Myocardial release of hypoxanthine and lactate during coronary angioplasty

A quickly reversibe phenomenon, but for how long?
  • Patrick W. Serruys
  • Federico Piscione
  • William Wijns
  • Johan A. J. Hegge
  • Eef Harmsen
  • Marcel Van Den Brand
  • Pim De Feyter
  • Paul G. Hugenholtz
  • Jan W. De Jong
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 101)


Until recently the assessment of alteration in myocardial metabolism in man early after an abrupt occlusion of a major coronary artery has not been feasible. Percutaneous transluminal coronary angioplasty (PTCA), however, now provides a unique opportunity to study the time course of these metabolic changes during the transient interruption of coronary flow by the balloon occlusion sequence in patients with single-vessel disease and without angiographically demonstrable collateral circulation [1, 2]. The need to detect any persisting metabolic or mechanical dysfunction becomes of even greater concern as the number of dilated vessels and the duration of balloon inflation tend to increase, thereby enhancing both the extent and the severity of ischemia. The risk exists that the damage induced by the intervention may exceed its benefit.


Coronary Sinus Coronary Occlusion Reactive Hyperemia Occlusion Pressure Coronary Vascular Resistance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Serruys PW, Wijns W, van den Brand M et al (1984) Left ventricular performance, regional blood flow, wall motion and lactate metabolism during transluminal angioplasty. Circulation 70: 25–36PubMedCrossRefGoogle Scholar
  2. 2.
    Serruys PW, van den Brand M, Brower RW, Hugenholtz PG (1984) Left ventricular hemodynamics, regional blood flow and lactate metabolism during balloon occlusion: Can we alter the sequence of ischemic events? In: Rutishauser W, Roskam MW (eds) Silent myocardial ischemia. Berlin-Heidelberg-New York-Tokyo: Springer Verlag, 37–44Google Scholar
  3. 3.
    de Jong JW (1979) Biochemistry of acutely ischemic myocardium. Schaper W (ed) The pathophysiology of myocardial perfusion. Amsterdam: Elsevier/North-Holland Biomedical Press, 719–750Google Scholar
  4. 4.
    Remme WJ, de Jong JW, Verdouw PD (1979) Effect of pacing-induced myocardial ischemia on hypoxanthine efflux from the human heart. Am J Cardiol 40: 55–62Google Scholar
  5. 5.
    Hartwick RA, Krstulovic AM, Brown PR (1979) Identification and quantitation of nucleosides, bases and other UV-absorbing compounds in serum, using reversed-phase high-performance liquid chromatography. II Evaluation of human sera. J Chromatogr 186: 659–676PubMedCrossRefGoogle Scholar
  6. 6.
    Harmsen E, de Jong JW, Serruys PW (1981) Hypoxanthine production by ischemic heart demonstrated by high pressure liquid chromatography of blood purine nucleosides and oxypurines. Clin Chimica Acta 115: 73–84Google Scholar
  7. 7.
    Apstein CS, Puchner E, Brachfeld N (1979) Improved automated lactate determination. Anal Biochem 38: 20–34CrossRefGoogle Scholar
  8. 8.
    Chatterjee SK, Bhattacharya M, Barlow JJ (1979) A simple, specific radiometric assay for 5’-nucleotidase. Anal Biochem 95: 497–506PubMedCrossRefGoogle Scholar
  9. 9.
    de Jong JW, Keijzer E, Uitendaal MP, Harmsen E (1980) Further purification of adenosine kinase from rat heart using affinity and ion-exchange chromatography. Anal Biochem 101: 407–412PubMedCrossRefGoogle Scholar
  10. 10.
    Metha J, Pepine CJ (1978) Effect of sublingual nitroglycerin on regional flow in patients with and without coronary disease. Circulation 58: 803–807Google Scholar
  11. 11.
