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Preoperative unstable angina causes venous adaptation to surgical graft injury

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Abstract

Ischemic preconditioning may provide a systemic organ protection, evident as the phenomenon known as remote preconditioning. Unstable angina may be a clinical analogue to ischemic preconditioning. Vein graft harvesting induces inflammation of the graft wall. We hypothesized that preoperative unstable angina preconditions vein grafts and reduces the inflammatory response to graft harvesting.

Consecutive patients with stable or unstable angina undergoing open heart surgery (n = 12 in each group) were studied. Saphenous vein biopsies were collected at the start of graft harvesting, and when the last proximal anastomosis to the aorta was finished (average 112 minutes later). Gene expression of inflammatory mediators (tumor necrosis factor alpha, interleukin-1β (IL-1β), E-selectin (CD62E), intercellular leukocyte adhesion molecule 1, inducible nitric oxide synthase, endothelin-1) increased after surgical handling (semiquantitative RT-PCR). In vein grafts from unstable patients the increase was attenuated for Il-1β (p < 0.004) and CD62E (p < 0.001). In stable patients the protein expression of IκBα and heat shock protein72 was reduced by surgical handling (p < 0.04), but was not influenced in unstable patients (immunoblotting). In vitro relaxation to acetylcholine was enhanced, and contractions to phenylephrine and endothelin-1 were attenuated in veins rings from unstable patients (p < 0.003).

In conclusion, surgical handling of vein grafts induces inflammation of the vessel wall. This response was reduced in grafts from patients with unstable angina, indicating a possible systemic preconditioning-like effect of acute coronary syndromes.

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References

  1. Bolli R (2001) Cardioprotective function of inducible nitric oxide synthase and role of nitric oxide in myocardial ischemia and reperfusion: an overview of a decade of research. J Mol Cell Cardiol 33:1897–918

    Article  CAS  PubMed  Google Scholar 

  2. Bonatti J, Oberhuber A, Schachner T, Zou Y, Hammerer-Lercher A, Mittermair PG (2004) Neointimal hyperplasia in coronary vein grafts: pathophysiology and prevention of a significant clinical problem. Heart Surg Forum 7:72–87

    PubMed  Google Scholar 

  3. Carter DA (1997) Modulation of cellular AP-1 DNA binding activity by heat shock proteins. FEBS Lett 416:81–85

    Article  CAS  PubMed  Google Scholar 

  4. Crook MF, Newby AC, Southgate KM (2000) Expression of intercellular adhesion molecules in human saphenous veins: effects of inflammatory cytokines and neointima formation in culture. Atherosclerosis 150:33–41

    Article  CAS  PubMed  Google Scholar 

  5. DeFily DV, Chilian WM (1993) Preconditioning protects coronary arteriolar endothelium from ischemia-reperfusion injury. Am J Phys 265:H700–H706

    CAS  Google Scholar 

  6. Galea J, Armstrong J, Francis SE, Cooper G, Crossman DC, Holt CM (1999) Alterations in c-fos expression, cell proliferation and apoptosis in pressure distended human saphenous vein. Cardiovasc Res 44:436–448

    Article  CAS  PubMed  Google Scholar 

  7. Gutsman-Conrad A, Heydari AR, You S, Richardson A (1998) The expression of heat shock protein 70 decreases with cellular senescence in vitro and in cells derived from young and old human subjects. Exp Cell Res 241:404–413

    Article  Google Scholar 

  8. Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352:1685–1695

    Article  CAS  PubMed  Google Scholar 

  9. Hiasa G, Hamada M, Ikeda S, Hiwada K (2001) Ischemic preconditioning and lipopolysaccharide attenuate nuclear factor kappa-B activation and gene expression of inflammatory cytokines in the ischemic-reperfused rat heart. Jpn Circ J 65:984–990

    Article  CAS  PubMed  Google Scholar 

  10. Hinokiyama K, Valen G, Tokuno S, Vedin J, Vaage J (2006) Vein graft harvesting induces inflammation and impairs vessel reactivity. Ann Thor Surg 82:1458–1464

