Calcium and the Injured Cardiac Myocyte

  • Winifred G. Nayler
  • M. J. Daly
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 34)


Injured cardiac myocytes accumulate Ca2+. It does not seem to matter whether the injury is due to reperfusion after prolonged periods of normothermic ischemia [1, 2], sustained hypoxia [3], a naturally occurring cardiomyopathy, or the reintroduction of Ca2+ after only a few minutes of Ca2+-free perfusion [4–6], the end result is the same—that is, the cells become overloaded with Ca2+. The primary aim of this chapter is to establish why the injured myocytes accumulate Ca2+, and then to define the route by which this Ca2+ enters. Finally we will consider the consequences of the resultant Ca2+ overloading.


Intercalate Disc Ischemic Episode High Energy Phosphate Massive Influx Passive Permeability 
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  1. 1.
    Shen AC, Jennings RB: Myocardial calcium and magnesium in acute ischemic injury. Am J Pathol 67: 417–440, 1972.PubMedGoogle Scholar
  2. 2.
    Nayler WG: The role of calcium in the ischemic myocardium. Am J Pathol 102: 126–134, 1981.Google Scholar
  3. 3.
    Nayler WG, Ferrari R, Poole-Wilson PA, Yepez CE: A protective effect of a mild acidosis on hypoxic heart muscle. J Mol Cell Cardiol 11: 1053–1071, 1979.PubMedCrossRefGoogle Scholar
  4. 4.
    Alto LE, Dhalla NS: Myocardial cation contents during induction of calcium paradox. Am J Physiol 237: H713 - H719, 1979.PubMedGoogle Scholar
  5. 5.
    Nayler WG, Grinwald PM: Dissociation of Ca2+ accumulation from protein release in calcium paradox: effect of barium. Am J Physiol 242: H203 - H210, 1982.PubMedGoogle Scholar
  6. 6.
    Zimmerman ANE, Daems W, Hulsmann WC, Snijder J, Wisse E, Durrer D: Morphological changes of heart muscle caused by successive perfusion with calcium-free and calcium containing solutions (calcium paradox). Cardiovasc Res 1: 201–209, 1967.CrossRefGoogle Scholar
  7. 7.
    Nayler WG: Protection of the myocardium against post ischemic reperfusion damage: the combined effect of hypothermia and nifedipine. J Thorac Cardiovasc Surg, 1982 (in press).Google Scholar
  8. 8.
    Nayler WG, Ferrari R, Williams A: Protective effect of pretreatment with verapamil, nifedipine and propranolol on mitochondrial function in the ischemic and reperfused myocardium. Am J Cardiol 46: 242–248, 1980.PubMedCrossRefGoogle Scholar
  9. 9.
    Bourdillon PD, Poole-Wilson PA: The effects of verapamil, quiescence, and cardioplegia on calcium exchange and mechanical function in ischemic rabbit myocardium. Circ Res 50: 360–368, 1982.PubMedCrossRefGoogle Scholar
  10. 10.
    Peng CF, Kane JJ, Murphy ML, Straub KD: Abnormal mitochondrial oxidative phosphorylation of ischemic myocardium reversed by Caz+-chelating agents. J Mol Cell Cardiol 9: 897–908, 1977.PubMedCrossRefGoogle Scholar
  11. 11.
    Shen AC, Jennings RB: Kinetics of calcium accumulation in acute myocardial ischemic injury. Am J Pathol 67: 441–452, 1972.PubMedGoogle Scholar
  12. 12.
    Shine KI, Douglas AM, Ricchiuti NV: Calcium, strontium, and barium movements during ischemia and reperfusion in rabbit ventricle: implications for myocardial preservation. Circ Res 43: 712–720, 1978.PubMedCrossRefGoogle Scholar
  13. 13.
