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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1994 Apr;111(4):1123–1128. doi: 10.1111/j.1476-5381.1994.tb14861.x

Effect of duration of ischaemia on reduction of myocardial infarct size by inhibition of neutrophil accumulation using an anti-CD18 monoclonal antibody.

F M Williams 1, M Kus 1, K Tanda 1, T J Williams 1
PMCID: PMC1910128  PMID: 7913371

Abstract

1. Neutrophil accumulation is a characteristic feature of the inflammatory response in myocardial tissue which has undergone a period of ischaemia. The aim of this study was to examine whether inhibition of myocardial neutrophil infiltration, using an antibody to the CD18 leukocyte adhesion molecule, was effective in reducing infarct size in anaesthetized rabbits. 2. Anaesthetized rabbits underwent coronary artery occlusion (CAO) for periods of 30 or 45 min followed by reperfusion for 3 h. Animals were treated intravenously 10 min prior to reperfusion with IB4, a monoclonal antibody to CD18 (1 mg kg-1) or saline (1 ml kg-1). In one group undergoing 45 min CAO, a control antibody, OKMI (1 mg kg-1) was given. 3. Following either 30 or 45 min of CAO, administration of IB4 resulted in a < 75% inhibition in neutrophil accumulation in the area at risk myocardium (AR) compared with control animals. 4. With the 30 min occlusion period, IB4 significantly reduced myocardial infarct size, 27.2 +/- 3.2% vs 67.4 +/- 5.6% in the saline control group (n = 5 P < 0.01). In contrast, IB4 did not reduce infarct size following a 45 min period of ischaemia. 5. In the same animals administration of IB4 significantly inhibited oedema formation in skin elicited by intradermal administration of the neutrophil chemoattractant f-Met-Leu-Phe, but had no effect on coronary microvascular plasma protein leakage in the AR. 6. Our results indicate that infiltrating neutrophils exacerbate tissue injury following a relatively short, 30 min period of myocardial ischaemia in the rabbit.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Arfors K. E., Lundberg C., Lindbom L., Lundberg K., Beatty P. G., Harlan J. M. A monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo. Blood. 1987 Jan;69(1):338–340. [PubMed] [Google Scholar]
  2. Bednar M., Smith B., Pinto A., Mullane K. M. Nafazatrom-induced salvage of ischemic myocardium in anesthetized dogs is mediated through inhibition of neutrophil function. Circ Res. 1985 Jul;57(1):131–141. doi: 10.1161/01.res.57.1.131. [DOI] [PubMed] [Google Scholar]
  3. Chatelain P., Latour J. G., Tran D., de Lorgeril M., Dupras G., Bourassa M. Neutrophil accumulation in experimental myocardial infarcts: relation with extent of injury and effect of reperfusion. Circulation. 1987 May;75(5):1083–1090. doi: 10.1161/01.cir.75.5.1083. [DOI] [PubMed] [Google Scholar]
  4. Harlan J. M., Killen P. D., Senecal F. M., Schwartz B. R., Yee E. K., Taylor R. F., Beatty P. G., Price T. H., Ochs H. D. The role of neutrophil membrane glycoprotein GP-150 in neutrophil adherence to endothelium in vitro. Blood. 1985 Jul;66(1):167–178. [PubMed] [Google Scholar]
  5. Jolly S. R., Kane W. J., Hook B. G., Abrams G. D., Kunkel S. L., Lucchesi B. R. Reduction of myocardial infarct size by neutrophil depletion: effect of duration of occlusion. Am Heart J. 1986 Oct;112(4):682–690. doi: 10.1016/0002-8703(86)90461-8. [DOI] [PubMed] [Google Scholar]
  6. Litt M. R., Jeremy R. W., Weisman H. F., Winkelstein J. A., Becker L. C. Neutrophil depletion limited to reperfusion reduces myocardial infarct size after 90 minutes of ischemia. Evidence for neutrophil-mediated reperfusion injury. Circulation. 1989 Dec;80(6):1816–1827. doi: 10.1161/01.cir.80.6.1816. [DOI] [PubMed] [Google Scholar]
