Targeting the Pathological Myocardium

  • Ban-An Khaw
Chapter

Abstract

The rationale for targeting the pathological myocardium is to enable development of better diagnostic modalities or to enhance therapeutic interventions. Since the heart is an end-differentiated organ that has no substantial regenerative properties, any injury to the heart could potentially lead to high morbidity and mortality. The causes of myocardial injury are varied. Acute myocardial infarction results in oncotic myocardial cell death, whereas cardiomyopathies are now believed to be associated primarily with apoptotic myocardial cell death. If these myocardial disorders can be targeted specifically for early diagnosis, then morbidity and mortality may be reduced and novel therapeutic interventions may result in decreasing the injury to the heart. This chapter will focus primarily on targeting the oncotic myocardium. Targeting the apoptotic myocardium will not be considered in detail, but an introduction to the latest advances will be provided.

Keywords

Acute Myocardial Infarction Right Ventricular Leave Anterior Oblique Cell Membrane Disruption Antimyosin Antibody 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Pasternak RC, Braunwald E. Acute myocardial infarction. In Harrison’s Principles of Internal Medicine. Eds. Isselbacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci AS, Kasper DL. McGraw-Hill Inc. New York. 13th edition. 1994: 1066.Google Scholar
  2. 2.
    McCaarthy BD, Beshansky JR, D’Agostino RB, Selker HP. Missed diagnosis of acute myocardial infarction in the emergency department: Results from a multicenter study. Ann Emerg Med. 1993; 22: 579.Google Scholar
  3. 3.
    Khaw BA, Beller GA, Haber E, Smith TW. Localization of cardiac myosin-specific antibody in myocardial infarction. J Clin Invest. 1976; 58: 439–446.CrossRefGoogle Scholar
  4. 4.
    Khaw BA, Gold HK, Leinbach RC, Fallon JT, Strauss HW, Pohost GM, Haber E. Early imaging of experimental myocardial infarction by intracoronary administration of 131I-labeled anticardiac myosin (Fab’)2 fragments. Circulation. 1978; 58: 1137 1142.Google Scholar
  5. 5.
    Khaw BA, Petrov A, Narula J. Complementary roles of antibody affinity and specificity in in vivo diagnostic cardiovascular Targeting: How specific is antimyosin for irreversible myocardial damage? J Nucl Cardiol 1999; 6: 316–23.CrossRefGoogle Scholar
  6. 6.
    Khaw BA, Scott J, Fallon JT, Haber E, Homcy C. Myocardial injury: Quantitation by cell sorting initiated with anti-myosin fluorescent spheres. Science. 1982; 217: 1050–1053.CrossRefGoogle Scholar
  7. 7.
    Khaw BA, Strauss HW, Pohost GM, Fallon JT, Katus HA Haber E. The relationship of immediate and delayed thallium-201 distribution to localization of I-125antimyosin antibody in acute experimental myocardial infarction. Am J Cardiol. 1983; 51: 1428–1432.CrossRefGoogle Scholar
  8. 8.
    Khaw BA, Mousa S. Comparative Assessment of Experimental Myocardial Infarction with Tc-99m Hexakis-t-Butyl-Isonitrile (Sestamibi), In-111 antimyosin and T1–201. Nuclear Medicine Communications. 1991;12:853–863..Google Scholar
  9. 9.
    Khaw BA, Yasuda T, Gold HK, Leinbach RC, Johns JA, Kanke M, Barlai-Kovach M, Strauss HW, Haber E. Acute myocardial infarct imaging with Indium-111labeled monoclonal antimyosin Fab. J Nucl Med. 1987; 28: 1671–1678.Google Scholar
  10. 10.
    Johnson LL, Seldin DW, Becker LC, LaFrance ND, Liberman HA, James C, Mattis JA, Dean RT, Brown J, Reiter A, Arneson V, Cannon PJ, Berger HJ. Antimyosin imaging in acute transmural myocardial infarction: results of a multicenter clinical trial. J Am Coll Cardiol 1989; 13: 27.CrossRefGoogle Scholar
  11. 11.
    Johnson LL, Seldin DW, Becker LC, LaFrance ND, Liberman HA, James C, Mattis JA, Dean RT, Brown J, Reiter A, Arneson V, Cannon PJ, Berger HJ. Antimyosin imaging in acute transmural myocardial infraction: results of a multicenter clinical trial. J Am Coll Cardiol 1989; 13: 27–35.CrossRefGoogle Scholar
  12. 12.
    Berger H, Lahiri A, Leppo J, Makler T, Maddahi J, Mintz G, Strauss HW. Antimyosin imaging in patients with ischemic chest pain: initial results of phase III multicenter trial. J Nucl Med 1988; 28: 805 (Abstract).Google Scholar