    Caroni P, Carafoli E: The Caz+-pumping ATPase of heart sarcolemma: characterization, calmodulin dependence, and partial purification. J Biol Chem 256: 3263–3270, 1981.PubMedGoogle Scholar
  14. 14.
    Reuter H: Exchange of calcium ions in the mammalian myocardium: mechanisms and physiological significance. Circ Res 34: 599–605, 1974.PubMedCrossRefGoogle Scholar
  15. 15.
    Langer GA: Sodium-calcium exchange in the heart. Annu Rev Physiol 44: 435–449, 1982.PubMedCrossRefGoogle Scholar
  16. 16.
    Tada M, Yamamoto T, Tonomura Y: Molecular mechanism of active calcium transport by sarcoplasmic reticulum. Physiol Rev 58: 1–79, 1978.PubMedGoogle Scholar
  17. 17.
    Carafoli E, Tiozzo R, Lugli G, Crovetti F, Kratzing C: The release of calcium from heart mitochondria by sodium. J Mol Cell Cardiol 6: 361–371, 1974.PubMedCrossRefGoogle Scholar
  18. 18.
    Jennings RB, Hawkins HK, Lowe JE, Hill ML, Klotman S, Reimer KA: Relation between high energy phosphate and lethal injury in myocardial ischemia in the dog. Am J Pathol 92: 187–214, 1978.PubMedGoogle Scholar
  19. 19.
    Jennings RB, Reimer KA, Hill ML, Mayer SE: Total ischemia in dog hearts, in vivo. 1. Comparison of high energy phosphate production, utilization, and depletion, and of adenine nucleotide catabolism in total ischemia in vivo vs. severe ischemia in vivo. Circ Res 49: 892–900, 1981.PubMedCrossRefGoogle Scholar
  20. 20.
    Jennings RB, Reimer KA: Lethal myocardial ischemic injury. Am J Pathol 102: 241–255, 1981.PubMedGoogle Scholar
  21. 21.
    Reimer KA, Jennings RB, Hill ML: Total ischemia in dog hearts, in vitro. 2. High energy phosphate depletion and associated defects in energy metabolism, cell volume regulation, and sarcolemmal integrity. Circ Res 49: 901–911, 1981.PubMedCrossRefGoogle Scholar
  22. 22.
    Beckman JK, Owens K, Knauer TE, Weglicki WB: Hydrolysis of sarcolemma by lysosomal lipases and inhibition by chlorpromazine. Am J Physiol 242: H652 - H656, 1982.PubMedGoogle Scholar
  23. 23.
    Chien KR, Reeves JP, Buja LM, Bonte F, Parkey RW, Willerson JT: Phospholipid alterations in canine ischemic myocardium: temporal and topographical correlations with Tc-99m-PPi accumulation and an in vitro sarcolemmal Ca2+ permeability defect. Circ Res 48: 711–719, 1981.PubMedCrossRefGoogle Scholar
  24. 24.
    La Noue KF, Watts JA, Koch CD: Adenine nucleotide transport during cardiac ischemia. Am J Physiol 241: H663 - H671, 1981.Google Scholar
  25. 25.
    Dunnett J, Nayler WG: Effect of pH on calcium accumulation and release of isolated fragments of cardiac and skeletal muscle sarcoplasmic reticulum. Biochim Biophys Acta 198: 434–438, 1979.Google Scholar
  26. 26.
    Bersohn MM, Philipson KD, Fukushima JY: Sodium-calcium exchange and sarcolemmal enzymes in ischemic rabbit hearts. Am J Physiol 242: C288 - C295, 1982.PubMedGoogle Scholar
  27. 27.
    Katz AM, Tada M: The “stone heart”: a challenge to the biochemist. Am J Cardiol 29: 578–580, 1972.PubMedCrossRefGoogle Scholar
  28. 28.
    Feher JJ, Briggs FN, Hess ML: Characterization of cardiac sarcoplasmic reticulum from ischemic myocardium: comparison of isolated sarcoplasmic reticulum with unfractionated homogenates. J Mol Cell Cardiol 12: 427–432, 1980.PubMedCrossRefGoogle Scholar
  29. 29.
    Locke FS, Rosenheim O: Contributions to the physiology of the isolated heart: the consumption of dextrose by mammalian cardiac muscle. J Physiol (Lond) 36: 205–220, 1907.Google Scholar
