Organ Protection with ATP-Magnesium Chloride

  • James M. Harkema
  • Irshad H. Chaudry
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 181)


The heart and other organs are dependent on aerobic metabolism. When the arterial blood flow is reduced to the point that insufficient oxygen is available for oxidative phosphorylation, the production of adenosine triphosphate (ATP) is decreased. This reduction in ATP occurs at a time when more energy is needed to protect the cell against injury. Thus, since ATP plays an essential role in numerous cellular functions, it is not surprising that ischemia and hypovolemic shock produce alterations in cellular and subcellular function in the heart and other organs (1,2). Indeed, the resynthesis of ATP is a major rate-limiting factor following hypovolemic shock and ischemia (3,4). Very low levels of ATP are invariably associated with the irreversible state following myocardial ischemia (5,6). Thus, despite attempts to restore adequate tissue perfusion, including oxygen and substrates, there is a failure to replenish and regenerate ATP during such conditions. This results in persistent and progressive cellular injury that can progress to organ failure. Therefore, replenishing cellular energy following ischemia and hypovolemic shock has been one of a variety of different strategies that have been investigated to prevent or minimize cell injury. Moreover, the most direct approach for raising ATP levels under these conditions appears to be the infusion of ATP rather than the administration of substrates and/or agents that would synthesize it.


Hemorrhagic Shock Adenine Nucleotide Creatine Phosphate Myocardial Oxygen Consumption Hypovolemic Shock 
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.
    Jennings RB, Steenberg C, Jr: Nucleotide metabolism and cellular damage in myocardial ischemia. Ann Rev Physiol 1985;47:727–749.Google Scholar
  2. 2.
    Chaudry IH: Cellular mechanisms in shock and ischemia and their correction. Am J Physiol 1983;245: R117–R143.PubMedGoogle Scholar
  3. 3.
    Chaudry IH, Baue AE: The use of substrates and energy in the treatment of shock. In: Advances in Shock Research, Lefer AM, Saba TM, Mela LM, Eds. New York: Alan R. Liss, 1980; Vol. 3, 27–46.Google Scholar
  4. 4.
    Swain JL, Sabina RL, McHale PA, Greenfield JC, Jr., Holmes EW: Prolonged myocardial nucleotide depletion after brief ischemia in the open-chest dog. Am J Physiol 1982; 242: H818–H826.PubMedGoogle Scholar
  5. 5.
    Braunwald E, Kloner RA: The stunned myocardium: Prolonged, post-ischemic ventricular dysfunction. Circulation 1982;66: 1146–1149.PubMedGoogle Scholar
  6. 6.
    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 1978;92: 187–214.PubMedGoogle Scholar
  7. 7.
    Parratt JR, Marshall RJ: The response of isolated cardiac muscle to acute anoxia: Protective effects of adenosine triphosphate and creatine phosphate. J Pharm Pharmacol 1973;26: 427–433.Google Scholar
  8. 8.
    Hearse DJ, Stewart DA, Braimbridge MV: Myocardial protection during bypass and arrest. J Thorac Cardiovasc Surg 1976;72: 880–884.PubMedGoogle Scholar
  9. 9.
    Talaat SM, Mission WH, Schilling JA: Effects of adenosine triphosphate administration in reversible hemorrhagic shock. Surgery 1964;55: 813–819.PubMedGoogle Scholar
  10. 10.
    Sharma GP, Eiseman B: Protective effect of ATP in experimental shock. Surgery 1966;59: 66–75.PubMedGoogle Scholar
  11. 11.
    Chaudry IH, Clemens MG, Baue AE: The role of ATP-magnesium in ischemia and shock. Magnesium 1986;5:211–220.PubMedGoogle Scholar
  12. 12.
    Altura BM, Altura BT: Magnesium and vascular tone and reactivity. Blood Vessels 1978;15: 5–16.PubMedGoogle Scholar
  13. 13.
    Turlapaty PDMV, Altura BM: Extracellular magnesium ions control calcium exchange and contents of vascular smooth muscle. Eur J Pharmacol 1978;52: 421–423.PubMedGoogle Scholar
  14. 14.
    Altura BM, Altura BT, Gebrewold A, Ising H, Gunther T: Magnesium deficiency of hypertension: Correlation between magnesium deficient diets of microcirculatory changes in situ. Science 1984;223: 1315–1317.PubMedGoogle Scholar
  15. 15.
    Seelig MS, Heggtvert HA: Magnesium interrelationships in ischemic heart disease: A review. Am J Clin Nutr 1974;27: 59–79.PubMedGoogle Scholar
  16. 16.
    Turlapaty PDMV, Altura BM: Magnesium deficiency produces spasms of coronary arteries: Relationship to etiology of sudden death ischemic heart disease. Science l980; 208:198–200.Google Scholar
  17. 17.
    Hearse DJ: Cardioplegia: The protection of the myocardium during open heart surgery: A review. J Physiol 1980;76: 751–768.Google Scholar
  18. 18.
    Baue AE, Chaudry IH, Wurth MA, Sayeed MM: Cellular alterations with shock and ischemia. Angiology 1974; 25: 31–41.PubMedGoogle Scholar
  19. 19.
    Chaudry IH: Use of ATP following shock and ischemia. Ann NY Acad Sci 1990;603: 130–141.PubMedGoogle Scholar
  20. 20.
    Harkema JM, Chaudry IH: Magnesium-adenosine triphosphate in the treatment of shock, ischemia, and sepsis. Crit Care Med 1992;20: 263–274.PubMedGoogle Scholar
  21. 21.
