Download PDF
Thorac Cardiovasc Surg 2002; 50(4): 208-215
DOI: 10.1055/s-2002-33091
Original Cardiovascular
Original Paper
© Georg Thieme Verlag Stuttgart · New York

Initial Reperfusion with Magnesium after Cardioplegic Arrest Attenuates Myocardial Reperfusion Injury[*]

F.  Fuchs1 , K.  Messmer1 , H.  Kuppe2 , H.  Habazettl3
  • 1Institute for Surgical Research, Ludwig-Maximilians-Universität München, Germany
  • 2Institute of Anesthesiology, Deutsches Herzzentrum Berlin, Germany
  • 3Department of Physiology, Freie Universität Berlin, Germany
The results from this study were presented in part at the Chirurgische Forschungstage 2000, Marburg, Germany, and at the Annual Meeting of the American Society of Anesthesiologists 2001, New Orleans, USA
Further Information

Publication History

Publication Date:
07 August 2002 (online)

    Permissions and Reprints All articles of this category

Abstract

Background: Magnesium's effect on calcium ion concentrations may attenuate myocardial reperfusion injury. The aim of this study was therefore to investigate the effects on the recovery of myocardial function of initial reperfusion with varying Mg2+ concentrations following cardioplegic arrest. Methods: Isolated guinea pig hearts underwent 3.5 hours of cardioplegic arrest in St. Thomas Hospital II solution (STH) or Bretschneider HTK solution (HTK) at 24° C. Control hearts were reperfused with normal Krebs-Henseleit solution (KHS). In the therapy groups, hearts were initially reperfused with 5, 10, or 20 mM Mg2+ for 15 minutes, followed by 30 minutes of perfusion with KHS. Results: During initial reperfusion, elevated Mg2+ concentrations markedly reduced rate-pressure product, dP/dt and O2 demand. Release of LDH and CK was reduced in the therapy groups pretreated with Bretschneider HTK. After Mg2+ washout, left ventricular function recovery and compliance was improved after HTK but not after STH cardioplegia. Following both STH and HTK cardioplegia, Mg2+ reperfusion reduced reperfusion arrhythmias. Conclusions: The combination of HTK cardioplegia with 15 min initial Mg2+ (5 and 10 mM, but not 20 mM) reperfusion was clearly superior to HTK followed by immediate Krebs-Henseleit reperfusion as well as STH cardioplegia with or without initial Mg2+ reperfusion. The high Mg2+ concentrations in the STH solution might mask beneficial effects of Mg2+ reperfusion.

Key words

Magnesium - Calcium - Reperfusion injury - Cardioplegic solutions

1 The results from this study were presented in part at the Chirurgische Forschungstage 2000, Marburg, Germany, and at the Annual Meeting of the American Society of Anesthesiologists 2001, New Orleans, USA

