Thorac Cardiovasc Surg
DOI: 10.1055/s-0043-1772210
Original Basic Science

Myocardial Recovery, Metabolism, and Structure after Cardiac Arrest with Cardioplexol

Carina Hemmerich
1   Department of Cardiovascular Surgery, University Hospitals Giessen and Marburg Campus Giessen, Giessen, Germany
,
Martina Heep
1   Department of Cardiovascular Surgery, University Hospitals Giessen and Marburg Campus Giessen, Giessen, Germany
,
Ulrich Gärtner
2   Institute of Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University Giessen, Giessen, Germany
,
Zulfugar Timur Taghiyev
1   Department of Cardiovascular Surgery, University Hospitals Giessen and Marburg Campus Giessen, Giessen, Germany
,
Matthias Schneider
3   Medical and Forensic Veterinary Clinic, Department of Small Animal Internal Medicine, Justus-Liebig-University of Giessen, Giessen, Germany
,
Andreas Böning
1   Department of Cardiovascular Surgery, University Hospitals Giessen and Marburg Campus Giessen, Giessen, Germany
4   Department of Cardiovascular Surgery, University Hospital Giessen, Giessen, Giessen, Germany
› Author Affiliations

Abstract

Objectives Clinical studies indicate encouraging cardioprotective potential for Cardioplexol. Its cardioprotective capacities during 45 minutes of ischemia compared with pure no-flow ischemia or during 90 minutes of ischemia compared with Calafiore cardioplegia were investigated experimentally.

Methods Forty-four rat hearts were isolated and inserted into a blood-perfused pressure-controlled Langendorff apparatus. In a first step, cardiac arrest was induced by Cardioplexol or pure no-flow ischemia lasting 45 minutes. In a second step, cardiac arrest was induced by Cardioplexol or Calafiore cardioplegia lasting 90 minutes. For both experimental steps, cardiac function, metabolic parameters, and troponin I levels were evaluated during 90 minutes of reperfusion. At the end of reperfusion, hearts were fixed, and ultrastructural integrity was examined by electron microscopy.

Results Step 1: after 90 minutes of reperfusion, hearts exposed to Cardioplexol had significantly higher left ventricular developed pressure (CP-45ˊ: 74%BL vs. no-flow-45ˊ: 45%BL; p = 0.046) and significantly better maximal left ventricular relaxation (CP-45ˊ: 84%BL vs. no-flow-45ˊ: 51%BL; p = 0.012). Oxygen consumption, lactate production, and troponin levels were similar in both groups. Step 2: left ventricular developed pressure was lower (22 vs. 48% of BL; p = 0.001) and coronary flow was lower (24 vs. 53% of BL; p = 0.002) when Cardioplexol was used compared with Calafiore cardioplegia. Troponin I levels were significantly higher under Cardioplexol (358.9 vs. 106.1 ng/mL; p = 0.016).

Conclusion Cardioplexol significantly improves functional recovery after 45 minutes of ischemia compared with pure ischemia. However, Cardioplexol protects the myocardium from ischemia/reperfusion-related damage after 90 minutes of ischemia worse than Calafiore cardioplegia.

Presentation at Scientific Meetings

Preliminary results have been presented at the annual meeting of the DGTHG in February 2021. Additionally, results have been presented at the annual meeting of the DGTHG in February 2023.