    McCord JM: Free radicals and myocardial ischemia: Overview and outlook. Free Radie Biol Med 1988;4: 9–14.Google Scholar
  22. 22.
    Lucchesi BR: Myocardial ischemia, reperfusion and free radical injury. Am J Cardiol 1990;65: 141–231.Google Scholar
  23. 23.
    Lucchesi BR: Complement activation, neutrophils, and oxygen radicals in reperfusion injury. Stroke (Supp I) 1993;24: 141–149.Google Scholar
  24. 24.
    Korthius RJ, Grisham MB, Zimmerman BJ, Granger DN, Taylor AE: Vascular injury in dogs during ischemia-reperfusion: Improvement with ATP-MgCl2 pretreatment. Am J Physiol 1988;254: H702–H708.Google Scholar
  25. 25.
    Hsu K, Wang D, Wu S, Shen C, Chen HI: Ischemia-reperfusion lung injury attenuated by ATP-MgCl2 in rats. J Appl Physiol 1994;76: 545–552.PubMedGoogle Scholar
  26. 26.
    Vary TC, Reibel DK, Neely JR: Control of energy metabolism of heart muscle. Ann Rev Physiol 1981;43: 419–430.Google Scholar
  27. 27.
    Hinkle PC, McCarty RE: How cells make ATP. Sci Am 1978, 238: 104–124.PubMedGoogle Scholar
  28. 28.
    Neely JR, Morgan HE: Relationship between carbohydrate and lipid metabolism and energy balance of the heart. Ann Rev Physiol 1999; 36: 413–459.Google Scholar
  29. 29.
    Kobayashi K, Neely JR: Control of maximum rates of glycolysis in rat cardiac muscle. Circ Res 1979;44: 166–175.PubMedGoogle Scholar
  30. 30.
    Williamson JR: Mitochondrial metabolism and cell regulation. In: Mitochondria: Bioenergetics, Biogenesis and Membrane Structure. Packer L, Gomes-Poyon A, Eds. New York: Academic Press, 1976;79–107.Google Scholar
  31. 31.
    Hatifi Y: The mitochondrial electron transport and oxidative phosphorylation system. Ann Rev Biochem 1985;54: 1015–1061.Google Scholar
  32. 32.
    Mathews PM, Bland JL, Gadian DG, Radda GK The steady-state rate of ATP synthesis in the perfused rat heart measured by 31P NMR saturation transfer. Biochem Biophys Res Commun 1981;103:1052–1059.Google Scholar
  33. 33.
    Williamson JR: Mitochondrial function in the heart. Ann Rev Physiol 1979;41: 485–506.Google Scholar
  34. 34.
    Kubier W, Spreckermann PG: Changes in glycolysis and in high energy phosphates during myocardial ischemia with intermittent coronary perfusion. Cardiology 1971;56: 100–107.Google Scholar
  35. 35.
    Piper J, DuPrangsero PE, Cerretilli P: Oxygen debt and high energy phosphates in gastrocnemius muscle of the dog. Am J Physiol 1968;215: 523–525.Google Scholar
  36. 36.
    Rovetto MJ, Lamberton WF, Neely JR: Mechanism of glycolytic inhibition in ischemic rat hearts. Circ Res 1975;37: 742–751.PubMedGoogle Scholar
  37. 37.
    Atkinson DE: The energy charge of the adenylate pool as a regulator parameter interaction with feedback modifiers. Biochem 1966;17: 4030–4034.Google Scholar
  38. 38.
    Crowell JW, Jones CE, Smith EE: Effect of allopurinol on hemorrhagic shock. Am J Physiol 1969;216: 215–221.Google Scholar
  39. 39.
    Cunningham SK, Keaveny TM: The splanchnic organ adenine nucleotides and their metabolites in hemorrhagic shock. Ir J Med Sci 1977;146: 136–143.PubMedGoogle Scholar
  40. 40.
    Horpascy G, Schnells G: metabolism of adenine nucleotides in the kidney during hemorrhagic hypotension and after recovery. J Surg Res 1980;29: 11–17.Google Scholar
  41. 41.
    Kovâch AGB, Bagdy D, Balâzs R, Antoni F, Gergley J, Menyhârt J, Irani M Kovâch E: Traumatic shock and adenosine triphosphate. Acta Physiol Hung 1952;3: 331–334.Google Scholar
  42. 42.
    Zaki MS, Burke JL, Tralstad R: Protective effects of adenosine-triphosphate administration in burns. Arch Surg 1978;113: 605–610.PubMedGoogle Scholar
  43. 43.
    Chaudry IH, Sayeed MM, Baue AE: Alterations in high energy phosphate in hemorrhagic shock as related to tissue and organ function. Surgery 1976;79: 666–668.PubMedGoogle Scholar
  44. 44.
    LePage GA: Biological energy transformation during shock as shown by tissue analysis. Am J Physiol 1946;146: 267–281.PubMedGoogle Scholar
  45. 45.
    Chaudry IH, Sayeed MM, Baue AE: Effect of hemorrhagic shock on tissue adenine nucleotides in conscious rats. Can J Physiol Pharmacol 1974;52: 131–137.PubMedGoogle Scholar
  46. 46.
    Warnick CT, Lazarus HM: Recovery of nucleotide levels after cell injury. Canad J Biochem 181;59: 116–121.Google Scholar
  47. 47.
