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British Heart Journal logoLink to British Heart Journal
. 1993 Feb;69(2):114–120. doi: 10.1136/hrt.69.2.114

Free radical activity and left ventricular function after thrombolysis for acute infarction.

S W Davies 1, K Ranjadayalan 1, D G Wickens 1, T L Dormandy 1, V Umachandran 1, A D Timmis 1
PMCID: PMC1024936  PMID: 8435235

Abstract

BACKGROUND--Experimental data suggest that reperfusion injury involving free radicals contributes to the impairment of left ventricular function after successful thrombolysis. METHODS--In 72 patients presenting with acute myocardial infarction, markers of free radical activity were measured before streptokinase and two hours later. Thiobarbituric acid reactive material (TBA-RM) reflects lipid peroxidation by free radicals, and the concentration of plasma total thiols (34 patients) reflects oxidative stress. Coronary arteriography was performed at 18-72 hours after thrombolysis to determine coronary patency, and left ventricular function was assessed by ventriculography and from QRS scoring of the electrocardiogram. RESULTS--The infarct related artery was patent (Thrombolysis In Myocardial Infarction Trial grade 2 or better) in 60 (83%) and occluded in 12. In the 60 with a patent artery, the concentration of TBA-RM increased after streptokinase by (mean (SD)) 9.2 (14.0) nmol/g albumin, whereas in the 12 with an occluded artery TBA-RM decreased by 7.0 (11.3) nmol/g albumin (p < 0.01 between groups). In those with a patent artery the rise in TBA-RM associated with thrombolysis correlated with left ventricular ejection fraction (R = -0.41, p < 0.002), and with the QRS score (R = +0.38, p = 0.003). Plasma total thiol concentrations decreased by 12.7 (31.1) mumol/l in those with a patent artery, and this decrease associated with thrombolysis correlated with left ventricular ejection fraction (R = +0.39, p < 0.02) but not with the QRS score (R = -0.2, NS). CONCLUSIONS--These findings suggest that reperfusion injury mediated by free radicals may be of clinical importance in humans.

