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Off-pump myocardial revascularization attenuates endothelin-1 expression in systemic, pulmonary, and coronary circulation

Koronararterien-Bypass ohne extrakorporale Zirkulation abmildert Endothelin-1-Ausdruck in systemische, pulmonale und koronare Zirkulation

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Summary

Objective

The objective of this study was to evaluate the influence of cardiopulmonary bypass (CPB) on endothelin-1 (ET-1) expression in various circulation compartments in patients undergoing myocardial revascularization.

Methods

A total of 30 patients were randomized to undergo myocardial revascularization with (CABG, n = 15) or without (OPCAB, n = 15) CPB. Samples were taken preoperatively, after establishing CPB and after CPB (CABG group), prior to and after revascularization (OPCAB group), and 6 and 24 h postoperatively. Values of ET-1 were compared between groups at all time points and correlated with postoperative cardioselective enzyme values and clinical parameters.

Results

In OPCAB group, ET-1 levels did not significantly vary between time points. In CABG group, ET-1 levels were significantly elevated vs. baseline in arterial: ART-T2 vs. ART-T0 (1.83 ± 1.81 vs. 0.76 ± 1.07 fmol/mL, p = 0.05), pulmonary: SG-T2 vs. SG-T0 (2.70 ± 2.75 vs. 0.39 ± 0.28 fmol/mL, p < 0.001) and SG-T3 vs. SG-T0 (1.56 ± 0.28 vs. 0.39 ± 0.28 fmol/mL, p < 0.001), and coronary circulation CS-T2 vs. CS-T1 (1.12 ± 0.49 vs. 0.27 ± 0.09 fmol/mL, p = 0.01). ET-1 levels were significantly higher in CABG group in all vascular compartments: ART-T2 (1.83 ± 1.81 vs. 0.17 ± 0.16 fmol/mL, p = 0.02), ART-T4 (0.99 ± 0.56 vs. 0.24 ± 0.12 fmol/mL, p = 0.01), SG-T1 (0.59 ± 0.15 vs. 0.25 ± 0.13 fmol/mL, p = 0.01), SG-T2 (2.70 ± 2.75 vs. 0.30 ± 0.24 fmol/mL, p = 0.004), SG-T3 (1.56 ± 0.28 vs. 0.35 ± 0.31 fmol/mL, p < 0.001), SG-T4 (1.34 ± 0.11 vs. 0.34 ± 0.16 fmol/mL, p < 0.001), and CS-T2 (1.12 ± 0.49 vs. 0.12 ± 0.12 fmol/mL, p = 0.004). Coronary sinus ET-1 level after CPB (CS-T2) in CABG group correlated positively with troponin-I level 24 h postoperatively (r 2 = 0.802, p = 0.02)

Conclusion

Off-pump myocardial revascularization attenuates ET-1 expression in all investigated vascular compartments. Elevated coronary ET-1 levels after CPB in CABG group correlate with troponin-I levels 24 h postoperatively.

Zusammenfassung

Ziel

war es, den Einfluss eines kardiopulmonalen Bypasses auf die Endothelin-1 (ET-1) Expression in verschiedenen Kreislauf Kompartments von Patienten mit myokardialer Revaskularisation zu erheben.

Methoden

Bei dreißig Patienten wurden eine myokardiale Revaskularisation randomisiert mit (CABG n = 15) oder ohne (OP-CAB, n = 15) Herzkreislauf Maschine (HKM) durchgeführt. Proben wurden präoperativ, nach Anschluss an die Maschine und nach dem Ende des Herzkreislauf Bypasses (CABG Gruppe), vor und nach Revaskularisation (OP-CAB Gruppe) sowie 6 und 24 h postoperativ abgenommen. Die bei beiden Gruppen erhobenen ET-1 Werte aller Blutabnahme-Zeitpunkte wurden verglichen und mit postoperativen kardioselektiven Enzymwerten sowie klinischen Parametern korreliert.

