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. 1997 May;77(5):449–455. doi: 10.1136/hrt.77.5.449

Role of leucocytes in free radical production during myocardial revascularisation.

E De Vecchi 1, R Paroni 1, M G Pala 1, G Di Credico 1, V Agape 1, C Gobbi 1, P A Bonini 1, G Paolini 1, A Grossi 1
PMCID: PMC484768  PMID: 9196416

Abstract

OBJECTIVE: To evaluate the role of leucocytes in free radical production in patients with depressed or normal ejection fraction undergoing coronary bypass. DESIGN: Two randomised control trials. SETTING: Tertiary care centre. PATIENTS AND INTERVENTIONS: In the first study, 22 patients with ejection fractions of < or = 40% received blood cardioplegic reperfusion with (n = 11) or without (n = 11) leucocyte depletion. In the second study, 22 patients with ejection fractions > or = 45% received either leucocyte depleted (n = 11) or blood cardioplegia (n = 11). MAIN OUTCOME MEASURES: Glutathione, hypoxanthine, and lipid peroxidation products were measured in coronary sinus blood and plasma before aortic cross clamping and at 0, 15, and 30 minutes after unclamping. Haemodynamic variables and creatine kinase MB isoenzymes were monitored on the first postoperative day. Comparison between treatments was performed on difference (delta) between measurements at time 0 and at baseline, and on slopes obtained by fitting measurements after unclamping with a linear regression model. RESULTS: At unclamping no difference in delta for plasma glutathione redox ratio (oxidised/total glutathione, %) was observed between treated and control groups with low ejection fraction (delta = 16 (SD 8.39) and 24 (7.0) redox ratio %, respectively). Baseline value recovery rate (redox ratio %/min) was significantly faster in treated v control patients (slope -0.912 (0.380) v -0.158 (0.200), P < 0.005, respectively). Cardiac index showed a trend to greater improvement in the treated group (slope 0.04 (0.03) v 0.003 (0.002) 1/min/m2/h, P < 0.02, treated v controls, respectively). In patients with normal ejection fraction, leucocyte depletion did not result in significant improvement v controls. CONCLUSIONS: Leucocyte depletion seems to provide benefit only in patients with left ventricular dysfunction.