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Selected References

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  1. Barsacchi R., Pelosi G., Camici P., Bonaldo L., Maiorino M., Ursini F. Glutathione depletion increases chemiluminescence emission and lipid peroxidation in the heart. Biochim Biophys Acta. 1984 Jul 20;804(3):356–360. doi: 10.1016/0167-4889(84)90139-3. [DOI] [PubMed] [Google Scholar]
  2. Bassand J. P., Machecourt J., Cassagnes J., Anguenot T., Lusson R., Borel E., Peycelon P., Wolf E., Ducellier D. Multicenter trial of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction: effects on infarct size and left ventricular function. J Am Coll Cardiol. 1989 Apr;13(5):988–997. doi: 10.1016/0735-1097(89)90249-0. [DOI] [PubMed] [Google Scholar]
  3. Beller G. A. Noninvasive assessment of myocardial salvage after coronary reperfusion: a perpetual quest of nuclear cardiology. J Am Coll Cardiol. 1989 Oct;14(4):874–876. doi: 10.1016/0735-1097(89)90457-9. [DOI] [PubMed] [Google Scholar]
  4. Borer J. S., Rosing D. R., Miller R. H., Stark R. M., Kent K. M., Bacharach S. L., Green M. V., Lake C. R., Cohen H., Holmes D. Natural history of left ventricular function during 1 year after acute myocardial infarction: comparison with clinical, electrocardiographic and biochemical determinations. Am J Cardiol. 1980 Jul;46(1):1–12. doi: 10.1016/0002-9149(80)90598-6. [DOI] [PubMed] [Google Scholar]
  5. Borow K. M., Green L. H., Mann T., Sloss L. J., Braunwald E., Collins J. J., Cohn L., Grossman W. End-systolic volume as a predictor of postoperative left ventricular performance in volume overload from valvular regurgitation. Am J Med. 1980 May;68(5):655–663. doi: 10.1016/0002-9343(80)90251-x. [DOI] [PubMed] [Google Scholar]
  6. Braunwald E., Kloner R. A. Myocardial reperfusion: a double-edged sword? J Clin Invest. 1985 Nov;76(5):1713–1719. doi: 10.1172/JCI112160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Braunwald E., Kloner R. A. The stunned myocardium: prolonged, postischemic ventricular dysfunction. Circulation. 1982 Dec;66(6):1146–1149. doi: 10.1161/01.cir.66.6.1146. [DOI] [PubMed] [Google Scholar]
  8. Brunelli C., Cristofani R., L'Abbate A. Long-term survival in medically treated patients with ischaemic heart disease and prognostic importance of clinical and electrocardiographic data (the Italian CNR Multicentre Prospective Study OD1). Eur Heart J. 1989 Apr;10(4):292–303. doi: 10.1093/oxfordjournals.eurheartj.a059486. [DOI] [PubMed] [Google Scholar]
  9. Burrell C. J., Blake D. R. Reactive oxygen metabolites and the human myocardium. Br Heart J. 1989 Jan;61(1):4–8. doi: 10.1136/hrt.61.1.4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chesebro J. H., Knatterud G., Roberts R., Borer J., Cohen L. S., Dalen J., Dodge H. T., Francis C. K., Hillis D., Ludbrook P. Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation. 1987 Jul;76(1):142–154. doi: 10.1161/01.cir.76.1.142. [DOI] [PubMed] [Google Scholar]
  11. Davies S. W., Ranjadayalan K., Wickens D. G., Dormandy T. L., Timmis A. D. Lipid peroxidation associated with successful thrombolysis. Lancet. 1990 Mar 31;335(8692):741–743. doi: 10.1016/0140-6736(90)90866-4. [DOI] [PubMed] [Google Scholar]
  12. Davies S. W., Underwood S. M., Wickens D. G., Feneck R. O., Dormandy T. L., Walesby R. K. Systemic pattern of free radical generation during coronary bypass surgery. Br Heart J. 1990 Oct;64(4):236–240. doi: 10.1136/hrt.64.4.236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dousset J. C., Trouilh M., Foglietti M. J. Plasma malonaldehyde levels during myocardial infarction. Clin Chim Acta. 1983 Apr 25;129(3):319–322. doi: 10.1016/0009-8981(83)90035-9. [DOI] [PubMed] [Google Scholar]