  7. Lo S. K., Detmers P. A., Levin S. M., Wright S. D. Transient adhesion of neutrophils to endothelium. J Exp Med. 1989 May 1;169(5):1779–1793. doi: 10.1084/jem.169.5.1779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lundberg C., Wright S. D. Relation of the CD11/CD18 family of leukocyte antigens to the transient neutropenia caused by chemoattractants. Blood. 1990 Sep 15;76(6):1240–1245. [PubMed] [Google Scholar]
  9. Ma X. L., Tsao P. S., Lefer A. M. Antibody to CD-18 exerts endothelial and cardiac protective effects in myocardial ischemia and reperfusion. J Clin Invest. 1991 Oct;88(4):1237–1243. doi: 10.1172/JCI115427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Maxwell M. P., Hearse D. J., Yellon D. M. Species variation in the coronary collateral circulation during regional myocardial ischaemia: a critical determinant of the rate of evolution and extent of myocardial infarction. Cardiovasc Res. 1987 Oct;21(10):737–746. doi: 10.1093/cvr/21.10.737. [DOI] [PubMed] [Google Scholar]
  11. Mullane K. M., Kraemer R., Smith B. Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium. J Pharmacol Methods. 1985 Nov;14(3):157–167. doi: 10.1016/0160-5402(85)90029-4. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Nourshargh S., Rampart M., Hellewell P. G., Jose P. J., Harlan J. M., Edwards A. J., Williams T. J. Accumulation of 111In-neutrophils in rabbit skin in allergic and non-allergic inflammatory reactions in vivo. Inhibition by neutrophil pretreatment in vitro with a monoclonal antibody recognizing the CD18 antigen. J Immunol. 1989 May 1;142(9):3193–3198. [PubMed] [Google Scholar]
  14. Reimer K. A., Jennings R. B., Cobb F. R., Murdock R. H., Greenfield J. C., Jr, Becker L. C., Bulkley B. H., Hutchins G. M., Schwartz R. P., Jr, Bailey K. R. Animal models for protecting ischemic myocardium: results of the NHLBI Cooperative Study. Comparison of unconscious and conscious dog models. Circ Res. 1985 May;56(5):651–665. doi: 10.1161/01.res.56.5.651. [DOI] [PubMed] [Google Scholar]
  15. Reimer K. A., Murry C. E., Richard V. J. The role of neutrophils and free radicals in the ischemic-reperfused heart: why the confusion and controversy? J Mol Cell Cardiol. 1989 Dec;21(12):1225–1239. doi: 10.1016/0022-2828(89)90669-x. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Romson J. L., Hook B. G., Rigot V. H., Schork M. A., Swanson D. P., Lucchesi B. R. The effect of ibuprofen on accumulation of indium-111-labeled platelets and leukocytes in experimental myocardial infarction. Circulation. 1982 Nov;66(5):1002–1011. doi: 10.1161/01.cir.66.5.1002. [DOI] [PubMed] [Google Scholar]
  18. Rubin B. B., Smith A., Liauw S., Isenman D., Romaschin A. D., Walker P. M. Complement activation and white cell sequestration in postischemic skeletal muscle. Am J Physiol. 1990 Aug;259(2 Pt 2):H525–H531. doi: 10.1152/ajpheart.1990.259.2.H525. [DOI] [PubMed] [Google Scholar]
  19. Simpson P. J., Fantone J. C., Mickelson J. K., Gallagher K. P., Lucchesi B. R. Identification of a time window for therapy to reduce experimental canine myocardial injury: suppression of neutrophil activation during 72 hours of reperfusion. Circ Res. 1988 Dec;63(6):1070–1079. doi: 10.1161/01.res.63.6.1070. [DOI] [PubMed] [Google Scholar]
  20. Simpson P. J., Mitsos S. E., Ventura A., Gallagher K. P., Fantone J. C., Abrams G. D., Schork M. A., Lucchesi B. R. Prostacyclin protects ischemic reperfused myocardium in the dog by inhibition of neutrophil activation. Am Heart J. 1987 Jan;113(1):129–137. doi: 10.1016/0002-8703(87)90020-2. [DOI] [PubMed] [Google Scholar]
