Skip to main content
SpringerLink
Log in

Metabolic derangement and cardiac injury early after reperfusion following intermittent cross-clamp fibrillation in patients undergoing coronary artery bypass graft surgery using conventional or miniaturized cardiopulmonary bypass

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Myocardial ischemic stress and early reperfusion injury in patients undergoing coronary artery bypass grafting (CABG) operated on using intermittent cross-clamp fibrillation (ICCF) are not presently known. The role of mini-cardiopulmonary bypass (mCPB) versus conventional CPB (cCPB) during ICCF has not been investigated. These issues have been addressed as secondary objective of randomised controlled trial (ISRCTN30610605) comparing cCPB and mCPB. Twenty-six patients undergoing primary elective CABG using ICCF were randomised to either cCPB or mCPB. Paired left ventricular biopsies collected from 21 patients at the beginning and at the end of CPB were used to measure intracellular substrates (ATP and related compounds). Cardiac troponin T (cTnT) and CK-MB levels were measured in plasma collected from all patients preoperatively and after 1, 30, 60, 120, and 300 min after institution of CPB. ICCF was associated with significant ischemic stress as seen by fall in energy-rich phosphates early after reperfusion. There was also a fall in nicotinamide adenine dinucleotide (NAD+) indicating cardiomyocyte death which was confirmed by early release of cTnT and CK-MB during CPB. Ischemic stress and early myocardial injury were similar for cCPB and mCPB. However, the overall cardiac injury was significantly lower in the mCPB group as measured by cTnT (mean ± SEM: 96 ± 14 vs. 59 ± 8 µg/l, p = 0.02), but not with CK-MB. ICCF is associated with significant metabolic derangement and early myocardial injury. This early outcome was not affected by the CPB technique. However, the overall cardiac injury was lower for mCPB only when measured using cTnT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

ICCF:

Intermittent cross-clamp fibrillation

CABG:

Coronary artery bypass grafting

cCPB:

Conventional cardiopulmonary bypass

mCPB:

Mini-cardiopulmonary bypass

cTnT:

Cardiac troponin T

CK-MB:

Creatine kinase

References

  1. Koster JK Jr, Cohn LH, Collins JJ Jr, Sanders JH, Muller JE, Young E (1977) Continuous hypothermic arrest versus intermittent ischemia for myocardial protection during coronary revascularization. Ann Thorac Surg 24:330–336

    Article  PubMed  Google Scholar 

  2. Karthik S, Grayson AD, Oo AY, Fabri BM (2004) A survey of current myocardial protection practices during coronary artery bypass grafting. Ann R Coll Surg Engl 86:413–415. doi:10.1308/147870804669

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Scarci M, Fallouh HB, Young CP, Chambers DJ (2009) Does intermittent cross-clamp fibrillation provide equivalent myocardial protection compared to cardioplegia in patients undergoing bypass graft revascularisation? Interact Cardiovasc Thorac Surg 9:872–878. doi:10.1510/icvts.2009.209437

    Article  PubMed  Google Scholar 

  4. Fujii M, Chambers DJ (2005) Myocardial protection with intermittent cross-clamp fibrillation: does preconditioning play a role? Eur J Cardiothorac Surg 28:821–831. doi:10.1016/j.ejcts.2005.06.048

    Article  PubMed  Google Scholar 

  5. Ascione R, Gomes WJ, Angelini GD, Bryan AJ, Suleiman MS (1998) Warm blood cardioplegia reduces the fall in the intracellular concentration of taurine in the ischaemic/reperfused heart of patients undergoing aortic valve surgery. Amino Acids 15:339–350

    Article  CAS  PubMed  Google Scholar 

  6. Pepper JR, Lockey E, Cankovic-Darracott S, Braimbridge MV (1982) Cardioplegia versus intermittent ischaemic arrest in coronary bypass surgery. Thorax 37:887–892

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Dunning J, Hunter S, Kendall SW, Wallis J, Owens WA (2006) Coronary bypass grafting using crossclamp fibrillation does not result in reliable reperfusion of the myocardium when the crossclamp is intermittently released: a prospective cohort study. J Cardiothorac Surg 1:45. doi:10.1186/1749-8090-1-45

