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DOI: 10.1055/s-2002-33091
© Georg Thieme Verlag Stuttgart · New York
Initial Reperfusion with Magnesium after Cardioplegic Arrest Attenuates Myocardial Reperfusion Injury[*]
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, USAPublication History
Publication Date:
07 August 2002 (online)
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
- 2 Piper H M, Garcia-Dorado D, Ovize M. A fresh look at reperfusion injury. Cardiovasc Res. 1998; 38 291-300
- 3 Marban E. Pathogenetic role for calcium in stunning. Cardiovasc Drugs Therap. 1991; 5 891-894
- 4 Opie L H. Postischemic stunning - the case for calcium as the ultimate culprit. Cardiovasc Drugs Therap. 1991; 5 895-899
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 16 Isiri L T, French J H. Magnesium: nature's physiologic calcium blocker. Am Heart J. 1984; 108 188-193
- 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
- 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
- 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
- 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
- 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
- 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
- 23 Holm S. A simple sequentially rejective multiple test procedure. Scand J Stat. 1979; 6 65-70
- 24 Piper H M, Garcia-Dorado D. Prime causes of rapid cardiomyocyte death during reperfusion. Ann Thorac Surg. 1999; 68 1913-1919
- 25 Kukreja R C, Janin Y. Reperfusion injury: basic concepts and protection strategies. J Thromb Thrombolysis. 1997; 4 7-24
- 26 MacLeod D, MacLeod J. Magnesium: physiology and pharmacology. Br J Anaesth. 1999; 83 972-973
- 27 McCord J M. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med. 1985; 312 159-163
- 28 White R E, Hartzell H C. Effects of intracellular free magnesium on calcium current in isolated cardiac myocytes. Science. 1988; 239 778-780
- 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
- 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
- 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
- 32 Fabiato A, Fabiato F. Effects of magnesium on contractile activation of skinned cardiac cells. J Physiol. 1975; 249 497-517
- 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
- 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
- 35 Buckberg G D. Phases of myocardial protection during transplantation. J Thorac Cardiovasc Surg. 1990; 100 461-462
- 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
- 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
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