Publication History

Received: 23 May 2023

Accepted: 10 July 2023

Article published online:
10 August 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Tevaeara Stahel H, Barandun S, Kaufmann E. et al. Single-center experience with the combination of Cardioplexol™ cardioplegia and MiECC for isolated coronary artery bypass graft procedures. J Thorac Dis 2019; 11 (Suppl. 10) S1471-S1479
  • 2 Tschopp S, Eckstein F, Matt P. Low-volume cardioplegia and myocardial protection in coronary artery bypass graft surgery. Thorac Cardiovasc Surg 2019; 67 (06) 484-487
  • 3 Matt P, Arbeleaz E, Schwirtz G, Doebele T, Eckstein F. Low-volume, single-shot crystalloid cardioplegia is safe for isolated aortic valve replacement. Thorac Cardiovasc Surg 2012; 60 (05) 360-362
  • 4 Kairet K, Deen J, Vernieuwe L, De Bruyn A, Kalantary S, Rodrigus I. Cardioplexol, a new cardioplegic solution for elective CABG. J Cardiothorac Surg 2013; 8: 120
  • 5 Moh'd AF, Al-Odwan HT, Altarabsheh S, Makahleh ZM, Khasawneh MA. Predictors of aortic clamp time duration and intensive care unit length of stay in elective adult cardiac surgery. Egypt Heart J 2021; 73 (01) 92
  • 6 Koechlin L, Zenklusen U, Doebele T. et al. Clinical implementation of a novel myocardial protection pathway in coronary artery bypass surgery with minimal extracorporeal circulation. Perfusion 2019; 34 (04) 277-284
  • 7 Koechlin L, Rrahmani B, Gahl B. et al. Microplegia versus Cardioplexol® in coronary artery bypass surgery with minimal extracorporeal circulation: comparison of two cardioplegia concepts. Thorac Cardiovasc Surg 2020; 68 (03) 223-231
  • 8 Böning A, Hagmüller S, Heep M, Rohrbach S, Niemann B, Mühlfeld C. Is warm or cold Calafiore blood cardioplegia better? Hemodynamic, metabolic, and electron microscopic differences. Thorac Cardiovasc Surg 2014; 62 (08) 683-689
  • 9 Böning A, Rohrbach S, Kohlhepp L. et al. Differences in ischemic damage between young and old hearts–Effects of blood cardioplegia. Exp Gerontol 2015; 67: 3-8
  • 10 Follath F, Cleland JGF, Just H. et al; Steering Committee and Investigators of the Levosimendan Infusion versus Dobutamine (LIDO) Study. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet 2002; 360 (9328) 196-202
  • 11 Mühlfeld C, Nyengaard JR, Mayhew TM. A review of state-of-the-art stereology for better quantitative 3D morphology in cardiac research. Cardiovasc Pathol 2010; 19 (02) 65-82
  • 12 DiBona DR, Powell Jr WJ. Quantitative correlation between cell swelling and necrosis in myocardial ischemia in dogs. Circ Res 1980; 47 (05) 653-665
  • 13 Mühlfeld C, Richter J. High-pressure freezing and freeze substitution of rat myocardium for immunogold labeling of connexin 43. Anat Rec A Discov Mol Cell Evol Biol 2006; 288 (10) 1059-1067
  • 14 Schmiedl A, Schnabel PA, Mall G. et al. The surface to volume ratio of mitochondria, a suitable parameter for evaluating mitochondrial swelling. Correlations during the course of myocardial global ischaemia. Virchows Arch A Pathol Anat Histopathol 1990; 416 (04) 305-315
  • 15 Doughty RN, Klein AL, Poppe KK. et al; Meta-analysis Research Group in Echocardiography (MeRGE) Heart Failure Collaborators. Independence of restrictive filling pattern and LV ejection fraction with mortality in heart failure: an individual patient meta-analysis. Eur J Heart Fail 2008; 10 (08) 786-792
  • 16 Metkus TS, Suarez-Pierre A, Crawford TC. et al. Diastolic dysfunction is common and predicts outcome after cardiac surgery. J Cardiothorac Surg 2018; 13 (01) 67
  • 17 Garcia-Dorado D, Andres-Villarreal M, Ruiz-Meana M, Inserte J, Barba I. Myocardial edema: a translational view. J Mol Cell Cardiol 2012; 52 (05) 931-939
  • 18 Laine GA, Allen SJ. Left ventricular myocardial edema. Lymph flow, interstitial fibrosis, and cardiac function. Circ Res 1991; 68 (06) 1713-1721
  • 19 Desai KV, Laine GA, Stewart RH. et al. Mechanics of the left ventricular myocardial interstitium: effects of acute and chronic myocardial edema. Am J Physiol Heart Circ Physiol 2008; 294 (06) H2428-H2434
  • 20 Jennings RB, Sommers HM, Kaltenbach JP, West JJ. Electrolyte alterations in acute myocardial ischemic injury. Circ Res 1964; 14: 260-269
  • 21 Inserte J, Garcia-Dorado D, Ruiz-Meana M, Solares J, Soler J. The role of Na+-H+ exchange occurring during hypoxia in the genesis of reoxygenation-induced myocardial oedema. J Mol Cell Cardiol 1997; 29 (04) 1167-1175
  • 22 Hearse DJ, Garlick PB, Humphrey SM. Ischemic contracture of the myocardium: mechanisms and prevention. Am J Cardiol 1977; 39 (07) 986-993
  • 23 Kingsley PB, Sako EY, Yang MQ. et al. Ischemic contracture begins when anaerobic glycolysis stops: a 31P-NMR study of isolated rat hearts. Am J Physiol 1991; 261 (2, Pt 2): H469-H478
  • 24 Grossman W, Barry WH. Diastolic pressure-volume relations in the diseased heart. Fed Proc 1980; 39 (02) 148-155
  • 25 Humphrey SM, Gavin JB, Herdson PB. The relationship of ischemic contracture of vascular reperfusion in the isolated rat heart. J Mol Cell Cardiol 1980; 12 (12) 1397-1406
  • 26 Flameng W, Lesaffre E, Vanhaecke J. Determinants of infarct size in non-human primates. Basic Res Cardiol 1990; 85 (04) 392-403
  • 27 Reimer KA, Vander Heide RS, Richard VJ. Reperfusion in acute myocardial infarction: effect of timing and modulating factors in experimental models. Am J Cardiol 1993; 72 (19) 13G-21G
  • 28 Garcia-Dorado D, Théroux P, Elizaga J. et al. Myocardial reperfusion in the pig heart model: infarct size and duration of coronary occlusion. Cardiovasc Res 1987; 21 (07) 537-544
  • 29 Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Ischemia/reperfusion. Compr Physiol 2016; 7 (01) 113-170
  • 30 Jennings RB, Schaper J, Hill ML, Steenbergen Jr C, Reimer KA. Effect of reperfusion late in the phase of reversible ischemic injury. Changes in cell volume, electrolytes, metabolites, and ultrastructure. Circ Res 1985; 56 (02) 262-278
  • 31 Chambers DJ, Fallouh HB. Cardioplegia and cardiac surgery: pharmacological arrest and cardioprotection during global ischemia and reperfusion. Pharmacol Ther 2010; 127 (01) 41-52
  • 32 Bell RM, Mocanu MM, Yellon DM. Retrograde heart perfusion: the Langendorff technique of isolated heart perfusion. J Mol Cell Cardiol 2011; 50 (06) 940-950