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Antioxidants for the Treatment of Endothelial Dysfunction in Critical Illness

  • Conference paper
Intensive Care Medicine

Part of the book series: Yearbook of Intensive Care and Emergency Medicine ((YEARBOOK,volume 2007))

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Abstract

Before 1980, the endothelium was considered to be an inert hemostatic barrier. Furchgott and Zawadzki were the first to demonstrate the necessity of the vascular endothelium for vasodilatation to acetylcholine [1]. If the vascular endothelium was removed, the blood vessel failed to relax in response to acetylcholine, but still responded to glyceryl trinitrate. This endothelium-dependent vasodilatation is mediated by an endogenous mediator, initially named endothelium-derived relaxing factor (EDRF), but which was subsequently identified as nitric oxide (NO). From this discovery a new era of endothelial research developed. The endothelium is now known to have a key role in themaintenance of vascular homeostasis. It actively regulates vascular tone, platelet aggregation, coagulation, fibrinolysis, and leukocyte activation [2]. Endothelial function is impaired in critical illness and may be important in the pathophysiology of multiple organ failure (MOF) [3].

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References

  1. Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376

    Article  CAS  PubMed  Google Scholar 

  2. De Caterina R (2000) Endothelial dysfunctions: common denominators in vascular disease. Curr Opin Clin Nutr Metab Care 3:453–467

    Article  PubMed  Google Scholar 

  3. Cardigan R, McGloin H, Mackie I, Machin S, Singer M (1998) Endothelial dysfunction in critically ill patients: the effect of haemofiltration. Intensive Care Med 24(12):1264–1271

    Article  CAS  PubMed  Google Scholar 

  4. Landmesser U, Harrison DG (2001) Oxidant stress as a marker for cardiovascular events: Ox marks the spot. Circulation 104:2638–2640

    CAS  PubMed  Google Scholar 

  5. Oldham KM, Bowen PE (1998) Oxidative stress in critical care: is antioxidant supplementation beneficial? J Am Diet Assoc 98:1001–1008

    Article  CAS  PubMed  Google Scholar 

  6. Therond P, Bonnefont-Rousselot D, Davit-Spraul A, Conti M, Legrand A (2000) Biomarkers of oxidative stress: an analytical approach. Curr Opin Clin Nutr Metab Care 3:373–384

    Article  CAS  PubMed  Google Scholar 

  7. Carr A, Frei B (2000) The role of natural antioxidants in preserving the biological activity of endothelium-derived nitric oxide. Free Radic Biol Med 28(12):1806–1814

    Article  CAS  PubMed  Google Scholar 

  8. Heyland DK, Dhaliwal R, Suchner U, Berger MM (2005) Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill. Intensive Care Med 31:327–337

    Article  PubMed  Google Scholar 

  9. Cooke JP (2000) The endothelium: a new target for therapy. Vasc Med 5:49–453

    CAS  PubMed  Google Scholar 

  10. Moncada S, Higgs A (1993) The L-arginine-nitric oxide pathway. N Engl J Med 329:2002–2012

    Article  CAS  PubMed  Google Scholar 

  11. Hürlimann D, Ruschitzka F, Lüscher TF (2002) The relationship between the endothelium and the vessel wall. Eur Heart 4(Suppl A): A1–7

    Google Scholar 

  12. Hingorani AD, Cross J, Kharbanda RK, et al (2000) Acute systemic inflammation impairs endothelium-dependent dilatation in humans. Circulation 102:994–999

    CAS  PubMed  Google Scholar 

  13. Williams SB, Goldfine AB, Timimi FK, et al (1998) Acute hyperglycaemia attenuates endothelium-dependent vasodilation in humans in vivo. Circulation 97:1695–1701

    CAS  PubMed  Google Scholar 

  14. Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron AD (1996) Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest 97:2601–2610

    Article  CAS  PubMed  Google Scholar 

  15. Chowienczyk PJ, Watts GF, Cockcroft JR, Ritter JM (1992) Impaired endothelium-dependent vasodilatation of forearm resistance vessels in hypercholesterolaemia. Lancet 340:1430–1432

    Article  CAS  PubMed  Google Scholar 

  16. Bae JH, Bassenge E, Kim KB, et al (2001) Postprandial hypertriglyceridemia impairs endothelial function by enhanced oxidant stress. Atherosclerosis 155:517–423