References

  • 1 Unger F. Open heart surgery in Europe 1993.  Eur J Cardiothorac Surg. 1996;  10 120-128
    CrossrefPubMedGoogle Scholar
  • 2 Piper H M, Garcia-Dorado D, Ovize M. A fresh look at reperfusion injury.  Cardiovasc Res. 1998;  38 291-300
    CrossrefPubMedGoogle Scholar
  • 3 Marban E. Pathogenetic role for calcium in stunning.  Cardiovasc Drugs Therap. 1991;  5 891-894
    PubMedGoogle Scholar
  • 4 Opie L H. Postischemic stunning - the case for calcium as the ultimate culprit.  Cardiovasc Drugs Therap. 1991;  5 895-899
    PubMedGoogle Scholar
  • 5 Opie L H, du Toit E F. Postischemic stunning: the two-phase model for the role of calcium as pathogen.  J Cardiovasc Pharmacol. 1992;  20 (Suppl 5) S1-S4
    PubMedGoogle Scholar
  • 6 Kimura Y, Engelman R M, Rousou J, Flack J, Iyengar J, Das D K. Moderation of myocardial ischemia reperfusion injury by calcium channel and calmodulin receptor inhibition.  Heart Vessels. 1992;  7 189-195
    CrossrefPubMedGoogle Scholar
  • 7 Hintze T H, Vatner S F. Comparison of effects of nifedipine and nitroglycerin on large and small coronary arteries and cardiac function in conscious dogs.  Circ Res. 1983;  52 139-146
    PubMedGoogle Scholar
  • 8 Habazettl H, Voigtländer J, Leiderer R, Messmer K. Efficacy of myocardial initial reperfusion with 2,3 butanedione monoxime after cardioplegic arrest is time-dependent.  Cardiovasc Res. 1998;  37 684-690
    CrossrefPubMedGoogle Scholar
  • 9 Voigtländer J, Leiderer R, Mühlbayer D, Habazettl H. Release of cytosolic enzymes and troponin I vs. ultrastructural damage of isolated hearts after initial reperfusion with 2,3 butanedione monoxime (BDM).  Thorac Cardiovasc Surg. 1999;  47 244-250
    PubMedGoogle Scholar
  • 10 Kotsanas G, Holroyd S M, Wendt I R, Gibbs C L. Intracellular Ca2+ force and activation of heart in rabbit papillary muscle: effects of 2,3-butanedione monoxime.  J Mol Cell Cardiol. 1993;  25 1349-1358
    CrossrefPubMedGoogle Scholar
  • 11 Jager B V, Stagg G N. Toxicity of diacetyl monoxime and of pyridine-2-aldoxime methiodide in man.  Bull Johns Hopkins Hosp. 1958;  102 203-214
    PubMedGoogle Scholar
  • 12 Hearse D J, Stewart D A, Baimbridge M V. Myocardial protection during ischemic cardiac arrest. The importance of magnesium in cardioplegic infusates.  J Thorac Cardiovasc Surg. 1978;  75 877-885
    PubMedGoogle Scholar
  • 13 Tzivoni D, Banai S, Benhorin J, Keren A, Gottlieb S, Stern S. Treatment of torsade de pointes with magnesium sulfate.  Circulation. 1988;  77 392-397
    CrossrefPubMedGoogle Scholar
  • 14 Zumino A P, Baiardi G, Schanne O F, Petrich E R. Differential electrophysiologic effects of global and regional ischemia and reperfusion in perfused rat hearts. Effects of Mg2+ concentration.  Mol Cell Biochem. 1998;  186 79-86
    CrossrefPubMedGoogle Scholar
  • 15 Bersohn M M, Shine K I, Sterman W D. Effect of increased magnesium on recovery from ischemia in rat and rabbit hearts.  Am J Physiol. 1982;  242 H89-H93
    PubMedGoogle Scholar
  • 16 Isiri L T, French J H. Magnesium: nature's physiologic calcium blocker.  Am Heart J. 1984;  108 188-193
    CrossrefPubMedGoogle Scholar
  • 17 Silverman H S, Di-Lisa F D, Hui R C. et al . Regulation of intracellular free Magnesium and contraction in single mammalian cardiac myocytes.  Am J Physiol. 1994;  266 C222-C233
    PubMedGoogle Scholar
  • 18 Agus Z A, Kellepouris E, Dukes I, Morad M. Cytosolic magnesium modulates calcium channel activity in mammalian ventricular cells.  Am J Physiol. 1989;  256 C452-C455
    PubMedGoogle Scholar
  • 19 Barbour R L, Altura B M, Reiner S D. et al . Influence of Mg2+ on cardiac performance, intracellular free Mg2+, and pH in perfused hearts as assesed with 31P nuclear magnetic resonance spectroscopy.  Magnesium Trace Elem. 1992;  10 99-116
    PubMedGoogle Scholar