    Kamiike W, Watanabe F, Hashimoto T, Tagawa K, Ikeda Y, Nakao K, Kawashima Y: Changes in cellular levels of ATP and its catabolites in ischemic rat liver J Biochem 1982;91: 1349–1356.PubMedGoogle Scholar
  48. 48.
    Farber E: ATP and cell integrity. Fed Proc 1973;32: 1534–1539.PubMedGoogle Scholar
  49. 49.
    Rovetto MJ, Whitmer JT, Neely JR: Comparison of effects of anoxia and whole heart ischemia on carbohydrate utilization in isolated working rat heart. Circ Res 1973 32:699–711.PubMedGoogle Scholar
  50. 50.
    Braasch W, Gudbjarmason S, Puri PS, Ravens KG, Bing RJ: Early changes in energy metabolism in the myocardium following acute coronary artery occlusion in anesthetized dogs. Circ Res 1968;23: 429–438.PubMedGoogle Scholar
  51. 51.
    Boyer PH, Chance B, Ernester L, Mitchell P, Racher E, Slater EC: Oxidative phosphorylation and photophosphorylation. Ann Rev Biochem 1977;46: 955–1026.PubMedGoogle Scholar
  52. 52.
    Harden WR, Barlow CH, Simson MB, Harken AH: Temporal relationship between onset of cell anoxia and ischemic contractile function. Am J Cardiol 1979;44: 741–746.PubMedGoogle Scholar
  53. 53.
    Hearse DJ: Oxygen deprivation at early myocardial failure: A reassessment of the possible role of adenosine triphosphate. Am J Cardiol 1979;44: 1115–1121.PubMedGoogle Scholar
  54. 54.
    Wechsler AS, Abd-Elfattah AS, Murphy CE, Salter DR, Brunsting LA, Goldstein JP: Myocardial protection. J Cardiovasc Surg 1986;1:271–306.Google Scholar
  55. 55.
    Abd-Elfattah AS, Slater DR, Murphy CE, Goldstein JP, Brunsting CA, Wechsler AS: Metabolic differences between retrograde and antegrade cardioplegia after reversible normothermic global ischemic injury. Surg Forum 1986;37: 267–270.Google Scholar
  56. 56.
    Swain JL, Holmes EW: Nucleotide metabolism in cardiac muscle: In: Fozzard HA, Haber E, Jennings RB, Katz A, Morgan HE (eds): The Heart and Cardiovascular System. New York, Raven Press, 1986;911–929.Google Scholar
  57. 57.
    Wechsler AS, Saiter DR, Murphy CE, Goldstein JP, Brunsting LA Abd-Elfattah AS: Metabolic differences of retrograde cardioplegia: In: Mole W, Faxon D, Wolner E (eds): Clinics of CSI. New York, Steinkupff-Verlag Dramsadt, 1986;181–187.Google Scholar
  58. 58.
    Imais S, Riley AL, Berne RM: Effect of ischemia on adenine nucleotides in cardiac and skeletal muscle. Circ Res 1964;15:443–450.Google Scholar
  59. 59.
    Schrader J, Gerlach E: Compartmentation of cardiac adenine nucleotides and formation of adenosine. Pfleregers Arch 1976;367:129–135.Google Scholar
  60. 60.
    Reibel DK, Rovetto MJ: Myocardial adenosine salvage rates and restoration of ATP content following ischemia. Am J Physiol 1979;237: H247-H252.PubMedGoogle Scholar
  61. 61.
    Schutz W, Schrader J, Gerlach E: Different sites of adenosine formation in the heart. Am J Physiol 181;240: H963–H970.Google Scholar
  62. 62.
    Liu MS, Feinberg H: Incorporation of adenosine-8- C and inosine-8- C into rabbit heart adenine nucleotides. Am J Physiol 1971;220: 1242–1248.PubMedGoogle Scholar
  63. 63.
    Reibel DK, Rovetto MJ: Myocardial ATP synthesis and mechanical function following oxygen deficiency. Am J Physiol 1978;234:H620–H624.PubMedGoogle Scholar
  64. 64.
    Vary TC, Angelakos ET, Schaffer SW: Relationship between adenine nucleotide metabolism and irreversible ischemic tissue damage in isolated perfused rat heart. Circ Res 1979;45: 218–225.PubMedGoogle Scholar
  65. 65.
    Zimmer HG, Tredelenburg C, Kammermeier H, Gerlach E: De novo synthesis of myocardial nucleotides in the rat. Circ Res 1973;32:635–642.PubMedGoogle Scholar
  66. 66.
    Reimer KA, Hill ML, Jennings RB: Prolonged depletion of ATP and the adenine nucleotide pool due to delayed resynthesis of adenine nucleotides following reversible myocardial ischemic injury in dogs. J Mol Cell Cardiol 1981;13:229–239.PubMedGoogle Scholar
  67. 67.
    Crowell JW, Smith EE: Oxygen deficit and irreversible hemorrhagic shock. Am J Physiol 1964; 206: 313–316.PubMedGoogle Scholar
  68. 68.
    Swast CJ, Rowlands SD: Oxygen consumption and hepatic metabolism in experimental posthemorrhagic shock. J Trauma 1972;12:327–334.Google Scholar
  69. 69.
    Baue AE, Wurth MA, Sayeed MM: The dynamics of altered ATP-dependent and ATP-yielding cell process in shock. Surgery 1972;72:94–101.PubMedGoogle Scholar
  70. 70.
    Kleber AG: Resting membrane potential, extracellular potassium activity, and intracellular sodium activity during global warm ischemia in perfused guinea pig hearts. Circ Res 1983;52:442–450.PubMedGoogle Scholar
  71. 71.