    Article  CAS  PubMed  Google Scholar 

  17. Steinberg HO, Tarshoby M, Monestel R, et al (1997) Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. J Clin Invest 100:1230–1239

    Article  CAS  PubMed  Google Scholar 

  18. Kuhn FE, Mohler ER, Satler LF, Reagan K, Lu DY, Rackley CE (1991) Effects of high density lipoprotein on acetylcholine-induced coronary vasoreactivity. Am J Cardiol 68:1425–1430

    Article  CAS  PubMed  Google Scholar 

  19. Vakkilainen J, Makimattila S, Seppala-Lindroos A, et al (2000) Endothelial dysfunction in men with small LDL particles. Circulation 102:716–721

    CAS  PubMed  Google Scholar 

  20. Tawakol A, Forgione MA, Stuehlinger M, et al (2002) Homocysteine impairs coronary microvascular dilator function in humans. J Am Coll Cardiol 40:1051–1058

    Article  CAS  PubMed  Google Scholar 

  21. Cooke JP (2000) Does ADMA cause endothelial dysfunction? Arterioscler, Thromb Vasc Biol 20:2032–2037

    CAS  Google Scholar 

  22. Van Den Berghe G, Wouthers P, Weekers F, et al (2001) Intensive insulin therapy in critically ill patients. N Engl J Med 345:1359–1367

    Article  PubMed  Google Scholar 

  23. Khovidhunkit W, Kim M-S, Memon RA, et al (2004) Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J Lipid Res 45:1169–1196

    Article  CAS  PubMed  Google Scholar 

  24. Nijveldt RJ, Teerlink T, Van Leeuwen PAM (2003) The asymmetrical dimethylarginine (ADMA) — multiple organ failure hypothesis. Clin Nutr 22:99–104

    Article  CAS  PubMed  Google Scholar 

  25. Yang Z, Ming X-F (2006) Recent advances in understanding endothelial dysfunction in atherosclerosis. Clin Med Res 1:53–65

    Article  Google Scholar 

  26. Griendling KK, Minieri CA, Ollerenshaw JD, Alexander RW (1994) Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res 74:1141–1148

    CAS  PubMed  Google Scholar 

  27. Stroes ESG, van Faassen EE, van Londen GJ, Rabelink TJ (1998) Oxygen radical stress in vascular disease: the role of endothelial nitric oxide synthase. J Cardiovasc Pharmacol 32(suppl 3): S14–21

    CAS  PubMed  Google Scholar 

  28. West IC (2000) Radicals and oxidative stress in diabetes. Diabetic Med 17: 171–180

    Article  CAS  PubMed  Google Scholar 

  29. Gutterman DD (2002) Vascular dysfunction in hyperglycemia: is protein kinase C the culprit? Circ Res 90:5–7

    Article  CAS  PubMed  Google Scholar 

  30. Gryglewski RJ, Palmer RMJ, Moncada S (1986) Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 320:454–456

    Article  CAS  PubMed  Google Scholar 

  31. Lynch S, Frei B (1993) Mechanisms of copper-and iron-dependent oxidative modification of human low density lipoprotein. J Lipid Res 34:1745–1753

    CAS  PubMed  Google Scholar 

  32. Hein TW, Liao JC, Kuo L (2000) oxLDL specifically impairs endothelium-dependent, NO-mediated dilation of coronary arterioles. Am J Physiol Heart Circ Physiol 278:H175–183

    CAS  PubMed  Google Scholar 

  33. Patel JM, Block ER (1995) Sulfhydryl-disulfide modulation and the role of disulfide oxidoreductases in regulation of the catalytic activity of nitric oxide synthase in pulmonary artery endothelial cells. Am J Respir Cell Mol Biol 13:352–359

    CAS  PubMed  Google Scholar 

  34. Murphy ME (1999) Ascorbate and dehydroascorbate modulate nitric oxide-induced vasodilations of rat coronary arteries. J Cardiovasc Pharmacol 34:295–303

    Article  CAS  PubMed  Google Scholar 

  35. Altavilla D, Saitta A, Guarini S, et al (2001) Oxidative stress causes nuclear factor-kappa q activation in acute hypovolemic hemorrhagic shock. Free Radic Biol Med 30:1055–1066

