Experimental Comparison of Esmolol- and Blood-Based Cardioplegia for Long Aortic Clamping Times

Abstract

Objectives

After cardiac surgery, long aortic clamping times and extracorporeal circulation times are associated with worse outcomes. This study compares hemodynamic performance, myocardial metabolism, and ultrastructural preservation in rat hearts after applying esmolol crystalloid cardioplegia (ECCP) or Calafiore blood cardioplegia (Cala).

Materials and Methods

Hearts from 18 Wistar rats were perfused in a Langendorff system. Following 120 minutes of ischemia at 36 °C, hearts received either ECCP at 32 °C for 3 minutes or Cala at 36 °C for 2 minutes every 20 minutes. During 90 minutes of reperfusion, coronary blood flow (CF), left ventricular developed pressure (LVDP), and contraction/relaxation velocities (±dp/dt) were recorded. Myocardial oxygen consumption, lactate production, and troponin I levels were measured. Electron microscopy was used for ultrastructural assessment.

Results

Baseline (BL) values of LVDP, CF, and ±dp/dt were similar between the two groups. After 90 minutes of reperfusion, CF was significantly higher in the ECCP group: 85 ± 43% of BL in the ECCP group versus 42 ± 24% of BL in the Cala group (p = 0.002). At the end of reperfusion, hearts exposed to ECCP had higher LVDP (91 ± 40%) values than Cala (43 ± 10%), indicating improved cardiac recovery with ECCP. Myocardial contraction and relaxation were notably better in the ECCP group: dLVP/dt_max was 111 ± 40% versus 59 ± 13% in the Cala group (p = 0.002), and dLVP/dt_min was 88 ± 34% versus 40 ± 7% (p = 0.001). Troponin I levels measured in Cala hearts at the end of reperfusion were higher than in ECCP hearts (Cala 1,102.6 ± 361.3 ng/mL vs. ECCP 442.3 ± 788.4 ng/mL, p = 0.036).

Conclusion

In rat hearts, ECCP offers better hemodynamic recovery and protects the myocardium from ischemia/reperfusion-related damage, better than Cala blood cardioplegia, even with aortic clamping times of 120 minutes.

Keywords

esmolol cardioplegia - blood cardioplegia - myocardial protection - ischemia–reperfusion injury

Note

This study was presented at the 53rd annual meeting of the German Society of Thoracic and Cardiovascular Surgery, 18 February 2024, Hamburg, Germany.

Data Availability Statement

The data underlying this manuscript will be shared by the corresponding author upon reasonable request.

Authors' Contribution

A.B. contributed to conceptualization; data curation; acquisition of study; investigation; methodology; supervision; validation; visualization; writing—original draft. B.C. contributed to data—collection, validation, and curation; formal analysis; writing—review and editing. M.H. contributed to data—collection, validation, and curation; formal analysis. U.G. contributed to conceptualization; project administration; data curation; investigation; methodology; supervision; validation; writing—review and editing. B.N. contributed to supervision; writing—review and editing. Z.T.T. contributed to data curation; formal analysis; data validation; visualization; writing—review and editing.