    Weil MH, Afiffi MA: Experimental and clinical studies on lactate and pyruvate and indicators of the severity of acute circulatory failure (shock). Circulation 1970;41:989–1001.PubMedGoogle Scholar
  72. 72.
    Peretz DI, Cett HM, Duff J: The significance of lactic acidemia in the shock syndrome. Ann NY Acad Sci 1965;119: 1133–1141.PubMedGoogle Scholar
  73. 73.
    Schumer W: Localization of energy pathway block in shock. Surgery 1968;64: 55–59.PubMedGoogle Scholar
  74. 74.
    Whitmer JT, Idell-Wenger JA, Rovetto MJ, Neely JR: Control of fatty acid metabolism in ischemic and hypoxic hearts. J Biol Chan 1978;253: 4305–4309.Google Scholar
  75. 75.
    Chaudry IH, Harkema JM, Dean RE: Alterations in energy production: A manifestation of cell injury. In: New Horizons: Multiple Organ Failure. Bihari DJ, Cerra IB, Eds. Fullerton, CA: The Society of Critical Care Medicine, 1989.Google Scholar
  76. 76.
    Rhodes RS, DePalma ER: Mitochondrial dysfunction of the liver and hypoglycemia in hemorrhagic shock. Surg Gyn Obstet 1980;1560: 347–352.Google Scholar
  77. 77.
    Mela L: Mitochondrial function in shock, ischemia and hypoxia. In: Pathophysiology of Shock, Anoxia and Ischemia, Crowley RA, Trump BF, Eds. Baltimore: Williams and Wilkins, 1982;84–95.Google Scholar
  78. 78.
    Hift H, Shawitz JG: Irreversible shock in dogs: Structure and function of liver mitochondria. Am J Physiol 1961;200: 264–268.PubMedGoogle Scholar
  79. 79.
    Schaper J, Hehrlein F, Schlepper M, Thredemann U: Ultrastructural alterations during ischemia and reperfusion in human hearts during cardiac surgery. J Mol Cell Cardiology 1977;9: 175–180.Google Scholar
  80. 80.
    Loiselle J, Denstedt OD: Biological changes during acute physiological failure in the rat. II. The behavior of adenine and pyridine nucleotides of the liver during shock. Can J Biochem 1964;42:21–25.Google Scholar
  81. 81.
    Sayeed MM, Baue AE: Mitochondrial metabolism of succinate, β-Miydroxybutyrate and α-ketoglutarate in hemorrhagic shock. Am J Physiol 1971;220: 1275–1281.PubMedGoogle Scholar
  82. 82.
    Greenwalk JW, Rossi CS, Lehninger AL: Effect of active accumulation of calcium and phosphate ions on the structure and function of rat liver mitochondria. J Cell Biol 1964;23: 21–25.Google Scholar
  83. 83.
    Jennings RB: Calcium ions in ischemia. In: Calcium Antagonists and Cardiovascular Disease, Opie LH, Ed. New York: Raven Press, 1984;85–95.Google Scholar
  84. 84.
    Farber JL: Biology of disease: Membrane injury and calcium homeostasis in the pathogenesis of coagulative necrosis. Lab Invest 1982;47:114–123.PubMedGoogle Scholar
  85. 85.
    Chaudry IH, Ohkawa M, Clemens MG: Improved mitochondrial Ca2+ homeostasis and phosphorylative capability by ATP-MgCl2 following ischemia (abstract). Circ Shock 1982;9: 175.Google Scholar
  86. 86.
    Chaudry IH, Ohkawa M. Clemens MG: Improved mitochondrial function following ischemia and reflow by ATP-MgCl2. Am J Physiol 1984;246:R799–R804.PubMedGoogle Scholar
  87. 87.
    Chaudry IH, Ohkawa M, Clemens MG: Alterations in electron transport and cellular metabolism in shock and trauma. In: Molecular and Cellular Aspects of Shock and Trauma, Lefer AM, Shumer W, Eds. New York: Alan R. Liss, 1983;67–83.Google Scholar
  88. 88.
    Swain JL, Hines JJ, Sabina RL, Holmes EW: Accelerated repletion of ATP and GTP pools in postishemic canine myocardium using a precursor of purine de novo synthesis. Circ Res 1982;51: 102–105.PubMedGoogle Scholar
  89. 89.
    Abd-Elfattah AS, Jessen ME, Hanan SA, Tuchy E, Wechsler AS: Is adenosine 5′-triphosphate derangement or free-radical-mediated injury the major cause of ventricular dysfunction during reperfusion? Role of adenine nucleoside transport in myocardial reperfusion injury. Circ 1990;82(Suppl IV):IV341–IV350.Google Scholar
  90. 90.
    Abd-Elfattah AS, Jessen ME, Lekven J, Doherty NE III, Brunsting LA, Wechsler AS: Myocardial reperfusion injury. Role of myocardial hypoxanthine and xanthine in free radicalmediated reperfusion injury. Circ 1988;78(Suppl III):III224–III235.Google Scholar
  91. 91.
    Van Rossum GD: The relation of sodium and potassium ion transport to respiration and adenine nucleotide content of liver slices treated with inhibitors of respiration. Biochem J 1992;129: 427–438.Google Scholar
  92. 92.
    Vogt MT, Fraber E: The effects of ethionine treatment of the metabolism of liver mitochondria. Arch Biochem Biophys 1970;141:162–173.PubMedGoogle Scholar
  93. 93.