    Manning AS, Hearse DJ, Dennis SC, Bullock GR, Coltard DJ (1980) Myocardial ischemia: an isolated, globally perfused rat heart model for metabolic and pharmacological studies. Eur J Cardiol 11: 1–21PubMedGoogle Scholar
  12. 12.
    Wilson DF, Owens CS, Erecinska M (1979) Quantitative dependence of mitochondrial oxidative Aphosphorylation on oxygen concentration. A new mathematical model. Arch Biochem Biophys 195: 494–504PubMedCrossRefGoogle Scholar
  13. 13.
    Danforth WH, Naegle S, Bing RJ (1960) Effects of ischemia and reoxygenation on glycolytic reactions and adenosine triphosphate in heart muscle. Circ Res 8: 965–971PubMedGoogle Scholar
  14. 14.
    Garlick BP, Radda GK, Seeley PJ (1979) Studies of acidosis in the ischemic heart by phosphorus nuclear magnetic resonance. Biochem J 184: 547–554PubMedGoogle Scholar
  15. 15.
    Hearse DJ (1979) Oxygen deprivation and early myocardial contractile failure. Reassessment of the possible role of adenosine triphosphate. Am J Cardiol 44: 1115–1120PubMedCrossRefGoogle Scholar
  16. 16.
    Hearse DJ, Crome R, Yellon DM, Wyse R (1983) Metabolic and flow correlates of myocardial ischemia. Cardiovasc Res 17: 452–458PubMedCrossRefGoogle Scholar
  17. 17.
    Apstein CS, Deckelbaum L, Mueller M, Hagopian L, Hood WB (1977) Graded global ischemia and reperfusion. Circulation 55: 864–872PubMedGoogle Scholar
  18. 18.
    Neely JR, Liedke AJ, Whitmer TJ, Rovetto MJ (1975) Relationship between coronary flow and adenosine triphosphate production from glycolysis and oxidative metabolism. Recent Adv Studies Cardiac Structure Metab 8: 301–321Google Scholar
  19. 19.
    de Jong JW, Goldstein S (1974) Changes in coronary venous inosine concentration and myocardial wall thickening during regional ischemia in the pig. Circ Res 35: 111–116PubMedGoogle Scholar
  20. 20.
    Das SK, Serruys PW, van den Brand M, Domenicucci S, Vletter WB, Roelandt J (1983) Acute echocardiographic changes during percutaneous coronary angioplasty and their relationship to coronary blood flow. J Cardiovasc Ultrasonogr 2: 269–271Google Scholar
  21. 21.
    Jaski BE, Serruys PW (1985) Epicardial wall motion and left ventricular function during coronary graft angioplasty in humans. J Am Coll Cardiol 6: 695–700PubMedCrossRefGoogle Scholar
  22. 22.
    Serruys PW, Wijns W, Grimm J, Slager C, Hess OM (1984) Effects of repeated transluminal occlusions during angioplasty on global and regional left ventricular chamber stiffness (abstr). Circulation 70 (Suppl II): 348Google Scholar
  23. 23.
    Bing OHL, Brooks WW, Nesser JV (1973) Heart muscle viability following hypoxia: protective effect of acidosis. Science 180: 1297–1298PubMedCrossRefGoogle Scholar
  24. 24.
    Dhalla NS, Das PK, Sharma GP (1978) Subcellular basis of cardiac contracture failure. J Mol Cell Cardiol 10: 363–385PubMedCrossRefGoogle Scholar
  25. 25.
    Kannegieser GJ, Lubbe WF, Opie LH (1975) Experimental myocardial infarction with left ventricular failure in the isolated perfused rat heart. Effects of propranolol and pacing. J Mol Cell Cardiol 7: 135–151CrossRefGoogle Scholar
  26. 26.
    de Boer LWV, Ingwall JS, Kloner RA, Braunwald E (1980) Prolonged derangements of canine myocardial purine metabolism after brief coronary artery occlusion not associated with anatomic evidence of necrosis. Proc Natl Acc Sci USA 77: 5471–5475CrossRefGoogle Scholar
  27. 27.
    de Jong JW, Harmsen E, de Tombe PP, Keijzer E (1983) Release of purine nucleosides and oxypurines from the isolated perfused rat heart. Adv Myocardiol 4: 339–345PubMedGoogle Scholar
  28. 28.
    Schrader J, Haddy FJ, Gerlach E (1979) Release of adenosine, inosine and hypoxanthine from the isolated guinea pig heart during hypoxia, flow-autoregulation and reactive hyperemia. Pfugers Arch 369: 251–257CrossRefGoogle Scholar
