani T, Yasuda K, Ozawa K (1988) Hyperglycemic hyperosmolar nonketotic dehydration in relation to blood ketone body ratio, in partially hepatectomized rabbits. Am J Surg 155:559–563

    Article  PubMed  CAS  Google Scholar 

  21. Nishikawa K, Nishihira T, Taki Y, Morimoto T, Yokoo N, Shimahara Y, Mori K, Yamaoka Y, Ozawa K (1988) Biological significance of enhanced ketogenesis in hepatectomized patients and aged rat liver mitochondria. Surg Res Commun 3:251–261

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sasaki, H., Yamaguchi, T., Kumada, K. et al. Advantageous effect of low-molecular-weight heparin administration on hepatic mitochondrial redox state. Res. Exp. Med. 194, 139–145 (1994). https://doi.org/10.1007/BF02576374

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02576374

Key words

Navigation