Publication History

Received: 06 February 2025

Accepted: 20 May 2025

Accepted Manuscript online:
22 May 2025

Article published online:
10 June 2025

• References

• 1 Calafiore AM, Teodori G, Mezzetti A. et al. Intermittent antegrade warm blood cardioplegia. Ann Thorac Surg 1995; 59 (02) 398-402
• 2 Calafiore AM, Teodori G, Bosco G. et al. Intermittent antegrade warm blood cardioplegia in aortic valve replacement. J Card Surg 1996; 11 (05) 348-354
• 3 Maruyama Y, Chambers DJ, Ochi M. Future perspective of cardioplegic protection in cardiac surgery. J Nippon Med Sch 2013; 80 (05) 328-341
• 4 Chambers DJ. Mechanisms and alternative methods of achieving cardiac arrest. Ann Thorac Surg 2003; 75 (02) S661-S666
• 5 Fallouh HB, Kentish JC, Chambers DJ. Targeting for cardioplegia: arresting agents and their safety. Curr Opin Pharmacol 2009; 9 (02) 220-226
• 6 Veitinger AB, Komguem A, Assling-Simon L. et al. Cardioprotection with esmolol-based cardioplegia for non-infarcted and infarcted rat hearts. Eur J Cardiothorac Surg 2021; 60 (04) 908-917
• 7 Jucá FG, Freitas FL, Goncharov M. et al. Difference between cardiopulmonary bypass time and aortic cross-clamping time as a predictor of complications after coronary artery bypass grafting. Braz J Cardiovasc Surg 2024; 39 (02) e20230104
• 8 Conzelmann LO, Weigang E, Mehlhorn U. et al.; GERAADA Investigators. Mortality in patients with acute aortic dissection type A: analysis of pre- and intraoperative risk factors from the German Registry for Acute Aortic Dissection Type A (GERAADA). Eur J Cardiothorac Surg 2016; 49 (02) e44-e52
• 9 Doenst T, Borger MA, Weisel RD, Yau TM, Maganti M, Rao V. Relation between aortic cross-clamp time and mortality–not as straightforward as expected. Eur J Cardiothorac Surg 2008; 33 (04) 660-665
• 10 Hemmerich C, Heep M, Gärtner U, Taghiyev ZT, Schneider M, Böning A. Myocardial recovery, metabolism, and structure after cardiac arrest with Cardioplexol. Thorac Cardiovasc Surg 2023; ( E-pub ahead of print)
• 11 Böning A, Menzebach S, Heep M. et al. Calafiore cardioplegia offers better myocardial protection in adult and senescent rat hearts than Del Nido cardioplegia. Perfusion 2024; 39 (08) 1605-1613
• 12 Nishina D, Chambers DJ. Efficacy of esmolol cardioplegia during hypothermic ischaemia. Eur J Cardiothorac Surg 2018; 53 (02) 392-399
• 13 Melendez JA, Stone JG, Delphin E, Quon CY. Influence of temperature on in vitro metabolism of esmolol. J Cardiothorac Anesth 1990; 4 (06) 704-706
• 14 Jacobs JR, Croughwell ND, Goodman DK, White WD, Reves JG. Effect of hypothermia and sampling site on blood esmolol concentrations. J Clin Pharmacol 1993; 33 (04) 360-365
• 15 Cork RC, Kramer TH, Dreischmeier B, Behr S, DiNardo JA. The effect of esmolol given during cardiopulmonary bypass. Anesth Analg 1995; 80 (01) 28-40
• 16 Bessho R, Chambers DJ. Myocardial protection with oxygenated esmolol cardioplegia during prolonged normothermic ischemia in the rat. J Thorac Cardiovasc Surg 2002; 124 (02) 340-351
• 17 Boening A, Hinke M, Heep M, Boengler K, Niemann B, Grieshaber P. Cardiac surgery in acute myocardial infarction: crystalloid versus blood cardioplegia - an experimental study. J Cardiothorac Surg 2020; 15 (01) 4
• 18 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
• 19 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
• 20 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
• 21 Fallouh HB, Bardswell SC, McLatchie LM, Shattock MJ, Chambers DJ, Kentish JC. Esmolol cardioplegia: the cellular mechanism of diastolic arrest. Cardiovasc Res 2010; 87 (03) 552-560
• 22 Chambers DJ, Fallouh HB. Cardioplegia and cardiac surgery: pharmacological arrest and cardioprotection during global ischemia and reperfusion. Pharmacol Ther 2010; 127 (01) 41-52
• 23 Scorsin M, Mebazaa A, Al Attar N. et al. Efficacy of esmolol as a myocardial protective agent during continuous retrograde blood cardioplegia. J Thorac Cardiovasc Surg 2003; 125 (05) 1022-1029
• 24 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
• 25 Aass T, Stangeland L, Moen CA. et al. Myocardial function after polarizing versus depolarizing cardiac arrest with blood cardioplegia. J Thorac Cardiovasc Surg 2003; 125: 1022-1029
• 26 Fujii M, Chambers DJ. Cardioprotection with esmolol cardioplegia: efficacy as a blood-based solution. Eur J Cardiothorac Surg 2013; 43 (03) 619-627
• 27 Aass T, Chambers DJ, Haaverstad R, Grong K. Reply to Choi and Stamm. Eur J Cardiothorac Surg 2017; 51 (03) 608-609