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Selected References

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  1. Allen B. S., Okamoto F., Buckberg G. D., Bugyi H., Young H., Leaf J., Beyersdorf F., Sjostrand F., Maloney J. V., Jr Immediate functional recovery after six hours of regional ischemia by careful control of conditions of reperfusion and composition of reperfusate. J Thorac Cardiovasc Surg. 1986 Sep;92(3 Pt 2):621–635. [PubMed] [Google Scholar]
  2. Babior B. M. The respiratory burst of phagocytes. J Clin Invest. 1984 Mar;73(3):599–601. doi: 10.1172/JCI111249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Breda M. A., Drinkwater D. C., Laks H., Bhuta S., Corno A. F., Davtyan H. G., Chang P. Prevention of reperfusion injury in the neonatal heart with leukocyte-depleted blood. J Thorac Cardiovasc Surg. 1989 May;97(5):654–665. [PubMed] [Google Scholar]
  4. Buckberg G. D. Antegrade/retrograde blood cardioplegia to ensure cardioplegic distribution: operative techniques and objectives. J Card Surg. 1989 Sep;4(3):216–238. doi: 10.1111/j.1540-8191.1989.tb00284.x. [DOI] [PubMed] [Google Scholar]
  5. Buckberg G. D. Strategies and logic of cardioplegic delivery to prevent, avoid, and reverse ischemic and reperfusion damage. J Thorac Cardiovasc Surg. 1987 Jan;93(1):127–139. [PubMed] [Google Scholar]
  6. Buckberg G. D. Update on current techniques of myocardial protection. Ann Thorac Surg. 1995 Sep;60(3):805–814. doi: 10.1016/0003-4975(95)00572-3. [DOI] [PubMed] [Google Scholar]
  7. Byrne J. G., Appleyard R. F., Lee C. C., Couper G. S., Scholl F. G., Laurence R. G., Cohn L. H. Controlled reperfusion of the regionally ischemic myocardium with leukocyte-depleted blood reduces stunning, the no-reflow phenomenon, and infarct size. J Thorac Cardiovasc Surg. 1992 Jan;103(1):66–72. [PubMed] [Google Scholar]
  8. Coghlan J. G., Flitter W. D., Clutton S. M., Ilsley C. D., Rees A., Slater T. F. Lipid peroxidation and changes in vitamin E levels during coronary artery bypass grafting. J Thorac Cardiovasc Surg. 1993 Aug;106(2):268–274. [PubMed] [Google Scholar]
  9. Curello S., Ceconi C., de Giuli F., Panzali A. F., Milanesi B., Calarco M., Pardini A., Marzollo P., Alfieri O., Messineo F. Oxidative stress during reperfusion of human hearts: potential sources of oxygen free radicals. Cardiovasc Res. 1995 Jan;29(1):118–125. [PubMed] [Google Scholar]
  10. Ferrari R., Alfieri O., Curello S., Ceconi C., Cargnoni A., Marzollo P., Pardini A., Caradonna E., Visioli O. Occurrence of oxidative stress during reperfusion of the human heart. Circulation. 1990 Jan;81(1):201–211. doi: 10.1161/01.cir.81.1.201. [DOI] [PubMed] [Google Scholar]
  11. Friedl H. P., Till G. O., Trentz O., Ward P. A. Role of oxygen radicals in tourniquet-related ischemia-reperfusion injury of human patients. Klin Wochenschr. 1991 Dec 15;69(21-23):1109–1112. doi: 10.1007/BF01645168. [DOI] [PubMed] [Google Scholar]
  12. Friedl H. P., Till G. O., Trentz O., Ward P. A. Roles of histamine, complement and xanthine oxidase in thermal injury of skin. Am J Pathol. 1989 Jul;135(1):203–217. [PMC free article] [PubMed] [Google Scholar]
  13. Fukushima N., Shirakura R., Nakata S., Kaneko M., Miyagawa S., Kitagawa S., Chang J., Amemiya A., Matsumiya G., Matsuda H. Effects of terminal cardioplegia with leukocyte-depleted blood on myocardial adenosine triphosphate in heart grafts preserved for 24 hours. Transplant Proc. 1992 Aug;24(4):1489–1490. [PubMed] [Google Scholar]
  14. Grech E. D., Baines M., Steyn R., Faragher E. B., Page R. D., Fabri B. M., Ramsdale D. R., Rashid A. Evidence that continuous normothermic blood cardioplegia offers better myocardial protection than intermittent hypothermic cardioplegia. Br Heart J. 1995 Nov;74(5):517–521. doi: 10.1136/hrt.74.5.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Harlan J. M. Leukocyte-endothelial interactions. Blood. 1985 Mar;65(3):513–525. [PubMed] [Google Scholar]
  16. Kloner R. A., Przyklenk K., Whittaker P. Deleterious effects of oxygen radicals in ischemia/reperfusion. Resolved and unresolved issues. Circulation. 1989 Nov;80(5):1115–1127. doi: 10.1161/01.cir.80.5.1115. [DOI] [PubMed] [Google Scholar]
  17. Kooij A. A re-evaluation of the tissue distribution and physiology of xanthine oxidoreductase. Histochem J. 1994 Dec;26(12):889–915. [PubMed] [Google Scholar]