Ergebnisse

In der OP-CAB Gruppe ergab sich im gesamten Verlauf kein statistisch signifikanter Unterschied der ET-1 Konzentrationen. In der CABG Gruppe waren die ET-1 Werte signifikant im Vergleich zu den Ausgangswerte erhöht: arteriell – ART-T2 vs. ART-T0 (1,83 ± 1,81 vs. 0,76 ± 1,07 fmol/mL, p = 0,05), pulmonal arteriell – SG-T2 vs. SG-T0 (2,70 ± 2,75 vs. 0,39 ± 0,28 fmol/mL, p < 0,001), SG-T3 vs. SG-T0 (1,56 ± 0,28 vs. 0,39 ± 0,28 fmol/mL, p < 0,001) und Koronar Kreislauf CST2 vs. CS-T1 (1,12 ± 0,49 vs. 0,27 ± 0,09 fmol/mL, p = 0,01). Die ET-1 Konzentrationen waren in der CABG –Gruppe in allen Gefäß-Kompartments signifikant höher: ART-T2 (1,83 ± 1,81 vs. 0,17 ± 0,16 fmol/mL, p = 0,02); ARTT4 (0,99 ± 0,56 vs. 0,24 ± 0,12 fmol/mL, p = 0,01); SG-T1 (0,59 ± 0,15 vs. 0,25 ± 0,13 fmol/mL, p = 0,01); SG-T2 (2,70 ± 2,75 vs. 0,30 ± 0,24 fmol/mL, p = 0,004); SG-T3 (1,56 ± 0,28 vs. 0,35 ± 0,31 fmol/mL, p < 0,001); SG-T4 (1,34 ± 0,11 vs. 0,34 ± 0,16 fmol/mL, p < 0,001); CS-T2 (1,12 ± 0,49 vs. 0,12 ± 0,12 fmol/mL, p = 0,004).

Die ET-1 Konzentrationen im Koronarsinus waren nach dem Herz-Kreislauf Bypass in der CABG Gruppe positiv mit den 24 Stunden- postoperativen Troponin-I Werten korreliert (r 2 = 0,802, p = 0,02).

Schlussfolgerung

Eine myokardiale Revaskularisation off-pump schwächt die ET-1 Expression in allen untersuchten Gefäßgebieten ab. Die nach der Herz Lungen Maschine erhöhten ET-1 Werte der CABG Gruppe korrelieren mit den 24 h postoperativ gemessenen Troponin-I Werten.

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References

  1. Yanagisawa M, Kurihara H, Kimura S, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988;332(6163):411–5.

    Article  CAS  PubMed  Google Scholar 

  2. Ergul A. Endothelin-1 and endothelin receptor antagonists as potential cardiovascular therapeutic agents. Pharmacotherapy. 2002;22(1):54–65.

    Article  CAS  PubMed  Google Scholar 

  3. Vallely MP, Bannon PG, Hughes CF, Kritharides L. Endothelial cell adhesion molecules and cardiopulmonary bypass. Asian Cardiovasc Thorac Ann. 2001;9(4):349–55.

    Article  Google Scholar 

  4. Cohn LH. Chapter 12: Extracorporeal circulation. In: Cardiac surgery in the adult. 3rd ed. New York: McGraw-Hill; 2008. p. 370–89.

  5. Onorati F, Rubino AS, Nucera S, et al. Off-pump coronary artery bypass surgery versus standard linear or pulsatile cardiopulmonary bypass: endothelial activation and inflammatory response. Eur J Cardiothorac Surg. 2010;37(4):897–904.

    Article  PubMed  Google Scholar 

  6. Matsuura A, Yamochi W, Hirata K, Kawashima S, Yokoyama M. Stimulatory interaction between vascular endothelial growth factor and endothelin-1 on each gene expression. Hypertension. 1998;32(1):89–95.

    Article  CAS  PubMed  Google Scholar 

  7. Agui T, Xin X, Cai Y, Sakai T, Matsumoto K. Stimulation of interleukin-6 production by endothelin in rat bone marrow-derived stromal cells. Blood. 1994;84(8):2531–8.

    CAS  PubMed  Google Scholar 

  8. Hofman FM, Chen P, Jeyaseelan R. Endothelin-1 induces production of the neutrophil chemotactic factor interleukin-8 by human brain-derived endothelial cells. Blood. 1998;92(9):3064–72.