  14. ELLMAN G. L. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959 May;82(1):70–77. doi: 10.1016/0003-9861(59)90090-6. [DOI] [PubMed] [Google Scholar]
  15. Ferreira R., Llesuy S., Milei J., Scordo D., Hourquebie H., Molteni L., de Palma C., Boveris A. Assessment of myocardial oxidative stress in patients after myocardial revascularization. Am Heart J. 1988 Feb;115(2):307–312. doi: 10.1016/0002-8703(88)90475-9. [DOI] [PubMed] [Google Scholar]
  16. Forman M. B., Puett D. W., Cates C. U., McCroskey D. E., Beckman J. K., Greene H. L., Virmani R. Glutathione redox pathway and reperfusion injury. Effect of N-acetylcysteine on infarct size and ventricular function. Circulation. 1988 Jul;78(1):202–213. doi: 10.1161/01.cir.78.1.202. [DOI] [PubMed] [Google Scholar]
  17. Fuster V., Gersh B. J., Giuliani E. R., Tajik A. J., Brandenburg R. O., Frye R. L. The natural history of idiopathic dilated cardiomyopathy. Am J Cardiol. 1981 Mar;47(3):525–531. doi: 10.1016/0002-9149(81)90534-8. [DOI] [PubMed] [Google Scholar]
  18. Garlick P. B., Davies M. J., Hearse D. J., Slater T. F. Direct detection of free radicals in the reperfused rat heart using electron spin resonance spectroscopy. Circ Res. 1987 Nov;61(5):757–760. doi: 10.1161/01.res.61.5.757. [DOI] [PubMed] [Google Scholar]
  19. Guarnieri C., Ferrari R., Visioli O., Caldarera C. M., Nayler W. G. Effect of alpha-tocopherol on hypoxic-perfused and reoxygenated rabbit heart muscle. J Mol Cell Cardiol. 1978 Oct;10(10):893–906. doi: 10.1016/0022-2828(78)90336-x. [DOI] [PubMed] [Google Scholar]
  20. Guarnieri C., Flamigni F., Caldarera C. M. Role of oxygen in the cellular damage induced by re-oxygenation of hypoxic heart. J Mol Cell Cardiol. 1980 Aug;12(8):797–808. doi: 10.1016/0022-2828(80)90081-4. [DOI] [PubMed] [Google Scholar]
  21. Guerci A. D., Gerstenblith G., Brinker J. A., Chandra N. C., Gottlieb S. O., Bahr R. D., Weiss J. L., Shapiro E. P., Flaherty J. T., Bush D. E. A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty. N Engl J Med. 1987 Dec 24;317(26):1613–1618. doi: 10.1056/NEJM198712243172601. [DOI] [PubMed] [Google Scholar]
  22. Hammond B., Hess M. L. The oxygen free radical system: potential mediator of myocardial injury. J Am Coll Cardiol. 1985 Jul;6(1):215–220. doi: 10.1016/s0735-1097(85)80278-3. [DOI] [PubMed] [Google Scholar]
  23. Hearse D. J., Tosaki A. Free radicals and calcium: simultaneous interacting triggers as determinants of vulnerability to reperfusion-induced arrhythmias in the rat heart. J Mol Cell Cardiol. 1988 Mar;20(3):213–223. doi: 10.1016/s0022-2828(88)80054-3. [DOI] [PubMed] [Google Scholar]
  24. Hess M. L., Okabe E., Kontos H. A. Proton and free oxygen radical interaction with the calcium transport system of cardiac sarcoplasmic reticulum. J Mol Cell Cardiol. 1981 Aug;13(8):767–772. doi: 10.1016/0022-2828(81)90258-3. [DOI] [PubMed] [Google Scholar]
  25. Kennedy J. W., Martin G. V., Davis K. B., Maynard C., Stadius M., Sheehan F. H., Ritchie J. L. The Western Washington Intravenous Streptokinase in Acute Myocardial Infarction Randomized Trial. Circulation. 1988 Feb;77(2):345–352. doi: 10.1161/01.cir.77.2.345. [DOI] [PubMed] [Google Scholar]
  26. Mathur V. S., Guinn G. A., Burris W. H., 3rd Maximal revascularization (reperfusion) in intact conscious dogs after 2 to 5 hours of coronary occlusion. Am J Cardiol. 1975 Aug;36(2):252–261. doi: 10.1016/0002-9149(75)90534-2. [DOI] [PubMed] [Google Scholar]
  27. Meerson F. Z., Abdikaliev N. A., Golubeva L. Iu. Preduprezhdenie gipoksicheskogo povrezhdeniia serdtsa s pomoshch'iu antioksidanta iz klassa oksipiridinov. Biull Eksp Biol Med. 1981 Sep;92(9):281–283. [PubMed] [Google Scholar]