  29. 29.
    Berne RM (1980) The role of adenosine in the regulation of coronary blood flow. Circ Res 47: 807–813PubMedGoogle Scholar
  30. 30.
    Fox AC, Reed GE, Mellman H, Silk BB (1979) Release of nucleosides from canine- and human hearts as an index of prior ischemia. Am J Cardiol 43: 52–57PubMedCrossRefGoogle Scholar
  31. 31.
    Kugler G (1978) The effects of nitroglycerin on myocardial release of inosine, hypoxanthine and lactate during pacing induced angina. Basic Res Cardiol 73: 523–533PubMedCrossRefGoogle Scholar
  32. 32.
    Kugler G (1979) Myocardial release of lactate, inosine and hypoxanthine during atrial pacing and exercise-induced angina. Circulation 59: 43–49PubMedGoogle Scholar
  33. 33.
    Kugler G (1979) Myocardial release of inosine, hypoxanthine and lactate during pacing-induced angina in humans with coronary artery disease. Eur J Cardiol 9: 227–240PubMedGoogle Scholar
  34. 34.
    Brower RW, de Jong JW, Haalebos M et al (1982) Evaluation of cardioplegia in coronary artery bypass graft surgery. In: Just H, Tschirkov A, Schlosser V (eds) Kalziumantagonisten zur Kardioplegie und Myocardprotection in der offenen Herzchirurgie. Stuttgart: Thieme, 69–80Google Scholar
  35. 35.
    Serruys PW, de Jong JW, Harmsen E, Verdouw PD, Hugenholtz PG (1983) Effect of intracoronary nifedipine in high-energy phosphate metabolism during repeated pacing-induced angina and during experimental ischemia. In: Kaltenbach M and Neufield HN (eds) New therapy of ischemic heart disease and hypertension. Amsterdam: Excerpta Medica, 340–353Google Scholar
  36. 36.
    Edlund A, Berglund B, van Dome D et al (1985) Coronary flow regulation in patients with ischemic heart disease: release of purines and prostacyclin and the effect of inhibitors of prostaglandin formation. Circulation 6: 1113–1120CrossRefGoogle Scholar
  37. 37.
    Schoenberg MH, Fredholm BB, Hohlbach G (1985) Changes in acid-base status, lactate concentration and purine metabolics during reconstructive aortic surgery. Acta Chir Scand 151: 227–233PubMedGoogle Scholar
  38. 38.
    Drake AJ, Haines JR, Noble MIM (1980) Preferential uptake of lactate by the normal myocardium in dogs. Cardiovasc Res 14: 65–77PubMedCrossRefGoogle Scholar
  39. 39.
    Verdouw PW, Stam H (1980) In: Moret PR et al (eds) Lactate. Physiologic, methodologic and pathologic approach. Springer Verlag, Berlin: 207–223Google Scholar
  40. 40.
    Webb SC, Rickards AF, Poole-Wilson PA (1983) Coronary sinus potassium concentration recorded during coronary angioplasty. Br Heart J 50: 146–148PubMedCrossRefGoogle Scholar
  41. 41.
    Rothman MT, Baim DS, Simpson JB, Harrison DC (1982) Coronary hemodynamics during percutaneous transluminal coronary angioplasty. Am J Cardiol 49: 1615–1621PubMedCrossRefGoogle Scholar
  42. 42.
    Swain JL, Sabina RL, Hines J J, Greenfield Jr JC, Holmes EW (1984) Repetitive episodes of brief ischemia (12min) do not produce a cumulative depletion of high energy phosphate compounds. Cardiovasc Res 18: 264–269PubMedCrossRefGoogle Scholar
  43. 43.
    Verdouw PD, Remme WJ, de Jong JW, Breeman WAP (1979) Myocardial substrate utilization and hemodynamics following repeated coronary flow reduction in pigs. Basic Res Cardiol 74: 477–493Google Scholar
  44. 44.
    Gubdjarnason S, Mathes P, Ravens KG (1970) Functional compartmentation of ATP and creatine phosphates in heart muscle. J Mol Cell Card 1: 325–39CrossRefGoogle Scholar
  45. 45.
    Schrader J, Gerlach E (1976) Compartmentation of cardiac adenine nucleotides and formation of adenosine. Pflügers Archiv 367: 129–35PubMedCrossRefGoogle Scholar