    CAS  PubMed  Google Scholar 

  9. Danˇová K, Pechánˇ I, Olejárová I, Líška B. Natriuretic peptides and endothelin-1 in patients undergoing coronary artery bypass grafting. Gen Physiol Biophys. 2007;26(3):194–9.

    PubMed  Google Scholar 

  10. Dorman BH, Bond BR, Clair MJ, et al. Temporal synthesis and release of endothelin within the systemic and myocardial circulation during and after cardiopulmonary bypass: relation to postoperative recovery. J Cardiothorac Vasc Anesth. 2000;14(5):540–5.

    Article  CAS  PubMed  Google Scholar 

  11. Mathieu P, Dupuis J, Carrier M, et al. Pulmonary metabolism of endothelin-1 during on-pump and beating heart coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2001;121(6):1137–42.

    Article  CAS  PubMed  Google Scholar 

  12. Multani MM, Ikonomidis JS, Kim PY, et al. Dynamic and differential changes in myocardial and plasma endothelin in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2005;129(3):584–90.

    Article  CAS  PubMed  Google Scholar 

  13. Taylor KM, Bain WH, Jones JV, Walker MS. The effect of hemodilution of plasma levels of cortisol and free cortisol. J Thorac Cardiovasc Surg. 1976;72(1):57–61.

    CAS  PubMed  Google Scholar 

  14. Yokokawa K, Tahara H, Kohno M, Mandal AK, Yanagisawa M, Takeda T. Heparin regulates endothelin production through endothelium-derived nitric oxide in human endothelial cells. J Clin Invest. 1993;92(4):2080–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Lundblad R, Moen O, Fosse E. Endothelin-1 and neutrophil activation during heparin-coated cardiopulmonary bypass. Ann Thorac Surg. 1997;63(5):1361–7.

    Article  CAS  PubMed  Google Scholar 

  16. Hernández-Perera O, Pérez-Sala D, Navarro-Antolín J, et al. Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin Invest. 1998;101(12):2711–9.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Dupuis J, Stewart DJ, Cernacek P, Gosselin G. Human pulmonary circulation is an important site for both clearance and production of ET-1. Circulation. 1996;94(7):1578–84.

    Article  CAS  PubMed  Google Scholar 

  18. Parker JD, Thiessen JJ, Reilly R, Thong JH, Stewart DJ, Shekar Pandey A. Human Endothelin-1 clearance revealed by a radiotracer technique. J Pharmacol Exp Ther. 1999;289(1):261–5.

    CAS  PubMed  Google Scholar 

  19. Dorman BH, Kratz J, Multani MM, et al. A prospective randomized study of endothelin and postoperative recovery in off-pump versus conventional coronary artery bypass surgery. J Cardiothorac Vasc Anesth. 2004;18(1):25–9.

    Article  CAS  PubMed  Google Scholar 

  20. Walker CA, Baicu SC, Goldberg AT, et al. Temporal endothelin dynamics of the myocardial interstitium and systemic circulation in cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2000;120(5):864–71.

    Article  CAS  PubMed  Google Scholar 

  21. Franco-Cereceda F, Barr G, Owall A, Liska J, Lundberg JM. Is Endothelin-1 release at reperfusion of the ischaemic human heart due to cold-induced displacement of endothelin from binding sites? Eur J Pharmacol. 1995;279(1):105–7.

    Article  CAS  PubMed  Google Scholar 

  22. Kinlay S, Behrendt D, Wainstein M, et al. Role of endothelin-1 an the active constriction of human atherosclerotic coronary arteries. Circulation. 2001;104(10):1114–8.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiac and Transplant Surgery, Dubrava University Hospital, Av. G. Šuška 6, HR-10 000, Zagreb, Croatia

    Daniel Unić MD, Davor Barić MD, Kristina Brkić PhD, Mislav Planinc MD, Dubravka Jonjić MD, Igor Rudež MD, PhD & Željko Sutlić MD, PhD

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  1. Daniel Unić MD
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Unić, D., Barić, D., Brkić, K. et al. Off-pump myocardial revascularization attenuates endothelin-1 expression in systemic, pulmonary, and coronary circulation. Wien Klin Wochenschr 126, 710–717 (2014). https://doi.org/10.1007/s00508-014-0664-8

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