Skip to main content
Log in

The importance of myocardial amino acids during ischemia and reperfusion in dilated left ventricle of patients with degenerative mitral valve disease

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Taurine, glutamine, glutamate, aspartate, and alanine are the most abundant intracellular free amino acids in human heart. The myocardial concentration of these amino acids changes during ischemia and reperfusion due to alterations in metabolic and ionic homeostasis. We hypothesized that dilated left ventricle secondary to mitral valve disease has different levels of amino acids compared to the right ventricle and that such differences determine the extent of amino acids' changes during ischemia and reperfusion. Myocardial concentration of amino acids was measured in biopsies collected from left and right ventricles before cardioplegic arrest (Custodiol HTK) and 10 min after reperfusion in patients undergoing mitral valve surgery. The dilated left ventricle had markedly higher (P < 0.05) concentrations (nmol/mg wet weight) of taurine (17.0 ± 1.5 vs. 10.9 ± 1.5), glutamine (20.5 ± 2.4 vs. 12.1 ± 1.2), and glutamate (18.3 ± 2.2 vs. 11.4 ± 1.5) when compared to right ventricle. There were no differences in the basal levels of alanine or aspartate. Upon reperfusion, a significant (P < 0.05) fall in taurine and glutamine was seen only in the left ventricle. These changes are likely to be due to transport (taurine) and/or metabolism (glutamine). There was a marked increase in the alanine to glutamate ratio in both ventricles indicative of ischemic stress which was confirmed by global release of lactate during reperfusion. This study shows that in contrast to the right ventricle, the dilated left ventricle had remodeled to accumulate amino acids which are used during ischemia and reperfusion. Whether these changes reflect differences in degree of cardioplegic protection between the two ventricles remain to be investigated.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Caputo M, Bryan AJ, Calafiore AM et al (1998) Intermittent antegrade hyperkalaemic warm blood cardioplegia supplemented with magnesium prevents myocardial substrate derangement in patients undergoing coronary artery bypass surgery. Eur J Cardiothorac Surg 14:596–601. doi:10.1016/S1010-7940(98)00247-4

    Article  CAS  PubMed  Google Scholar 

  2. Caputo M, Dihmis WC, Bryan AJ et al (1998) Warm blood hyperkalaemic reperfusion (‘hot shot’) prevents myocardial substrate derangement in patients undergoing coronary artery bypass surgery. Eur J Cardiothorac Surg 13:559–564. doi:10.1016/S1010-7940(98)00056-6

    Article  CAS  PubMed  Google Scholar 

  3. Suleiman MS, Halestrap AP, Griffiths EJ (2001) Mitochondria: a target for myocardial protection. Pharmacol Ther 89:29–46. doi:10.1016/S0163-7258(00)00102-9

    Article  CAS  PubMed  Google Scholar 

  4. Suleiman MS, Zacharowski K, Angelini GD (2008) Inflammatory response and cardioprotection during open-heart surgery: the importance of anaesthetics. Br J Pharmacol 153:21–33. doi:10.1038/sj.bjp.0707526

    Article  CAS  PubMed  Google Scholar 

  5. Tritto FP, Inserte J, Garcia-Dorado D et al (1998) Sodium/hydrogen exchanger inhibition reduces myocardial reperfusion edema after normothermic cardioplegia. J Thorac Cardiovasc Surg 115:709–715. doi:10.1016/S0022-5223(98)70337-X

    Article  CAS  PubMed  Google Scholar 

  6. Garcia-Dorado D, Oliveras J (1993) Myocardial oedema: a preventable cause of reperfusion injury? Cardiovasc Res 27:1555–1563. doi:10.1093/cvr/27.9.1555

    Article  CAS  PubMed  Google Scholar 

  7. Ruiz-Meana M, Garcia-Dorado D, Gonzalez MA et al (1995) Effect of osmotic stress on sarcolemmal integrity of isolated cardiomyocytes following transient metabolic inhibition. Cardiovasc Res 30:64–69

    CAS  PubMed  Google Scholar 

  8. Schaffer SW, Solodushko V, Kakhniashvili D (2002) Beneficial effect of taurine depletion on osmotic sodium and calcium loading during chemical hypoxia. Am J Physiol Cell Physiol 282:C1113–C1120

    CAS  PubMed  Google Scholar 

  9. Suleiman MS, Chapman RA (1993) Calcium paradox in newborn and adult guinea-pig hearts: changes in intracellular taurine and the effects of extracellular magnesium. Exp Physiol 78:503–516

    CAS  PubMed  Google Scholar 

  10. Suleiman MS, Chapman RA (1993) Changes in the principal free intracellular amino acids in the Langendorff perfused guinea pig heart during arrest with calcium-free or high potassium media. Cardiovasc Res 27:1810–1814. doi:10.1093/cvr/27.10.1810

    Article  CAS  PubMed  Google Scholar 

  11. Suleiman MS, Fernando HC, Dihmis WC et al (1993) A loss of taurine and other amino acids from ventricles of patients undergoing bypass surgery. Br Heart J 69:241–245. doi:10.1136/hrt.69.3.241