  46. 46.
    Swain JL, Sabina RL, McHale PA, Greenfield JC Jr, Holmes EW (1982) Prolonged myocardial nucleotide depletion after brief ischemia in the open-chest dog. Am J Physiol 242: H818–H826PubMedGoogle Scholar
  47. 47.
    Vial C, Font B, Goldschmidt D, Pearlman AS, Delaye J (1978) Regional myocardial energetics during brief periods of coronary occlusion and reperfusion: Comparison with S-T segment changes. Cardiovasc Res 12: 470–476PubMedCrossRefGoogle Scholar
  48. 48.
    Rentrop KP, Cohen M, Blanke H, Phillips RA (1985) Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol 5: 587–592PubMedCrossRefGoogle Scholar
  49. 49.
    Probst P, Zangl W, Pachinger O (1985) Relation of coronary arterial occlusion pressure during percutaneous transluminal coronary angioplasty to presence of collaterals. Am J Cardiol 55: 1264–1269PubMedCrossRefGoogle Scholar
  50. 50.
    Meier B, Luethy P (1984) Coronary wedge pressure as predictor of recruitable collateral arteries. Circulation 70 (Suppl II): 266Google Scholar
  51. 51.
    Hearse DJ (1977) Reperfusion of the ischemic myocardium (editorial). J Mol Cell Cardiol 9: 605 - 616PubMedCrossRefGoogle Scholar
  52. 52.
    Mittnacht S, Sherman C, Farber JL (1981) Reversal of ischemic mitochondrial dysfunction. J Biol Chem 256: 3199–3206PubMedGoogle Scholar
  53. 53.
    Puri PS (1975) Contractile and biochemical effects of coronary reperfusion after extended periods of coronary occlusion. Am J Cardiol 36: 244–251PubMedCrossRefGoogle Scholar
  54. 54.
    Apstein CS, Deckelbaum L, Hagopian L, Hood WB (1978) Acute cardiac ischemia and reperfusion: contractility, relaxation and glycolysis. Am J Physiol 235: H637–H648PubMedGoogle Scholar
  55. 55.
    Lewis MJ, Honsmand PR, Claes VA, Brutsaert DL, Henderson AH (1980) Myocardial stiffness during hypoxia and reoxygenation contracture. Cardiovasc Res 14: 339–344PubMedCrossRefGoogle Scholar
  56. 56.
    Baily IA, Seymour AML, Radda GK (1981) A31P-NMR study of the effect of reflow on the ischaemic heart. Biochim Biophys Acta 637: 1–7CrossRefGoogle Scholar
  57. 57.
    Flaherty JT, Weisfeld ML, Buckley BH, Gardner TJ, Gott VT, Jacobus WE (1982) Mechanism of ischemic myocardial cell damage assessed by phosphorus-31 nuclear magnetic resonance. Circulation 65: 561–576PubMedCrossRefGoogle Scholar
  58. 58.
    Fossel ET, Morgan HE, Ingwall JS (1980) Measurements of changes in high energy phosphates in the cardiac cycle by using gated 31 P-nuclear magnetic resonance. Proc Natl Acad Sci USA 77: 3654–3658PubMedCrossRefGoogle Scholar
  59. 59.
    Braunwald E, Kloner RA (1982) The ‘stunned’ myocardium. Circulation 66: 1146–1149PubMedCrossRefGoogle Scholar
  60. 60.
    Geft IL, Fishbein MC, Ninomiya K et al (1982) Intermittent brief periods of ischemia have a cumulative effect and may cause myocardial necrosis. Circulation 66: 1150–1153PubMedCrossRefGoogle Scholar
  61. 61.
    Serruys PW, Wijns W, Grimm J, Slager C, Hess OM (1984) Effects of repeated transluminal occlusion during angioplasty on global and regional left ventricular chamber stiffness. Circulation 70 (Suppl II): 348CrossRefGoogle Scholar
  62. 62.
    Taegtmeyer H, Roberts AFC, Raine AEG (1985) Emergency metabolism in reperfused heart muscle: metabolic correlates to return of function. J Am Coll Cardiol 6: 864–870PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers, Dordrecht 1990

Authors and Affiliations

  • Patrick W. Serruys
  • Federico Piscione
  • William Wijns
  • Johan A. J. Hegge
  • Eef Harmsen
  • Marcel Van Den Brand
  • Pim De Feyter
  • Paul G. Hugenholtz
  • Jan W. De Jong

There are no affiliations available

Personalised recommendations