    Chaudry IH, Sayeed MM, Baue AE: Effect of adenosine triphosphate-magnesium chloride administration in shock. Surgery 1974;75:220–227.PubMedGoogle Scholar
  94. 94.
    Furchgott RF, Gubareff T: High energy phosphate content of cardiac muscle under various experimental conditions which alter contractility. J Pharm Exp Ther 1958;124:203–218.Google Scholar
  95. 95.
    Williamson JR (1966): Glycolytic function control mechanisms. II. Kinetics of intermediate changes during the aerobic-anoxic transition in perfused rat heart. J Biol Chem 1966;241: 5026–5036.PubMedGoogle Scholar
  96. 96.
    Hearse DJ, Garlick PB, Humphrey SM: Ischemic contracture of the myocardium: mechanism and prevention. Am J Cardiol 1971;39:986–993.Google Scholar
  97. 97.
    Donaldson SKB, Bond E, Seeger L, Niles N, Bolles L: Intracellular pH vs MgATP concentration: Relative importance as determinants of Ca-activated force generation of disrupted rabbit cardiac cells. Cardiovasc Res 1981;15:268–275.PubMedGoogle Scholar
  98. 98.
    McClellan GB, Winegrad S: The regulation of the calcium sensitivity of the contractile system in mammalian cardiac muscle. J Gen Physiol 1978;72: 737–764.PubMedGoogle Scholar
  99. 99.
    Kammermeier H, Schmidt P, Tungling E: Free energy changes of ATP hydrolysis: A causal factor of early hypoxic failure of the myocardium? J Mol Cell Cardiol 1982;14:267–277.PubMedGoogle Scholar
  100. 100.
    Weiner JM, Apstein CS, Arthur JH, Pirzada H, Hood WB: Persistence of myocardial injury following brief periods of coronary occlusion. Cardiovasc Res 1976;10:678–686.PubMedGoogle Scholar
  101. 101.
    Murphy SM, Halliss DE, Seelye RN: Myocardial adenine pool depletion and recovery of myocardial function following ischemia. Am J Physiol 1985;248: H644–H651.Google Scholar
  102. 102.
    Neely JR, Grotyohann LW: Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate level and recovery of function of reperfused ischemic heart. Circ Res 1984;55:816–824.PubMedGoogle Scholar
  103. 103.
    Katz AM, Hecht HH: The early pump failure of the ischemic heart. Am J Med 1969;47: 497–502.PubMedGoogle Scholar
  104. 104.
    Liedtke AJ, Nellis S, Neely JR: Effects of excess free fatty acids on mechanical and metabolic function in normal and ischemic myocardium in swine. Circ Res 1978;43:652–661.PubMedGoogle Scholar
  105. 105.
    Burger R, Lowenstein JM: Adenylate deaminase. J Biol Chem 1976; 242:5281–5288.Google Scholar
  106. 106.
    Pine MB, Kahne D, Taski B, Apstein CS, Thorp K, Abelmann WH: Sodium permeability and myocardial resistance to cell swelling during metabolic blockade. Am J Physiol 1980;239:H31–H39.PubMedGoogle Scholar
  107. 107.
    Jennings RB, Steenbergen C, Jr., Kenney RB, Hill ML, Reimer KA: Comparison of the effect of ischemia and anoxia on the sarcolemma of the dog heart. Eur Heart J 1983;4(Suppl): 123–137.PubMedGoogle Scholar
  108. 108.
    Shires GT, Cunningham JN, Backer CR, Reeder SF, Illner H, Wagner IY, Maher J: Alterations in cellular membrane function during hemorrhagic shock in primates. Ann Surg 1872;176:288–294.Google Scholar
  109. 109.
    Chapman RA: Control of cardiac contractility at the cellular level. Am J Physiol 1983;245:H535–H552.PubMedGoogle Scholar
  110. 110.
    Lee HC, Smith N, Mohaber R, Clusin WT: Cytosolic calcium transients from the beating mammalian heart. Proc Natl Acad Sci USA 1987;84:7793–7798.PubMedGoogle Scholar
  111. 111.
    Morris AC, Hagler HK, Buja LM: Relationship between calcium loading and impaired energy metabolism during Na+, K+ inhibition and metabolic inhibition in cultured neonatal rat cardiac myocytes. J Clin Invest 1989;83:1876–1881.PubMedGoogle Scholar
  112. 112.
    Lindberg BH, Haljamae HB, Jonsson O, Pettersson S: Effect of glucagon and blood transfusion on liver metabolism in hemorrhagic shock. Ann Surg 1987;187:103–109.Google Scholar
  113. 113.
    Sayeed MM: Membrane sodium-potassium transport and ancillary phenomenon in circulatory shock. In: Pathophysiology of Shock, Anoxia and Ischemia, Cowley RA, Trump BF, Eds. Baltimore: Williams and Wilkins, 1988;112–132.Google Scholar
  114. 114.
    Sayeed MM, Wurth MA, Chaudry IH, Baue AE: Cation transport in the liver in hemorrhagic shock. Circ Shock 1974;1:195–207.Google Scholar
  115. 115.
    Holliday RL, Illner HP, Shires GT: Liver cell membrane alterations during hemorrhagic shock in the rat. J Surg Res 1981;31:506–515.PubMedGoogle Scholar
  116. 116.
    Jennische E: Immediate effects of hemorrhage on the hepatic cell membrane potential in the rat. Acta Physiol Scand 1981;112:343–344.PubMedGoogle Scholar
  117. 117.