    Article  CAS  PubMed  Google Scholar 

  12. Huxtable RJ (1993) Taurine and the heart. Cardiovasc Res 27:1136–1137. doi:10.1093/cvr/27.6.1136a

    Article  CAS  PubMed  Google Scholar 

  13. Suleiman MS, Rodrigo GC, Chapman RA (1992) Interdependence of intracellular taurine and sodium in guinea pig heart. Cardiovasc Res 26:897–905. doi:10.1093/cvr/26.9.897

    Article  CAS  PubMed  Google Scholar 

  14. Suleiman MS, Moffatt AC, Dihmis WC et al (1997) Effect of ischaemia and reperfusion on the intracellular concentration of taurine and glutamine in the hearts of patients undergoing coronary artery surgery. Biochim Biophys Acta 1324:223–231. doi:10.1016/S0005-2736(96)00225-8

    Article  CAS  PubMed  Google Scholar 

  15. Ascione R, Gomes WJ, Angelini GD et al (1998) Warm blood cardioplegia reduces the fall in the intracellular concentration of taurine in the ischaemic/reperfused heart of patients undergoing aortic valve surgery. Amino Acids 15:339–350. doi:10.1007/BF01320898

    Article  CAS  PubMed  Google Scholar 

  16. Lotto AA, Ascione R, Caputo M et al (2003) Myocardial protection with intermittent cold blood during aortic valve operation: antegrade versus retrograde delivery. Ann Thorac Surg 76:1227–1233. doi:10.1016/S0003-4975(03)00840-3

    Article  PubMed  Google Scholar 

  17. Cooper MW, Lombardini JB (1981) Elevated blood taurine levels after myocardial infarction of cardiovascular surgery: is there any significance? Adv Exp Med Biol 139:191–205

    CAS  PubMed  Google Scholar 

  18. Lombardini JB, Bricker DL (1981) Effects of cardiovascular surgery on blood concentrations of taurine and amino acids. Proc Soc Exp Biol Med 167:498–505

    CAS  PubMed  Google Scholar 

  19. Lombardini JB, Cooper MW (1981) Elevated blood taurine levels in acute and evolving myocardial infarction. J Lab Clin Med 98:849–859

    CAS  PubMed  Google Scholar 

  20. Rennie MJ, Bowtell JL, Bruce M et al (2001) Interaction between glutamine availability and metabolism of glycogen, tricarboxylic acid cycle intermediates and glutathione. J Nutr 131:2488S–2490S discussion 2496S–7S

    CAS  PubMed  Google Scholar 

  21. Taegtmeyer H (1994) Energy metabolism of the heart: from basic concepts to clinical applications. Curr Probl Cardiol 19:59–113. doi:10.1016/0146-2806(94)90008-6

    Article  CAS  PubMed  Google Scholar 

  22. Conway MA, Bottomley PA, Ouwerkerk R (1998) Mitral regurgitation: impaired systolic function, eccentric hypertrophy, and increased severity are linked to lower phosphocreatine/ATP ratios in humans. Circulation 97:1716–1723

    CAS  PubMed  Google Scholar 

  23. Lin H, Suleiman MS (2003) Cariporide enhances lactate clearance upon reperfusion but does not alter lactate accumulation during global ischaemia. Pflugers Arch 447:8–13. doi:10.1007/s00424-003-1134-8

    Article  CAS  PubMed  Google Scholar 

  24. Roncalli J, Smih F, Desmoulin F et al (2007) NMR and cDNA array analysis prior to heart failure reveals an increase of unsaturated lipids, a glutamine/glutamate ratio decrease and a specific transcriptome adaptation in obese rat heart. J Mol Cell Cardiol 42:526–539. doi:10.1016/j.yjmcc.2006.11.007

    Article  CAS  PubMed  Google Scholar 

  25. Suleiman MS, Dihmis WC, Caputo M et al (1997) Changes in myocardial concentration of glutamate and aspartate during coronary artery surgery. Am J Physiol 272:H1063–H1069

    CAS  PubMed  Google Scholar 

  26. Carabello BA (2008) The current therapy for mitral regurgitation. J Am Coll Cardiol 52:319–326. doi:10.1016/j.jacc.2008.02.084

    Article  PubMed  Google Scholar 

  27. Peterson MB, Mead RJ, Welty JD (1973) Free amino acids in congestive heart failure. J Mol Cell Cardiol 5:139–147. doi:10.1016/0022-2828(73)90047-3

    Article  CAS  PubMed  Google Scholar 

  28. Yagihashi T, Wakabayashi Y, Kezuka J et al (2007) Changes in vitreous amino acid concentrations in a rabbit model of cataract surgery. Acta Ophthalmol Scand 85:303–308. doi:10.1111/j.1600-0420.2006.00829.x

    Article  CAS  PubMed  Google Scholar 

  29. Huxtable RJ (1992) Physiological actions of taurine. Physiol Rev 72:101–163

    CAS  PubMed  Google Scholar 

  30. Chapman RA, Suleiman MS, Earm YE (1993) Taurine and the heart. Cardiovasc Res 27:358–363. doi:10.1093/cvr/27.3.358

    Article  CAS  PubMed  Google Scholar 

  31. Takahashi K, Ohyabu Y, Takahashi K et al (2003) Taurine renders the cell resistant to ischemia-induced injury in cultured neonatal rat cardiomyocytes. J Cardiovasc Pharmacol 41:726–733. doi:10.1097/00005344-200305000-00009

