Thorac Cardiovasc Surg 2002; 50(6): 367-372
DOI: 10.1055/s-2002-35730
Special Report
Original Cardiovascular
© Georg Thieme Verlag Stuttgart · New York

Reduction of Myocardial Reperfusion Injury by High-Dose β-Blockade with Esmolol

H.  J.  Geissler1
  • 1Department of Cardiothoracic Surgery, University of Cologne, Germany
Weitere Informationen

Publikationsverlauf

Received February 19, 2002

Publikationsdatum:
28. November 2002 (online)

Abstract

Background: Myocardial ischemia reperfusion injury may be reduced by β-blockade. However, how myocardial salvage is affected when β-blockade is limited to the reperfusion period is unknown. We investigated the impact of CPB and esmolol during reperfusion on infarct size and left ventricular function in two different experimental models of acute myocardial ischemia. Methods: In open-chest dogs, myocardial ischemia was induced by LAD occlusion in both studies. In study 1, infarct size (TTZ stain) and myocardial water content (MWC, microgravimetry) were determined, comparing reperfusion with blood and esmolol to blood without additives. Study 2 investigated the impact of esmolol on LV function (sonomicrometry, echocardiography) and MWC (microgravimetry) compared to warm blood cardioplegia in a more clinically oriented model. Results: Infarct size and MWC in reperfused myocardium were significantly reduced by esmolol during reperfusion. Global LV function was better preserved in the esmolol group, whereas no difference was seen regarding regional function. Conclusions: Myocardial salvage may be significantly enhanced by CPB and esmolol, even when treatment with esmolol is initiated as late as with the onset of reperfusion.