    Article  Google Scholar 

  11. Hirai T, Fujita M, Yamanishi K, Ohno A, Miwa K, Sasayama S (1993) Significance of preinfarction angina for preservation of left ventricular function in acute myocardial infarction. Am Heart J 124:19–23

    Article  Google Scholar 

  12. Iyer VS, Russell WJ, Leppard P, Craddock D (1993) Mortality and myocardial infarction after coronary artery surgery. Med J Australia 159:166–170

    CAS  PubMed  Google Scholar 

  13. Kloner RA, Shook T, Przyklenk K, Davis VG, Junio L, Matthews RV, Burstein S, Gibson M, Poole K, Cannon CP, McCabe CH, Braunwald E (1995) Previous angina alters in-hospital outcome in TIMI 4.A clinical correlate to preconditioning? Circulation 91:37–47

    CAS  PubMed  Google Scholar 

  14. Laude K, Thuillez C, Richard V (2001) Coronary endothelial dysfunction after ischemia and reperfusion: A new therapeutic target? Brazilian J Med Biol Res 34:1–7

    CAS  Google Scholar 

  15. Lim R, Laskey WK (1997) Ischemic preconditioning in unstable coronary syndromes: evidence dependence. J Am Coll Cardiol 30:1461–1465

    Article  CAS  PubMed  Google Scholar 

  16. Marber MS, Latchman DS, Walker JM, Yellon DM (1993) Cardiac stress protein elevation 24 hours after brief ischaemia or heat stress is associated with resistance to myocardial infarction. Circulation 88:1264–1272

    CAS  PubMed  Google Scholar 

  17. De Martin R, Hoeth M, Hofer-Warbinek R, Schmid JA (2000) The transcription factor NF-kappa B and the regulation of vascular cell function. Arterioscler Thromb Vasc Biol 20:83–88

    Google Scholar 

  18. Mehta JL, Saldeen TGP, Rand K (1998) Interactive role of infection, inflammation and traditional risk factors in atherosclerosis and coronary artery disease. J Am Coll Cardiol 31:1217–1225

    Article  CAS  PubMed  Google Scholar 

  19. Newby AC, Zaltsman AB (2000) Molecular mechanisms in intimal hyperplasia. J Pathol 190:300–309

    Article  CAS  PubMed  Google Scholar 

  20. Pratt PF, Wang C, Weirauch D, Bienengraeber MW, Kersten JR, Pagel PS, Warltier DC (2006) Cardioprotection by volatile anesthetics: new applications for old drugs? Curr Opin Anaesthesiol 19:397–403

    Article  PubMed  Google Scholar 

  21. Przyklenk K, Darling CE, Dickson EW, Whittaker P (2003) Cardioprotection "outside the box". Basic Res Cardiol 98:149–157

    PubMed  Google Scholar 

  22. Psychari SN, Ilidromitits EK, Hamodraka E, Liakos G, Velissaridou A, Apostolous A, Kremastinos DT (2004) Preinfarction angina does not alter infarct size and in hospital outcome after acute myocardial infarction with ST elevation. Int J Cardiol 94:187–191

    Article  PubMed  Google Scholar 

  23. Ritchie ME (1998) Nuclear factor-κB is selectively and markedly activated in humans with unstable angina pectoris. Circulation 98:1707–1713

    CAS  PubMed  Google Scholar 

  24. Schulz R, Cohen MV, Behrends M, Downey JM, Heusch G (2001) Signal transduction of ischemic preconditioning. Cardiovasc Res 52:181–198

    Article  CAS  PubMed  Google Scholar 

  25. Squadrito F, Deodato B, Bova A,Marini H, Saporito F, Calo M, Giacca M, Minutoli L,Venuti FS, Caputi AP, Altavilla D (2003) Crucial role of nuclear factor-κB in neointimal hyperplasia of the mouse carotid artery after interruption of blood flow. Atherosclerosis 166:233–242

    Article  CAS  PubMed  Google Scholar 

  26. Tokuno S, Hinokiyama K, Tokuno K, Löwbeer C, Valen G (2002) Spontaneous ischemic events in the heart and brain preconditions the hearts of severely atherosclerotic mice. Atherosclerosis, Thrombosis and Vascular Biology 22:995–1001