  21. Simpson P. J., Todd R. F., 3rd, Fantone J. C., Mickelson J. K., Griffin J. D., Lucchesi B. R. Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mo1, anti-CD11b) that inhibits leukocyte adhesion. J Clin Invest. 1988 Feb;81(2):624–629. doi: 10.1172/JCI113364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Simpson P. J., Todd R. F., 3rd, Mickelson J. K., Fantone J. C., Gallagher K. P., Lee K. A., Tamura Y., Cronin M., Lucchesi B. R. Sustained limitation of myocardial reperfusion injury by a monoclonal antibody that alters leukocyte function. Circulation. 1990 Jan;81(1):226–237. doi: 10.1161/01.cir.81.1.226. [DOI] [PubMed] [Google Scholar]
  23. Tanaka M., Brooks S. E., Richard V. J., FitzHarris G. P., Stoler R. C., Jennings R. B., Arfors K. E., Reimer K. A. Effect of anti-CD18 antibody on myocardial neutrophil accumulation and infarct size after ischemia and reperfusion in dogs. Circulation. 1993 Feb;87(2):526–535. doi: 10.1161/01.cir.87.2.526. [DOI] [PubMed] [Google Scholar]
  24. Thornton J., Striplin S., Liu G. S., Swafford A., Stanley A. W., Van Winkle D. M., Downey J. M. Inhibition of protein synthesis does not block myocardial protection afforded by preconditioning. Am J Physiol. 1990 Dec;259(6 Pt 2):H1822–H1825. doi: 10.1152/ajpheart.1990.259.6.H1822. [DOI] [PubMed] [Google Scholar]
  25. Tuomanen E. I., Saukkonen K., Sande S., Cioffe C., Wright S. D. Reduction of inflammation, tissue damage, and mortality in bacterial meningitis in rabbits treated with monoclonal antibodies against adhesion-promoting receptors of leukocytes. J Exp Med. 1989 Sep 1;170(3):959–969. doi: 10.1084/jem.170.3.959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wallis W. J., Hickstein D. D., Schwartz B. R., June C. H., Ochs H. D., Beatty P. G., Klebanoff S. J., Harlan J. M. Monoclonal antibody-defined functional epitopes on the adhesion-promoting glycoprotein complex (CDw18) of human neutrophils. Blood. 1986 Apr;67(4):1007–1013. [PubMed] [Google Scholar]
  27. Wedmore C. V., Williams T. J. Control of vascular permeability by polymorphonuclear leukocytes in inflammation. Nature. 1981 Feb 19;289(5799):646–650. doi: 10.1038/289646a0. [DOI] [PubMed] [Google Scholar]
  28. Weiss S. J. Tissue destruction by neutrophils. N Engl J Med. 1989 Feb 9;320(6):365–376. doi: 10.1056/NEJM198902093200606. [DOI] [PubMed] [Google Scholar]
  29. Williams F. M., Collins P. D., Tannière-Zeller M., Williams T. J. The relationship between neutrophils and increased microvascular permeability in a model of myocardial ischaemia and reperfusion in the rabbit. Br J Pharmacol. 1990 Aug;100(4):729–734. doi: 10.1111/j.1476-5381.1990.tb14083.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wright S. D., Rao P. E., Van Voorhis W. C., Craigmyle L. S., Iida K., Talle M. A., Westberg E. F., Goldstein G., Silverstein S. C. Identification of the C3bi receptor of human monocytes and macrophages by using monoclonal antibodies. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5699–5703. doi: 10.1073/pnas.80.18.5699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. de Lorgeril M., Basmadjian A., Lavallée M., Clément R., Millette D., Rousseau G., Latour J. G. Influence of leukopenia on collateral flow, reperfusion flow, reflow ventricular fibrillation, and infarct size in dogs. Am Heart J. 1989 Mar;117(3):523–532. doi: 10.1016/0002-8703(89)90724-2. [DOI] [PubMed] [Google Scholar]

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