    Sayeed MM, Alder RF, Chaudry IH, Baue AE: Resting membrane potential and ion distribution in the liver in hemorrhagic shock. Am J Physiol 1981;240:R211–R219.PubMedGoogle Scholar
  118. 118.
    Wang P, Hauptman JG, Chaudry IH: Hepatocellular dysfunction occurs early after hemorrhage and persists despite fluid resuscitation. J Surg Res 1990;48:464–470.PubMedGoogle Scholar
  119. 119.
    Ohkawa M, Clemens MG, Chaudry IH: Studies on the mechanism of beneficial effects of ATP-MgCl2 following hepatic ischemia. Am J Physiol 1983;244:R695–R702.PubMedGoogle Scholar
  120. 120.
    Chaudry IH, Stephan RN, Dean RE, Clemens MC, Baue AE: Use of Magnesium-ATP following liver ischemia. Magnesium 1988;7:68–77.PubMedGoogle Scholar
  121. 121.
    Chaudry IH, Stephan RN, Harkema JM Dean RE: Immunological alterations following simple hemorrhage. In: Immune Consequences of Trauma, Shock and Sepsis: Mechanisms and Therapeutic Approaches, Faist E, Ninnemann J, Green D, Eds. Berlin: Springer-Verlag, 1989;363–373.Google Scholar
  122. 122.
    Weisfeldt ML: Reperfusion and reperfusion injury. Clin Res 1987;35:13–20.PubMedGoogle Scholar
  123. 123.
    Jennings RB, Reimer KA: Factors involved in salvaging ischemic myocardium: Effect of reperfusion of arterial blood. Circulation 1983;68(Suppl):I125–I136.Google Scholar
  124. 124.
    Werms SW, Shea MJ, Lucchesi BR: Free radicals in ischemic myocardial injury. Free Radie Biol Med 1985;1:103–110.Google Scholar
  125. 125.
    Jolly SR, Kane WJ, Bailie MB, Abrams GD, Lucchesi BR: Canine myocardial reperfusion injury. Its reduction by the combined administration of superoxide dismutase and catalase. Circ Res 1984;54:277–285.PubMedGoogle Scholar
  126. 126.
    DiStazio J, Maley WE, Thompson S, Thompson B, Sembrat R, Stremple J: Effect of ATP-MgCl2-glucose administration during hemorrhagic shock on cardiac metabolism, function and survival. In: Advances in Shock Research, Lefer AM, Suba TM, Mela LM, Eds. New York: Alan R. Liss,190;3:153–166.Google Scholar
  127. 127.
    Hirasawa H, Oda S, Hayashi H, Ohtake Y, Odaka M, Sato H: Improved survival and reticuloendothelial function with intravenous ATP-MgCl2 following hemorrhagic shock. Circ Shock 1983;11:141–148.PubMedGoogle Scholar
  128. 128.
    Kraven T, Rush RF, Ghosh A, Adams-Griffin M: Improved survival and metabolic changes in a rat shock model produced by ATP-MgCl2 Curr Surg 1979;36:435–437.PubMedGoogle Scholar
  129. 129.
    Chaudry IH, Hirasawa H, Baue AE: Effect of adenosine triphosphate-glucose administration following sepsis. J Surg Res 1980;29:348–356.PubMedGoogle Scholar
  130. 130.
    Hirasawa H, Chaudry IH, Baue AE: Improved hepatic function and survival with adenosine triphosphate-magnesium chloride after hepatic ischemia. Surgery 1978;83:655–662.PubMedGoogle Scholar
  131. 131.
    Hirasawa H, Ohkawa M, Odaka M, Sato H: Improved survival, RES function and ICG clearance tests with ATP-MgCl2 following hepatic ischemia. Surg Forum 1979;30:158–160.PubMedGoogle Scholar
  132. 132.
    Cikrit D, Gross K, Katz S, Plager D, Ross D, Wolfe M, Weber TR, Grosfeld JL: Comparative effects of cytoprotective agents in bowel ischemia. Surg Forum 1983;34: 208–210.Google Scholar
  133. 133.
    Fulton RL: Prevention of endotoxin death with nicotinamide and adenosine triphosphate. Surg Forum 1974;25: 17–19.PubMedGoogle Scholar
  134. 134.
    Filkins JP, Buchanan BJ: Protection against endotoxin shock and impaired glucose homeostasis with ATP. Circ Shock 1977;4:253–258.PubMedGoogle Scholar
  135. 135.
    Klay JW, Chaudry IH, Geha AS, Baue AE: Improved myocardial performance with infusion of adenosine-triphosphate-MgCl2 Surg Forum 1980;31:260–262.Google Scholar
  136. 136.
    McGovern PJ, Jr., Rush BF, Machiedo GW, Kraven T: ATP-MgCl2 improves cardiac output aftershock. Surg Forum 1981;32:1–3.Google Scholar
  137. 137.
    Wang P, Ba ZF, Chaudry IF: ATP-MgCl2 restores the depressed cardiac output following trauma and severe hemorrhage even in the absence of blood resuscitation. Circ Shock 1992;36:277–283.PubMedGoogle Scholar
  138. 138.
    Wang P, Chaudry IH: Crystalloid resuscitation restores but does not maintain cardiac output following severe hemorrhage. J Surg Res 1991;50:163–169.PubMedGoogle Scholar
  139. 139.
    McDonagh PF, Laks H, Chaudry IH, Baue AE: Improved myocardial recovery from ischemia. Treatment with low-dose adenosine triphosphate-magnesium chloride. Arch Surg 1984;119: 1378–1384.Google Scholar
  140. 140.