  30. 30.
    Chizzonite RA, Zak R: Calcium-induced cell death: susceptibility of cardiac myocytes is age-dependent. Science 213: 1508–1510, 1981.PubMedCrossRefGoogle Scholar
  31. 31.
    Boink ABTJ, Ruigrok TJ, Zimmerman ANE: Changes in high energy phosphate compounds of isolated rat hearts during Ca2+-free perfusion and re-perfusion with calcium. J Mol Cell Cardiol 8: 973–979, 1976.CrossRefGoogle Scholar
  32. 32.
    Alto LE, Dhalla NS: Role of changes in microsomal calcium uptake in the effects of reperfusion of Caz+deprived rat hearts. Circ Res 48: 17–24, 1981.PubMedCrossRefGoogle Scholar
  33. 33.
    Hearse DJ, Baker JE, Humphrey SM: Verapamil and the calcium paradox. J Mol Cell Cardiol 12: 733–740, 1980.PubMedCrossRefGoogle Scholar
  34. 34.
    Holland CE Jr, Olson RE: Prevention by hypothermia of paradoxical calcium necrosis in cardiac muscle. J Mol Cell Cardiol 7: 917–928, 1975.PubMedCrossRefGoogle Scholar
  35. 35.
    Nayler WG: Cobalt, manganese and the calcium paradox. J Mol Cell Cardiol (Suppl 2 ) 14: 11, 1982.Google Scholar
  36. 36.
    Bielecki K: The influence of changes in pH of the perfusion fluid on the occurrence of the calcium paradox in the isolated rat heart. Cardiovasc Res 3: 268–271, 1969.PubMedCrossRefGoogle Scholar
  37. 37.
    Muir AR: A calcium-induced contracture of cardiac muscle cells. J Anat 102: 148–149, 1968.Google Scholar
  38. 38.
    Crevey BJ, Langer GA, Frank JS: Role of Caz+ in the maintenance of rabbit myocardial cell membrane structural and functional integrity. J Mol Cell Cardiol 10: 1081–1100, 1981.CrossRefGoogle Scholar
  39. 39.
    Grinwald PM, Nayler WG: Calcium entry in the calcium paradox. J Mol Cell Cardiol 3: 867–880, 1981.CrossRefGoogle Scholar
  40. 40.
    Winegrad S, Robinson TF: Force generation among cells in the relaxing heart. Eur J Cardiol (Suppl) 7: 63–70, 1978.Google Scholar
  41. 41.
    Harding DP, Poole-Wilson PA: Calcium exchange in rabbit myocardium during and after hypoxia: effect of temperature and substrate. Cardiovasc Res 14: 435–445, 1980.PubMedCrossRefGoogle Scholar
  42. 42.
    New W, Trautwein W: The ionic nature of slow inward current and its relation to a contraction. Pflugers Arch 334: 24–38, 1972.PubMedCrossRefGoogle Scholar
  43. 43.
    Nayler WG, Thompson JE, Jarrott B: The interaction of calcium antagonists (slow channel inhibitors) with myocardial alpha adrenoceptors. J Mol Cell Cardiol 14: 13–20, 1982.CrossRefGoogle Scholar
  44. 44.
    Krishtal OA, Pidoplichko VI, Shaknovalov Yu A: Conductance of the calcium channel in the membrane of snail neurones. J Physiol 310: 410–434, 1981.Google Scholar
  45. 45.
    Ganote CE, Kaltenbach JP: Oxygen-induced enzyme release: early events and a proposed mechanism. J Mol Cell Cardiol 11: 389–406, 1979.PubMedCrossRefGoogle Scholar
  46. 46.
    Nayler WG, Fassold E, Yepez C: Pharmacological protection of mitochondrial function in hypoxic heart muscle: effect of verapamil, propranolol and methylpridesolone. Cardiovasc Res 12: 152–161, 1978.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media Dordrecht 1984

Authors and Affiliations

  • Winifred G. Nayler
  • M. J. Daly

There are no affiliations available

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