  28. Olson H. G., Butman S. M., Piters K. M., Gardin J. M., Lyons K. P., Jones L., Chilazi G., Kumar K. L., Colombo A. A randomized controlled trial of intravenous streptokinase in evolving acute myocardial infarction. Am Heart J. 1986 Jun;111(6):1021–1029. doi: 10.1016/0002-8703(86)90001-3. [DOI] [PubMed] [Google Scholar]
  29. Ong L., Coromilas J., Zimmerman J. M., Green S., Padmanabhan V., Reiser P., Bigger J. T., Jr, Morrison J. A physiologically based model of creatine kinase-MB release in reperfusion of acute myocardial infarction. Am J Cardiol. 1989 Jul 1;64(1):11–15. doi: 10.1016/0002-9149(89)90645-0. [DOI] [PubMed] [Google Scholar]
  30. Palmeri S. T., Harrison D. G., Cobb F. R., Morris K. G., Harrell F. E., Ideker R. E., Selvester R. H., Wagner G. S. A QRS scoring system for assessing left ventricular function after myocardial infarction. N Engl J Med. 1982 Jan 7;306(1):4–9. doi: 10.1056/NEJM198201073060102. [DOI] [PubMed] [Google Scholar]
  31. RODKEY F. L. DIRECT SPECTROPHOTOMETRIC DETERMINATION OF ALBUMIN IN HUMAN SERUM. Clin Chem. 1965 Apr;11:478–487. [PubMed] [Google Scholar]
  32. Ranjadayalan K., Umachandran V., Davies S. W., Syndercombe-Court D., Gutteridge C. N., Timmis A. D. Thrombolytic treatment in acute myocardial infarction: neutrophil activation, peripheral leucocyte responses, and myocardial injury. Br Heart J. 1991 Jul;66(1):10–14. doi: 10.1136/hrt.66.1.10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Reimer K. A., Lowe J. E., Rasmussen M. M., Jennings R. B. The wavefront phenomenon of ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs. Circulation. 1977 Nov;56(5):786–794. doi: 10.1161/01.cir.56.5.786. [DOI] [PubMed] [Google Scholar]
  34. Sandler H., Dodge H. T. The use of single plane angiocardiograms for the calculation of left ventricular volume in man. Am Heart J. 1968 Mar;75(3):325–334. doi: 10.1016/0002-8703(68)90089-6. [DOI] [PubMed] [Google Scholar]
  35. Schreiber T. L., Miller D. H., Silvasi D. A., Moses J. W., Borer J. S. Randomized double-blind trial of intravenous streptokinase for acute myocardial infarction. Am J Cardiol. 1986 Jul 1;58(1):47–52. doi: 10.1016/0002-9149(86)90239-0. [DOI] [PubMed] [Google Scholar]
  36. Van de Werf F. Discrepancies between the effects of coronary reperfusion on survival and left ventricular function. Lancet. 1989 Jun 17;1(8651):1367–1369. doi: 10.1016/s0140-6736(89)92812-2. [DOI] [PubMed] [Google Scholar]
  37. Vlietstra R. E., Frye R. L., Kronmal R. A., Sim D. A., Tristani F. E., Killip T., 3rd Risk factors and angiographic coronary artery disease: a report from the coronary artery surgery study (CASS). Circulation. 1980 Aug;62(2):254–261. doi: 10.1161/01.cir.62.2.254. [DOI] [PubMed] [Google Scholar]
  38. White H. D., Norris R. M., Brown M. A., Brandt P. W., Whitlock R. M., Wild C. J. Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation. 1987 Jul;76(1):44–51. doi: 10.1161/01.cir.76.1.44. [DOI] [PubMed] [Google Scholar]
  39. White H. D., Norris R. M., Brown M. A., Takayama M., Maslowski A., Bass N. M., Ormiston J. A., Whitlock T. Effect of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction. N Engl J Med. 1987 Oct 1;317(14):850–855. doi: 10.1056/NEJM198710013171402. [DOI] [PubMed] [Google Scholar]
  40. Yagi K. A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med. 1976 Apr;15(2):212–216. doi: 10.1016/0006-2944(76)90049-1. [DOI] [PubMed] [Google Scholar]
  41. Yusuf S., Collins R., Peto R., Furberg C., Stampfer M. J., Goldhaber S. Z., Hennekens C. H. Intravenous and intracoronary fibrinolytic therapy in acute myocardial infarction: overview of results on mortality, reinfarction and side-effects from 33 randomized controlled trials. Eur Heart J. 1985 Jul;6(7):556–585. doi: 10.1093/oxfordjournals.eurheartj.a061905. [DOI] [PubMed] [Google Scholar]

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