    Article  PubMed Central  PubMed  Google Scholar 

  8. El-Essawi A, Hajek T, Skorpil J, Boning A, Sabol F, Hausmann H, Ostrovsky Y, Harringer W (2010) A prospective randomised multicentre clinical comparison of a minimised perfusion circuit versus conventional cardiopulmonary bypass. Eur J Cardiothorac Surg 38:91–97. doi:10.1016/j.ejcts.2010.01.035

    Article  PubMed  Google Scholar 

  9. Skrabal CA, Steinhoff G, Liebold A (2007) Minimizing cardiopulmonary bypass attenuates myocardial damage after cardiac surgery. ASAIO J 53:32–35. doi:10.1097/01.mat.0000249868.96923.1e

    Article  PubMed  Google Scholar 

  10. Remadi JP, Rakotoarivelo Z, Marticho P, Benamar A (2006) Prospective randomized study comparing coronary artery bypass grafting with the new mini-extracorporeal circulation Jostra system or with a standard cardiopulmonary bypass. Am Heart J 151:198. doi:10.1016/j.ahj.2005.03.067

    Article  PubMed  Google Scholar 

  11. Caputo M, Bryan AJ, Calafiore AM, Suleiman MS, Angelini GD (1998) Intermittent antegrade hyperkalaemic warm blood cardioplegia supplemented with magnesium prevents myocardial substrate derangement in patients undergoing coronary artery bypass surgery. Eur J Cardiothorac Surg 14:596–601

    Article  CAS  PubMed  Google Scholar 

  12. Momin AU, Sharabiani MT, Kidher E, Najefi A, Mulholland JW, Reeves BC, Angelini GD, Anderson JR (2013) Feasibility and safety of minimized cardiopulmonary bypass in major aortic surgery. Interact Cardiovasc Thorac Surg 17:659–663. doi:10.1093/icvts/ivt285

    Article  PubMed  Google Scholar 

  13. Imura H, Caputo M, Parry A, Pawade A, Angelini GD, Suleiman MS (2001) Age-dependent and hypoxia-related differences in myocardial protection during pediatric open heart surgery. Circulation 103:1551–1556

    Article  CAS  PubMed  Google Scholar 

  14. Ally A, Park G (1992) Rapid determination of creatine, phosphocreatine, purine bases and nucleotides (ATP, ADP, AMP, GTP, GDP) in heart biopsies by gradient ion-pair reversed-phase liquid chromatography. J Chromatogr 575:19–27

    Article  CAS  PubMed  Google Scholar 

  15. Di Lisa F, Menabo R, Canton M, Barile M, Bernardi P (2001) Opening of the mitochondrial permeability transition pore causes depletion of mitochondrial and cytosolic NAD+ and is a causative event in the death of myocytes in postischemic reperfusion of the heart. J Biol Chem 276:2571–2575

    Article  PubMed  Google Scholar 

  16. Halestrap AP, Pasdois P (2009) The role of the mitochondrial permeability transition pore in heart disease. Biochim Biophys Acta 1787:1402–1415

    Article  CAS  PubMed  Google Scholar 

  17. Ghosh S, Galinanes M (2003) Protection of the human heart with ischemic preconditioning during cardiac surgery: role of cardiopulmonary bypass. J Thorac Cardiovasc Surg 126:133–142

    Article  PubMed  Google Scholar 

  18. Lin H, Suleiman MS (2003) Cariporide enhances lactate clearance upon reperfusion but does not alter lactate accumulation during global ischaemia. Pflugers Arch 447:8–13

    Article  CAS  PubMed  Google Scholar 

  19. Korbmacher B, Simic O, Schulte HD, Sons H, Schipke JD (2004) Intermittent aortic cross-clamping for coronary artery bypass grafting: a review of a safe, fast, simple, and successful technique. J Cardiovasc Surg (Torino) 45:535–543