    Article  CAS  Google Scholar 

  27. Tokuno S, Chen F, Jiang J, Pernow J, Valen G (2002) Effects of spontaneous or induced brain infarctions on vessel reactivity: The role of iNOS. Life Sciences 71:679–692

    Article  CAS  PubMed  Google Scholar 

  28. Tomoda H, Aoki N (2004) Coronary blood flow in evolving myocardial infarction preceded by preinfarction angina: a critical reevaluation of preconditioning effect in clinical cases. Angiology 55:9–15

    Article  PubMed  Google Scholar 

  29. Tähepôld P, Elfström P, Eha I, Kals J, Taal G, Taalonpoika A, Valen G, Vaage J, Starkopf J (2002) Exposure of rats to hyperoxia enhances the relaxation of isolated aortic rings and reduces the infarct size of isolated hearts. Acta Physiol Scand 175:271–277

    Article  PubMed  Google Scholar 

  30. Tähepôld P, Starkopf J, Vaage J, Valen G (2003) Hyperoxia elicits preconditioning through a NFκB-dependent mechanism in the rat heart. J Thorac Cardiovasc Surg 125:650–660

    Article  PubMed  Google Scholar 

  31. Valen G (2003) Cellular signalling mechanisms in adaptation to ischemiainduced myocardial damage. Ann Med 35:1–8

    Article  Google Scholar 

  32. Valen G, Hansson GK, Dumitrescu A, Vaage J (2000) Unstable angina activates myocardial heat shock protein 72, endothelial nitric oxide synthase, and transcription factors NFκB and AP-1. Cardiovasc Res 47:49–56

    Article  CAS  PubMed  Google Scholar 

  33. Valen G, Paulsson G, Bennet A, Hansson GK, Vaage J (2000) Gene expression of inflammatory mediators in different chambers of the human heart. Ann Thorac Surg 70:562–567

    Article  CAS  PubMed  Google Scholar 

  34. Vayssier M, Favatier F, Pinot F, Bachelet M, Polla BS (1998) Tobacco smoke induces coordinate activation of HSF and inhibition of NFkappaB in human monocytes: effects on TNFalpha release. Biochem Biophys Res Commun 252:249–256

    Article  CAS  PubMed  Google Scholar 

  35. Vural KM, Oz MC, Liao H, Batirel HF, Pinsky DJ (1999) Membrane stabilization in harvested vein graft storage: effects on adhesion molecule expression and nitric oxide synthesis. Eur J Cardio-Thorac Surg 16:150–155

    Article  CAS  Google Scholar 

  36. Wu ZQ, Pehkonen E, Laurikka J, Kaukinen L, Honkonen EL, Kaukinen S, Tarkka M (2000) Protective effects of unstable angina in coronary artery bypass surgery. Scand Cardiovasc J 34: 486–492

    Article  CAS  PubMed  Google Scholar 

  37. Xuan Y-T, Tang X-L, Banerjee S, Takano H, Li R CX, Han H, Bolli R (1999) Nuclear factor-κB plays an essential role in the late phase of ischemic preconditioning in conscious rabbits. Circ Res 84:1095–1109

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Basic Medical Science, Dept. of Physiology University of Oslo, 1103 Blindern, 0317, Oslo, Norway

    G. Valen

  2. Crafoord Laboratory of Experimental Surgery, Karolinska Hospital, Stockholm, Sweden

    K. Hinokiyama

  3. Dept. of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden

    J. Vedin

  4. Dept. of Surgery, Faculty Division Ulleval University Hospital University of Oslo, Oslo, Norway

    J. Vaage

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  1. G. Valen
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  2. K. Hinokiyama
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  3. J. Vedin
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  4. J. Vaage
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Correspondence to G. Valen.

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Valen, G., Hinokiyama, K., Vedin, J. et al. Preoperative unstable angina causes venous adaptation to surgical graft injury. Basic Res Cardiol 102, 265–273 (2007). https://doi.org/10.1007/s00395-007-0642-7

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  • DOI: https://doi.org/10.1007/s00395-007-0642-7

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