    Kopf G, Chaudry IH, Condos S, Baue AE: Improved myocardial performance following prolonged ischemia with ATP-MgCl2 cardioplegia. Surg Forum 1986;37:234–236.Google Scholar
  141. 141.
    Kopf G, Chaudry IH, Condos S, Baue AE: Reperfusion with ATP-MgCl2 following prolonged ischemia improves myocardial performance. J Surg Res 1986;43:114–117.Google Scholar
  142. 142.
    Cohen MV, Sonnenblick EH, Kirk ES: Coronary steal: Its role in the detrimental effect of isoproterenol after acute coronary occlusion in dogs. Am J Cardiol 1976;38:880–888.PubMedGoogle Scholar
  143. 143.
    Lytton B, Vaisbort VR, Glazier WB, Chaudry IH, Baue AE: Improved renal function using ATP-MgCl2 in preservation of canine kidneys subjected to warm ischemia. Transplantation 1981;31:187–189.PubMedGoogle Scholar
  144. 144.
    Osias MB, Siegel NJ, Chaudry IH, Lytton B, Baue AE: Postischemic renal failure. Accelerated recovery with adenosine triphosphate-magnesium chloride infusion. Arch Surg 1977;112:729–731.PubMedGoogle Scholar
  145. 145.
    Andrews PM, Coffey AK: Protection of kidneys from acute renal failure resulting from normothermic ischemia. Lab Invest 1983;49:87–98.PubMedGoogle Scholar
  146. 146.
    Sumpio BE, Hull MJ, Baue AE, Chaudry IH: Comparison of effects of ATP-MgCl2 and Adenosine-MgCl2 on renal function following ischemia. Am J Physiol 1987;252:R388–R393.PubMedGoogle Scholar
  147. 147.
    Sumpio BE, Chaudry IH, Baue AE: Adenosine triphosphate-magnesium chloride ameliorates reperfusion injury following ischemia is determined by phosphorous nuclear magnetic resonance. Arch Surg 1985;120:233–240.PubMedGoogle Scholar
  148. 148.
    Chaudry IH, Clemens MG, Ohkawa M, Schleck S, Baue AE: Restoration of hepatocellular function and blood flow following ischemia with ATP-MgCl2. Adv Shock Res 1982;8:177–186.PubMedGoogle Scholar
  149. 149.
    Boss WK, Fusi S, Chaudry IH, Clemens MG, Chater C, Laub D, Jr., Cuono CB, Ariyan S: Improved skin flap survival with adenosine triphosphate-magnesium chloride. Surg Forum 1984;35: 576–578.Google Scholar
  150. 150.
    Cikrit D, Billmore D, Lopex MR, West KW, Grosfeld JL, Smith D: Beneficial effects of exogenous adenosine triphosphate on skin flap viability. Surg Forum 1984;35:578–580.Google Scholar
  151. 151.
    Chaudry IH, Gould MK: Evidence for the uptake of ATP by rat soleus muscle in vitro. Biochim Biophys Acta 1970;196:320–326.PubMedGoogle Scholar
  152. 152.
    Kraven T, Rush B, Slotman GJ, Adams-Griffin M: Permeability of the shock cell to ATP-MgCl2. Surg Forum 1970;30:7–9.Google Scholar
  153. 153.
    Machiedo GW, Ghuman S, Rush BF, Kraven T, Dikdan G: The effect of ATP-MgCl2 infusion on hepatic cell permeability and metabolism following hemorrhagic shock. Surgery 1981;90:328–335.PubMedGoogle Scholar
  154. 154.
    Pant HC, Terakawa S, Yoshioki T, Tasaki I, Gainer H: Evidence for the utilization of extracellular [γ-32P]ATP for the phosphorylation of intracellular proteins in the squid giant axon. Biochim Biophys Acta 1979;582:107–114.PubMedGoogle Scholar
  155. 155.
    Maxild J: Effect of externally added ATP and related compounds on active transport of p- aminohippurate and metabolism in Cortisol slices of the rabbit kidney. Arch Int Physiol Biochem 1978;86:509–530.Google Scholar
  156. 156.
    Williams D, Rubel D, Rovetlo MJ: ATP induced increase in ATP content of cultured myocardial cells (abstract). Fed Proc 1979;38:1389.Google Scholar
  157. 157.
    Ziegelhoffer A, Fedelesova M, Kostolansky S: Special ATP action on the metabolism of isolated heart: Influence of pH, divalent cation concentration and stability of complexes. Acta Biol Med Germ 1972;28:893–900.PubMedGoogle Scholar
  158. 158.
    Chien KR, Reeves JP, Buja M, 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. Clin Res 1981;48: 711–719.Google Scholar
  159. 159.
    Otani H, Prasad MR, Engelman RM, Otani H, Cordis GA, Das DK Enhanced phosphodiesteratic breakdown and turnover of phosphoinositides during reperfusion of ischemic rat heart. Circ Res 1988;63:930–936.PubMedGoogle Scholar
  160. 160.
    Jellinek M, Shapiro M, Abdulla R, Vellareal-Loor B, Standeven J, Baue A Effect of ATP and/or inositol on glucose release by the liver in rabbits with hemorrhagic shock (abstract). Circ Shock 1989;27:312.Google Scholar
  161. 161.
    Shapiro MJ, Jellinek M, Chardel B, Chandel B, Tadros C, Baue AE: Improved survival from hemorrhagic shock with inositol and ATP-MgCl2 administration (abstract). Circ Shocle l989;2T. 361.Google Scholar
  162. 162.