    Article  CAS  PubMed  Google Scholar 

  36. Abello PA, Fidler SA, Buckley GB, Buchman TG (1994) Antioxidants modulate induction of programmed endothelial cell death (apoptosis) by endotoxin. Arch Surg 129:134–140

    CAS  PubMed  Google Scholar 

  37. Maxwell SRJ (1995) Prospects for the use of antioxidant therapies. Drugs 49:345–361

    Article  CAS  PubMed  Google Scholar 

  38. Halcox JPJ, Schenke WH, Zalos G, et al (2002) Prognostic value of coronary vascular endothelial dysfunction. Circulation 106:653–658

    Article  PubMed  Google Scholar 

  39. Gokce N, Keaney JF, Hunter LM, Watkins MT, Menzoian JO, Vita JA (2002) Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function. A prospective study. Circulation 105:1567–1572

    Article  PubMed  Google Scholar 

  40. Gosling P, Brudney S, McGrath L, Riseboro S, Manji M (2003) Mortality prediction at admission to intensive care: a comparison of microalbuminuria with acute physiology scores after 24 hours. Crit Care Med 31:98–103

    Article  CAS  PubMed  Google Scholar 

  41. Vallance P, Chan N (2001) Endothelial function and nitric oxide: clinical relevance. Heart 85:342–350

    Article  CAS  PubMed  Google Scholar 

  42. Mullan BA, Fee HJ, Young IS, McCance DR (2004) Protective effects of ascorbic acid on arterial hemodynamics during acute hyperglycemia. Am J Physiol Heart Circ Physiol 287:H1262–268

    Article  CAS  PubMed  Google Scholar 

  43. Mullan BA, Ennis CN, Fee HJP, Young IS, McCance DR (2005) Pretreatment with intravenous ascorbic acid preserves endothelial function during acute hyperglycaemia. Clin Exp Pharmacol Physiol 32:340–345

    Article  CAS  PubMed  Google Scholar 

  44. Van den Berghe G, Wouters PJ, Bouillon R, et al (2003) Outcome benefit of intensive insulin therapy in the critically ill: insulin dose versus glycaemic control. Crit Care Med 31:359–366

    Article  PubMed  Google Scholar 

  45. Tyml K, Li F, Wilson JX (2005) Delayed ascorbate bolus protects against maldistribution of microvascular blood flow in septic rat skeletal muscle. Crit Care Med 33:1823–1828

    Article  CAS  PubMed  Google Scholar 

  46. Pleiner J, Mittermayer F, Schaller G, MacAllister RJ, Wolzt M (2002) High doses of vitamin C reverse Escherichia coli endotoxin-induced hyporeactivity to acetylcholine in the human forearm. Circulation 106:1460–1464

    Article  CAS  PubMed  Google Scholar 

  47. Schmidt H, Schmidt W, Muller T, Bohrer H, Gebhard MM, Martin E (1997) N-acetylcysteine attenuates endotoxin-induced leukocyte-endothelial cell adhesion and macromolecular leakage in vivo. Crit Care Med 25:858–863

    Article  CAS  PubMed  Google Scholar 

  48. Tanaka H, Matsuda T, Miyagantani Y, Yukioka T, Matsuda H, Shimazaki S (2000) Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration. Arch Surg 135:326–331

    Article  CAS  PubMed  Google Scholar 

  49. Nathens AB, Neff MJ, Jurkovich GJ, et al (2002) Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients. Ann Surg 236:814–822

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Regional Intensive Care Unit, Royal Group of Hospitals, Grosvenor Road, Belfast, BT12 6BA, UK

    B. Mullan, M. Duffy & D. McAuley

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  2. M. Duffy
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  3. D. McAuley
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© 2007 Springer Science + Business Media Inc.

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Mullan, B., Duffy, M., McAuley, D. (2007). Antioxidants for the Treatment of Endothelial Dysfunction in Critical Illness. In: Intensive Care Medicine. Yearbook of Intensive Care and Emergency Medicine, vol 2007. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-49433-1_10

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  • DOI: https://doi.org/10.1007/978-3-540-49433-1_10

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-49432-4

  • Online ISBN: 978-3-540-49433-1

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