    CAS  Google Scholar 

  20. Cohen AS, Hadjinikolaou L, McColl A, Richmond W, Sapsford RA, Glenville BE (1997) Lipid peroxidation, antioxidant status and troponin-T following cardiopulmonary bypass. A comparison between intermittent crossclamp with fibrillation and crystalloid cardioplegia. Eur J Cardiothorac Surg 12:248–253

    Article  CAS  PubMed  Google Scholar 

  21. Musumeci F, Feccia M, MacCarthy PA, Ellis GR, Mammana L, Brinn F, Penny WJ (1998) Prospective randomized trial of single clamp technique versus intermittent ischaemic arrest: myocardial and neurological outcome. Eur J Cardiothorac Surg 13:702–709

    Article  CAS  PubMed  Google Scholar 

  22. Anderson JR, Hossein-Nia M, Kallis P, Pye M, Holt DW, Murday AJ, Treasure T (1994) Comparison of two strategies for myocardial management during coronary artery operations. Ann Thorac Surg 58:768–772 discussion 772–763

    Article  CAS  PubMed  Google Scholar 

  23. Ohata T, Mitsuno M, Yamamura M, Tanaka H, Kobayashi Y, Ryomoto M, Yoshioka Y, Tsujiya N, Miyamoto Y (2008) Beneficial effects of mini-cardiopulmonary bypass on hemostasis in coronary artery bypass grafting: analysis of inflammatory response and hemodilution. ASAIO J 54:207–209. doi:10.1097/MAT.0b013e3181648dbc

    Article  PubMed  Google Scholar 

  24. van Boven WJ, Gerritsen WB, Waanders FG, Haas FJ, Aarts LP (2004) Mini extracorporeal circuit for coronary artery bypass grafting: initial clinical and biochemical results: a comparison with conventional and off-pump coronary artery bypass grafts concerning global oxidative stress and alveolar function. Perfusion 19:239–246

    Article  PubMed  Google Scholar 

  25. Suleiman MS, Zacharowski K, Angelini GD (2008) Inflammatory response and cardioprotection during open-heart surgery: the importance of anaesthetics. Br J Pharmacol 153:21–33

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Suleiman MS, Hancock M, Shukla R, Rajakaruna C, Angelini GD (2011) Cardioplegic strategies to protect the hypertrophic heart during cardiac surgery. Perfusion 26(Suppl 1):48–56

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Hua Lin at the Bristol Heart Institute for processing blood and tissue samples and for measuring cellular metabolites. We would like to thank clinical staff members at Hammersmith Hospital, Imperial College for their valuable help and support in carrying out this study. This work was supported by the National Institute for Health Research Bristol Biomedical Research Unit in Cardiovascular Disease and the charity Heart Research UK.

Disclaimer

This article/paper/report presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Conflict of interest

None declared.

Author information

Author notes

  1. Paul C. Evans

    Present address: Department of Cardiovascular Science, University of Sheffield, Sheffield, UK

Authors and Affiliations

  1. Department of Cardiothoracic Surgery, NHLI, Hammersmith Hospital, Imperial College, London, UK

    Bao A. V. Nguyen, Jonathan R. Anderson, Paul C. Evans, Francesca Fiorentino, Barnaby C. Reeves & Gianni D. Angelini

  2. Bristol Heart Institute, University of Bristol, Bristol, UK

    M-Saadeh Suleiman

Authors
  1. Bao A. V. Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M-Saadeh Suleiman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jonathan R. Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paul C. Evans
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Francesca Fiorentino
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Barnaby C. Reeves
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gianni D. Angelini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M-Saadeh Suleiman.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nguyen, B.A.V., Suleiman, MS., Anderson, J.R. et al. Metabolic derangement and cardiac injury early after reperfusion following intermittent cross-clamp fibrillation in patients undergoing coronary artery bypass graft surgery using conventional or miniaturized cardiopulmonary bypass. Mol Cell Biochem 395, 167–175 (2014). https://doi.org/10.1007/s11010-014-2122-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-014-2122-3

Keywords

Search

Navigation