  18. Korchak H. M., Vienne K., Rutherford L. E., Weissmann G. Neutrophil stimulation: receptor, membrane, and metabolic events. Fed Proc. 1984 Sep;43(12):2749–2754. [PubMed] [Google Scholar]
  19. Lazzarino G., Raatikainen P., Nuutinen M., Nissinen J., Tavazzi B., Di Pierro D., Giardina B., Peuhkurinen K. Myocardial release of malondialdehyde and purine compounds during coronary bypass surgery. Circulation. 1994 Jul;90(1):291–297. doi: 10.1161/01.cir.90.1.291. [DOI] [PubMed] [Google Scholar]
  20. Lucchesi B. R., Mullane K. M. Leukocytes and ischemia-induced myocardial injury. Annu Rev Pharmacol Toxicol. 1986;26:201–224. doi: 10.1146/annurev.pa.26.040186.001221. [DOI] [PubMed] [Google Scholar]
  21. Lunec J. Free radicals: their involvement in disease processes. Ann Clin Biochem. 1990 May;27(Pt 3):173–182. doi: 10.1177/000456329002700301. [DOI] [PubMed] [Google Scholar]
  22. McCoy R. N., Hill K. E., Ayon M. A., Stein J. H., Burk R. F. Oxidant stress following renal ischemia: changes in the glutathione redox ratio. Kidney Int. 1988 Apr;33(4):812–817. doi: 10.1038/ki.1988.72. [DOI] [PubMed] [Google Scholar]
  23. Menasche P., Grousset C., Gauduel Y., Piwnica A. A comparative study of free radical scavengers in cardioplegic solutions. Improved protection with peroxidase. J Thorac Cardiovasc Surg. 1986 Aug;92(2):264–271. [PubMed] [Google Scholar]
  24. Menasché P., Pasquier C., Bellucci S., Lorente P., Jaillon P., Piwnica A. Deferoxamine reduces neutrophil-mediated free radical production during cardiopulmonary bypass in man. J Thorac Cardiovasc Surg. 1988 Oct;96(4):582–589. [PubMed] [Google Scholar]
  25. Mullane K. M., Read N., Salmon J. A., Moncada S. Role of leukocytes in acute myocardial infarction in anesthetized dogs: relationship to myocardial salvage by anti-inflammatory drugs. J Pharmacol Exp Ther. 1984 Feb;228(2):510–522. [PubMed] [Google Scholar]
  26. Mullane K. M., Salmon J. A., Kraemer R. Leukocyte-derived metabolites of arachidonic acid in ischemia-induced myocardial injury. Fed Proc. 1987 May 15;46(7):2422–2433. [PubMed] [Google Scholar]
  27. Ogilvie A. C., Groeneveld A. B., Straub J. P., Thijs L. G. Plasma lipid peroxides and antioxidants in human septic shock. Intensive Care Med. 1991;17(1):40–44. doi: 10.1007/BF01708408. [DOI] [PubMed] [Google Scholar]
  28. Oosthuizen M. M., Nel L., Myburgh J. A., Crookes R. L. Purification of undegraded ceruloplasmin from outdated human plasma. Anal Biochem. 1985 Apr;146(1):1–6. doi: 10.1016/0003-2697(85)90386-0. [DOI] [PubMed] [Google Scholar]
  29. Paroni R., De Vecchi E., Cighetti G., Arcelloni C., Fermo I., Grossi A., Bonini P. HPLC with o-phthalaldehyde precolumn derivatization to measure total, oxidized, and protein-bound glutathione in blood, plasma, and tissue. Clin Chem. 1995 Mar;41(3):448–454. [PubMed] [Google Scholar]
  30. Pearl J. M., Drinkwater D. C., Laks H., Capouya E. R., Gates R. N. Leukocyte-depleted reperfusion of transplanted human hearts: a randomized, double-blind clinical trial. J Heart Lung Transplant. 1992 Nov-Dec;11(6):1082–1092. [PubMed] [Google Scholar]
  31. Romson J. L., Hook B. G., Kunkel S. L., Abrams G. D., Schork M. A., Lucchesi B. R. Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog. Circulation. 1983 May;67(5):1016–1023. doi: 10.1161/01.cir.67.5.1016. [DOI] [PubMed] [Google Scholar]
  32. Ward P. A., Hill J. H. C5 chemotactic fragments produced by an enzyme in lysosomal granules of neutrophils. J Immunol. 1970 Mar;104(3):535–543. [PubMed] [Google Scholar]
  33. Ward P. A., Till G. O., Hatherill J. R., Annesley T. M., Kunkel R. G. Systemic complement activation, lung injury, and products of lipid peroxidation. J Clin Invest. 1985 Aug;76(2):517–527. doi: 10.1172/JCI112001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Westlin W., Mullane K. M. Alleviation of myocardial stunning by leukocyte and platelet depletion. Circulation. 1989 Dec;80(6):1828–1836. doi: 10.1161/01.cir.80.6.1828. [DOI] [PubMed] [Google Scholar]
  35. Wilson I. C., Gardner T. J., DiNatale J. M., Gillinov A. M., Curtis W. E., Cameron D. E. Temporary leukocyte depletion reduces ventricular dysfunction during prolonged postischemic reperfusion. J Thorac Cardiovasc Surg. 1993 Nov;106(5):805–810. [PubMed] [Google Scholar]

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