    Article  CAS  PubMed  Google Scholar 

  32. Takatani T, Takahashi K, Uozumi Y et al (2004) Taurine inhibits apoptosis by preventing formation of the Apaf-1/caspase-9 apoptosome. Am J Physiol Cell Physiol 287:C949–C953. doi:10.1152/ajpcell.00042.2004

    Article  CAS  PubMed  Google Scholar 

  33. Takatani T, Takahashi K, Uozumi Y et al (2004) Taurine prevents the ischemia-induced apoptosis in cultured neonatal rat cardiomyocytes through Akt/caspase-9 pathway. Biochem Biophys Res Commun 316:484–489. doi:10.1016/j.bbrc.2004.02.066

    Article  CAS  PubMed  Google Scholar 

  34. Bkaily G, Jaalouk D, Sader S et al (1998) Taurine indirectly increases [Ca]i by inducing Ca2+ influx through the Na(+)-Ca2+ exchanger. Mol Cell Biochem 188:187–197. doi:10.1023/A:1006806925739

    Article  CAS  PubMed  Google Scholar 

  35. Schaffer SW, Nguyen K, Ballard C et al (1996) Regulation of Ca2+ transport by insulin and taurine. Interaction at the level of the Na(+)-Ca2+ exchanger. Adv Exp Med Biol 403:551–560

    CAS  PubMed  Google Scholar 

  36. Bkaily G, Haddad G, Jaalouk D et al (1996) Modulation of Ca2+ and Na+ transport by taurine in heart and vascular smooth muscle. Adv Exp Med Biol 403:263–273

    CAS  PubMed  Google Scholar 

  37. Rennie MJ, Tadros L, Khogali S et al (1994) Glutamine transport and its metabolic effects. J Nutr 124:1503S–1508S

    CAS  PubMed  Google Scholar 

  38. King N, McGivan JD, Griffiths EJ et al (2003) Glutamate loading protects freshly isolated and perfused adult cardiomyocytes against intracellular ROS generation. J Mol Cell Cardiol 35:975–984. doi:10.1016/S0022-2828(03)00182-2

    Article  CAS  PubMed  Google Scholar 

  39. Williams H, King N, Griffiths EJ et al (2001) Glutamate-loading stimulates metabolic flux and improves cell recovery following chemical hypoxia in isolated cardiomyocytes. J Mol Cell Cardiol 33:2109–2119. doi:10.1006/jmcc.2000.1474

    Article  CAS  PubMed  Google Scholar 

  40. Robertson JM, Vinten-Johansen J, Buckberg GD et al (1984) Safety of prolonged aortic clamping with blood cardioplegia. I. Glutamate enrichment in normal hearts. J Thorac Cardiovasc Surg 88:395–401

    CAS  PubMed  Google Scholar 

  41. Rosenkranz ER, Okamoto F, Buckberg GD et al (1986) Safety of prolonged aortic clamping with blood cardioplegia. III. Aspartate enrichment of glutamate-blood cardioplegia in energy-depleted hearts after ischemic and reperfusion injury. J Thorac Cardiovasc Surg 91:428–435

    CAS  PubMed  Google Scholar 

  42. Rosenkranz ER, Okamoto F, Buckberg GD et al (1984) Safety of prolonged aortic clamping with blood cardioplegia. II. Glutamate enrichment in energy-depleted hearts. J Thorac Cardiovasc Surg 88:402–410

    CAS  PubMed  Google Scholar 

  43. Suleiman MS, Chapman RA (1990) Effect of temperature on the rise in intracellular sodium caused by calcium depletion in ferret ventricular muscle and the mechanism of the alleviation of the calcium paradox by hypothermia. Circ Res 67:1238–1246

    CAS  PubMed  Google Scholar 

  44. Carter JM, Bell NJ, Suleiman MS (1996) The use of Langendorff perfused guinea-pig heart to study the efflux of amino acids from heart cells. Biochem Soc Trans 24:482S

    CAS  PubMed  Google Scholar 

  45. Pisarenko OI (1996) Mechanisms of myocardial protection by amino acids: facts and hypotheses. Clin Exp Pharmacol Physiol 23:627–633. doi:10.1111/j.1440-1681.1996.tb01748.x

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to acknowledge the help and support of the staff in the cardiac surgery unit at Ospedale Civile “Umberto I,” Venezia-Mestre, Italy. This study was supported by the British Heart Foundation and the Garfield Weston Trust.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M.-S. Suleiman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Venturini, A., Ascione, R., Lin, H. et al. The importance of myocardial amino acids during ischemia and reperfusion in dilated left ventricle of patients with degenerative mitral valve disease. Mol Cell Biochem 330, 63–70 (2009). https://doi.org/10.1007/s11010-009-0101-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-009-0101-x

Keywords

Navigation