    Wang P, Ba ZB, Dean RE, Chaudry IH: ATP-MgCl2 restores the depressed hepatocellular function following hemorrhage and resuscitation. J Surg Res 1991;50:368–374.PubMedGoogle Scholar
  163. 163.
    Wang P, Ba ZF, Morrison MS, Ayala A, Dean RE, Chaudry IH: Mechanism of the beneficial effects of ATP-MgC2 following trauma-hemorrhage and resuscitation: Downregulation of inflammatory cytokine (TNF, IL-6) release. J Surg Res 1992;52:364–371.PubMedGoogle Scholar
  164. 164.
    Paumgartner G, Probst G, Kraines R, Leevy CM: Kinetics of indocyanine green removal from the blood. Ann NY Acad Sci 1970;170:134–143.Google Scholar
  165. 165.
    Hirasawa H, Ohkawa M, Kobayashi H, Odakh M, Sato H: Reversal of ischemic reinduced hepatic cellular edema by administration of ATP-MgCl2 Surg Forum 1980;31:10–12.Google Scholar
  166. 166.
    Ohkawa M, Chaudry IH, Clemens MG, Baue AE: Improvement in water and electrolyte homeostasis by ATP-MgC2 after ischemia (abstract). Circ Shock 1982;9:162–163.Google Scholar
  167. 167.
    Chaudry IH, Sayeed MM, Baue AE: Insulin resistance and its reversal by in vivo infusion of ATP in hemorrhagic shock. Can J Physiol Pharm 1976;54:736–741.Google Scholar
  168. 168.
    Kloner RA, Ganote CE, Jennings RB (1974): The “no flow” phenomenon after temporary coronary occlusion in the dog. J Clin Invest 54: 1496–1508.PubMedGoogle Scholar
  169. 169.
    Clemens MG, Chaudry IH, Baue AE: Increased coronary flow and myocardial efficiency with systemic infusion of ATP-MgCl2 Surg Forum 1985;36:244–246.Google Scholar
  170. 170.
    Wohlgelernter D, Jaffe C, Clemen M, Young L, Clemens MG, Chaudry IH: Effects of ATP-MgCl2 on coronary blood flow and myocardial oxygen consumption (abstract). Circulation 1985;72(III): 315.Google Scholar
  171. 171.
    Wang P, Zhou M, Rana MW, Singh G, Ba ZF, Ayala A, Chaudry IH. ATP-MgCl2 restores renal microcirculation following trauma and severe hemorrhage. Can J Physiol Pharmacol 1992, 70: 349–357.PubMedGoogle Scholar
  172. 172.
    Chaudry IH: ATP-MgCl2, and liver blood flow following shock and ischemia. In: Progress in Clinical and Biological Research. Perspectives in Shock Research, Metabolism, Immunology, Mediators and Model, Passmore JC, Reichard SM, Reynolds DC, Traber DE, Eds. New York: Alan R. Liss, 1989;299:19–31.Google Scholar
  173. 173.
    Fox AD, Chaudry IH, Kupper TS, Green DR, Clemens MG, Baue AE: Restoration of the depressed immune response after burn injury by administration of ATP-MgCl2 or Tuftsin. Surg Forum 1982;33:69–71.Google Scholar
  174. 174.
    Chaudry IH, Tabata Y, Schleck S, Baue AE: Impairment of reticuloendothelial function following hepatic ischemia and its restoration with ATP-MgCl2 administration. Adv Shock Res 1980;3:219–228.Google Scholar
  175. 175.
    Chaudry IH, Hirasawa H, Baue AE: Impairment of reticuloendothelial system function with sepsis and its improvement with ATP-MgC2 administration. Adv Shock Res 1979;2:153–162.PubMedGoogle Scholar
  176. 176.
    Meldrum DR, Ayala A, Wang P, Ertel W, Chaudry IH: Association between decreased splenic ATP levels and immunodepression: amelioration with ATP-MgCl2. Am J Physiol 1991;261:R351–R357.PubMedGoogle Scholar
  177. 177.
    Meldrum DR, Ayala A, Chaudry IH: Energetics of defective macrophage antigen presentation after hemorrhage as determined by Ultraresolution P nuclear magnetic resonance spectrometry: Restoration with adenosine triphosphate-MgCl2 Surgery 1992;112:150–156.PubMedGoogle Scholar
  178. 178.
    Chaudry IH, Keefer JR, Barash P, Clemens MF, Kopf E, Baue AE: ATP-MgCl2 infusion in man: Increased cardiac output without adverse systemic hemodynamic effects. Surg Forum 1984;35: 13–15.Google Scholar
  179. 179.
    Hirasawa H, Soeda K, Ohkawa M, Kobayashi N, Murotani N, Odaka M, Sato H (1985): A randomized clinical trial on ATP-MgCl2 for post-ischemic acute renal failure (abstract). Circ Shock 1985;13:66.Google Scholar
  180. 180.
    Hirasawa HT, Sugai T, Ohtake Y: Effect of impaired hepatic mitochondrial function (HMF) on systemic metabolism in multiple organ function (MOF) in patients and its treatment with ATP-MgCl2 (abstract). Circ Shock 1989;27:361.Google Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • James M. Harkema
    • 1
  • Irshad H. Chaudry
    • 1
    • 2
  1. 1.Shock and Trauma Research Institute, Department of SurgeryMichigan State UniversityEast LansingUSA
  2. 2.Shock and Trauma Research Institute, Department of PhysiologyMichigan State UniversityEast LansingUSA

Personalised recommendations