  • 20 Headrick J P, McKirdy J C, Willis R J. Functional and metabolic effects of extracellular magnesium in normoxic and ischemic myocardium.  Am J Physiol. 1998;  275 H917-H929
    PubMedGoogle Scholar
  • 21 Terada H, Hayashi H, Noda N, Satoh H, Katoh H, Yamazaki N. Effects of Mg2+ on Ca2+ waves and Ca2+ transients of rat ventricular myocytes.  Am J Physiol. 1996;  270 H907-H914
    PubMedGoogle Scholar
  • 22 Habazettl H, Palmisano B W, Bosnjak Z J, Stowe D F. Initial 2,3-butanedione monoxime reperfusion is superior to hyperkalemic warm cardioplegic reperfusion in the isolated guinea pig heart.  Eur J Cardio-thorac Surg. 1996;  10 897-904
    CrossrefPubMedGoogle Scholar
  • 23 Holm S. A simple sequentially rejective multiple test procedure.  Scand J Stat. 1979;  6 65-70
    PubMedGoogle Scholar
  • 24 Piper H M, Garcia-Dorado D. Prime causes of rapid cardiomyocyte death during reperfusion.  Ann Thorac Surg. 1999;  68 1913-1919
    CrossrefPubMedGoogle Scholar
  • 25 Kukreja R C, Janin Y. Reperfusion injury: basic concepts and protection strategies.  J Thromb Thrombolysis. 1997;  4 7-24
    CrossrefPubMedGoogle Scholar
  • 26 MacLeod D, MacLeod J. Magnesium: physiology and pharmacology.  Br J Anaesth. 1999;  83 972-973
    PubMedGoogle Scholar
  • 27 McCord J M. Oxygen-derived free radicals in postischemic tissue injury.  N Engl J Med. 1985;  312 159-163
    PubMedGoogle Scholar
  • 28 White R E, Hartzell H C. Effects of intracellular free magnesium on calcium current in isolated cardiac myocytes.  Science. 1988;  239 778-780
    PubMedGoogle Scholar
  • 29 Hall S K, Fry C H. Magnesium affects excitation, conduction, and contraction of isolated mammalian cardiac muscle.  Am J Physiol. 1992;  263 H622-H633
    PubMedGoogle Scholar
  • 30 Saks V A, Chernousova G B, Gukovsky D E, Smirnov V N, Chazov E I. Studies of energy transport in heart cells. Mitochondrial isoenzyme of creatine phosphokinase: kinetic properties and regulatory actions of Mg2+ ions.  Eur J Biochem. 1975;  57 273-290
    CrossrefPubMedGoogle Scholar
  • 31 Tsukube T, McCully J D, Faulk E A. et al . Magnesium cardioplegia reduces cytosolic and nuclear calcium and DNA fragmentation in the senescent myocardium.  Ann Thorac Surg. 1994;  58 1005-1011
    PubMedGoogle Scholar
  • 32 Fabiato A, Fabiato F. Effects of magnesium on contractile activation of skinned cardiac cells.  J Physiol. 1975;  249 497-517
    PubMedGoogle Scholar
  • 33 Dickens B F, Weglicki W B, Li Y S, Mak I T. Magnesium deficiency in vitro enhances free radical-induced intracellular oxidation and cytotoxicity in endothelial cells.  FEBS Lett. 1992;  311 187-191
    CrossrefPubMedGoogle Scholar
  • 34 Garcia L A, Dejong S C, Martin S M, Smith R S, Buettner G R, Kerber R E. Magnesium reduces free radicals in an in vivo coronary occlusion-reperfusion model.  Am Coll Cardiol. 1998;  32 536-539
    PubMedGoogle Scholar
  • 35 Buckberg G D. Phases of myocardial protection during transplantation.  J Thorac Cardiovasc Surg. 1990;  100 461-462
    PubMedGoogle Scholar
  • 36 Ferrier G R, Moffat M P, Lukas A. Possible mechanisms of ventricular arrhythmias elicited by ischemia followed by reperfusion.  Circ Res. 1985;  56 184-194
    PubMedGoogle Scholar
  • 37 Hayashi H, Ponnambalam C, McDonald T F. Arrhythmic activity in reoxygenated guinea pig papillary muscles and ventricular cells.  Circ Res. 1987;  61 124-133
    PubMedGoogle Scholar

1 The results from this study were presented in part at the Chirurgische Forschungstage 2000, Marburg, Germany, and at the Annual Meeting of the American Society of Anesthesiologists 2001, New Orleans, USA

Helmut Habazettl

Department of Physiology, Freie Universität Berlin

Arnimallee 22

14195 Berlin

Germany

Phone: +49 (30) 8445-1638

Fax: +49 (30) 8445-1634

Email: habazett@zedat.fu-berlin.de