References

  • 1 Ganote C E. Contraction band necrosis and irreversible myocardial injury.  J Mol Cell Cardiol. 1983;  15 67-73
  • 2 Hansen P R. Role of neutrophils in myocardial ischemia and reperfusion.  Circulation. 1995;  91 1872-1885
  • 3 Badwey J A, Karnovsky M L. Active oxygen species and the functions of phagocytic leukocytes.  Annu Rev Biochem. 1980;  49 695-726
  • 4 Garcia-Dorado D, Theroux P, Munoz R. et al . Favorable effects of hyperosmotic reperfusion on myocardial edema and infarct size.  Am J Physiol. 1992;  262 H17-H22
  • 5 Hoque A N, Nasa Y, Abiko Y. Cardioprotective effect of d-propranolol in ischemic-reperfused isolated rat hearts.  Eur J Pharmacol. 1993;  236 269-277
  • 6 Lange R, Kloner R A, Braunwald E. First ultra-short-acting beta-adrenergic blocking agent: its effect on size and segmental wall dynamics of reperfused myocardial infarcts in dogs.  Am J Cardiol. 1983;  51 1759-1767
  • 7 Laub G W, Muralidharan S, Reibman J. et al . Esmolol and percutaneous cardiopulmonary bypass enhance myocardial salvage during ischemia in a dog model.  J Thorac Cardiovasc Surg. 1996;  111 1085-1091
  • 8 Roth E, Torok B. Effect of the ultrashort-acting beta-blocker Brevibloc on free-radical-mediated injuries during the early reperfusion state.  Basic Res Cardiol. 1991;  86 422-433
  • 9 Roth E, Matos G, Guarnieri C, Papp B, Varga J. Influence of the beta-blocker therapy on neutrophil superoxide generation and platelet aggregation in experimental myocardial ischemia and reflow.  Acta Physiol Hung. 1995;  83 163-170
  • 10 Sidi A, Davis R F. Esmolol decreases the adverse effects of acute coronary artery occlusion on myocardial metabolism and regional myocardial blood flow in dogs.  Anesth Analg. 1988;  67 124-130
  • 11 Sweeney M S, Frazier O H. Device-supported myocardial revascularization: safe help for sick hearts.  Ann Thorac Surg. 1992;  54 1065-1070
  • 12 Mehlhorn U, Allen S J, Adams D L, Davis K L, Gogola G R, Warters R D. Cardiac surgical conditions induced by beta-blockade: effect on myocardial fluid balance.  Ann Thorac Surg. 1996;  62 143-150
  • 13 Geissler H J, Davis K L, Buja L M. et al . Esmolol and cardiopulmonary bypass during reperfusion reduce myocardial infarct size in dogs.  Ann Thorac Surg. 2001;  72 1964-1969
  • 14 Geissler H J, Davis K L, Laine G A. et al . Myocardial protection with high-dose beta-blockade in acute myocardial ischemia.  Eur J Cardiothorac Surg. 2000;  17 63-70
  • 15 Haan C, Lazar H L, Bernard S, Rivers S, Zallnick J, Shemin R J. Superiority of retrograde cardioplegia after acute coronary occlusion.  Ann Thorac Surg. 1991;  51 408-412
  • 16 Axelrod H I, Galloway A C, Murphy M S. et al . A comparison of methods for limiting myocardial infarct expansion during acute reperfusion-primary role of unloading.  Circulation. 1987;  76 V 28-V 32
  • 17 Kukielka G L, Youker K A, Michael L H. et al . Role of early reperfusion in the induction of adhesion molecules and cytokines in previously ischemic myocardium.  Mol Cell Biochem. 1995;  147 5-12
  • 18 Kuhn-Regnier F, Natour E, Dhein S. et al . Beta-blockade versus Buckberg blood-cardioplegia in coronary bypass operation.  Eur J Cardiothorac Surg. 1999;  15 67-74
  • 19 Makiguchi M, Kawaguchi H, Tamura M, Yasuda H. Effect of palmitic acid and fatty acid binding protein on ventricular fibrillation threshold in the perfused rat heart.  Cardiovasc Drugs Ther. 1991;  5 753-761
  • 20 Ferrari R. Myocardial response to reperfusion after a prolonged period of ischemia. 1992: 201
  • 21 Lazar H L, Treanor P, Rivers S, Bernard S, Shemin R J. Combining percutaneous bypass with coronary retroperfusion limits myocardial necrosis.  Ann Thorac Surg. 1995;  59 373-378
  • 22 Laine G A, Allen S J. Left ventricular myocardial edema. Lymph flow, interstitial fibrosis, and cardiac function.  Circ Res. 1991;  68 1713-1721
  • 23 Willerson J T, Scales F, Mukherjee A. et al . Abnormal myocardial fluid retention as an early manifestation of ischemic injury.  Am J Pathol. 1977;  87 159-188
  • 24 Detwiler P W, Nicolosi A C, Weng Z C, Spotnitz H M. Effects of perfusion-induced edema on diastolic stress-strain relations in intact swine papillary muscle.  J Thorac Cardiovasc Surg. 1994;  108 467-476
  • 25 Willerson J T, Powell W J, Jr. , Guiney T E, Stark J J, Sanders C A, Leaf A. Improvement in myocardial function and coronary blood flow in ischemic myocardium after mannitol.  J Clin Invest. 1972;  51 2989-2998
  • 26 Davis K L, Mehlhorn U, Laine G A, Allen S J. Myocardial edema, left ventricular function, and pulmonary hypertension.  J Appl Physiol. 1995;  78 132-137
  • 27 Weng Z C, Nicolosi A C, Detwiler P W. et al . Effects of crystalloid, blood, and University of Wisconsin perfusates on weight, water content, and left ventricular compliance in an edema- prone, isolated porcine heart model.  J Thorac Cardiovasc Surg. 1992;  103 504-513
  • 28 Mehlhorn U, Davis K L, Burke E J, Adams D, Laine G A, Allen S J. Impact of cardiopulmonary bypass and cardioplegic arrest on myocardial lymphatic function.  Am J Physiol. 1995;  268 H178-H183
  • 29 Mehlhorn U, Sauer H, Kuhn-Regnier F. et al . Myocardial beta-blockade as an alternative to cardioplegic arrest during coronary artery surgery.  Cardiovasc Surg. 1999;  7 549-557
  • 30 Pirk J, Kellovsky P. An alternative to cardioplegia.  Ann Thorac Surg. 1995;  60 464-465
  • 31 Pivalizza E G, Sweeney M S. High-dose esmolol and cardiopulmonary bypass for mitral valve replacement in the beating heart.  J Cardiothorac Vasc Anesth. 1997;  11 485-486
  • 32 Matsuda H, Fukushima N, Kadoba K. et al . Application of ultra short acting beta blockade (esmolol) in pediatric open heart surgery: a trial in total anomalous pulmonary venous return.  J Card Surg. 1996;  11 411-415

Dr. med. Hans Joachim Geißler

Klinik für Herz- und Thoraxchirurgie, Universität zu Köln


Joseph-Stelzmann-Straße 9

50924 Köln

Germany

Telefon: +49 (221) 478 41 28

Fax: +49 (221) 478 41 86

eMail: hans.geissler@medizin.uni-koeln.de