  13. 13.
    Jain D, Lahiri A, Crawley JCw, Raftery EB. Indium-111 antimyosin imaging in a patient with acute myocardial infarction: postmortem correlation between histopathologic and autoradiographic extent of myocardial necrosis. Am J Card Imaging. 1988; 2: 158–161.Google Scholar
  14. 14.
    Hendel RC, McSherry BA, Leppo JA. Myocardial uptake of indium-111 labeled antimyosin in acute subendocardial infarction: clinical, histochemicaland autoradiographic correlation of myocardial necrosis. J Nucl med. 1990; 31: 1851–1853.Google Scholar
  15. 15.
    Jain D, Lahiri A, Raftery E. Immunoscintigraphy for detecting acute myocardial infarction without electrocardiographic changes. Br Med J. 1990; 300: 151–153.CrossRefGoogle Scholar
  16. 16.
    Johnson LL, Seldin DW, Tresgallo ME, et al. Right ventricular infarction and function from dual isotope indium-111 antimyosin/thallium-201 SPECT and gated blood pool scintigraphy [abst]. J Nucl Med. 1991; 32: 1018.Google Scholar
  17. 17.
    van Vlies B, van Royen ED, Visser CA, et al. Frequency of myocardial indium-111 antimyosin uptake after uncomplicated coronary bypass surgery. AM J Cardiol 1990; 66: 1191–1195.CrossRefGoogle Scholar
  18. 18.
    Hultgren HN, Shettigar UR, Pfeifer JF, Angell WW. Acute myocardial infarction ischemic injury during surgery for cornary artery disease. Am Heart J. 1977; 94: 146–153.CrossRefGoogle Scholar
  19. 19.
    Bulkley BH, Hutchins GM. Myocardial consequences of coronary artery bypass graft surgery: the paradox of necrosis in areas of revascularization. Circ. 1977; 56: 906–913.CrossRefGoogle Scholar
  20. 20.
    Califf RM, Topol EJ, George BS, et at. One-year outcome after therapy with tissue plasminogen activator-, Report from the Thrombolysis and Angioplasty in Myocardial Infarction trial. Am Heart J 119; 1990; 777.CrossRefGoogle Scholar
  21. 21.
    The TIMI Study Group. Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute myocardial infarction: Results of the Thrombolysis in Myocardial Infarction (TIMI) Phase 11 trial. NEngi JMed 320;1989,618.).Google Scholar
  22. 22.
    Pak KY, Nedelman MA, Kanke M, Khaw BA, Mattis JA, Strauss HW, Dean RT, Berger HJ. An Instant Method for Labeling Antimyosin Fab’ with Technetium-99m: Evaluation in an Experimental Myocardial Infarct Model. J Nucl Med. 1992; 33 (1): 144–149.Google Scholar
  23. 23.
    Khaw BA, Nakazawa A, O’Donnell, Pak KY, Narula J. Avidity of 99mTc-glucarate for the necrotic myocardium: In vivo and in vitro assessment. J Nucl Cardiol 1997; 4: 283–290.CrossRefGoogle Scholar
  24. 24.
    Fornet b, Yasuda T, Wilkinson R, Ahmed M, Moore R, Khaw BA, Fischman AJ, Strauss HW. Detection of acute cardiac injury with technetium-99m glucaric acid. J nucl Med. 1989; 30: 1743.Google Scholar
  25. 25.
    Orlandi C, Crane PD, Edwards DS, Platts SH, Bernard L, Lazewatsky J, Thoolen MJ. Early scintigraphie detection of experimental myocardial infarction in dogs with technetium-99m-glucaric acid. J Nucl Med. 1991; 32: 263–268.Google Scholar
  26. 26.
    Narula J, Petrov A, Pak KY, Lister BC, Khaw BA. Very early noninvasive detection of acute experimental non-reperfused myocardial infarction with technetium-99mlabeled glucarate. Circ 1997; 95: 1577–1584.CrossRefGoogle Scholar
  27. 27.
    Ohtani H, Callahan RJ, Khaw BA, Fischman AJ, Wilkinson RA, Strauss HW. Comparison of technetium-99m-glucarate and thallium-201 for the identification of acute myocardial infarction in rats. J Nucl Med. 1992; 33: 1988–1993.Google Scholar
  28. 28.
    Khaw BA. daSilva J, Petrov A, Hartner W. In-111 antimyosin and Tc-99m glucaric acid for non-invasive identification of oncotic and apoptotic myocardial necrosis. J Nucl Cardiol. (Submitted).Google Scholar
  29. 29.
    Mariani G, Villa G, Rossettin PF, Spallarossa P, Bezante GP, Brunelli C, Pak KY, Khaw BA, Strauss HW. Detection of acute myocardial infarction with 99mTclabeled D-glucaric acid: imaging in patients presenting with acute chest pain. J Nucl Med. 1999; 40: 1832–1839.Google Scholar
  30. 30.
    Narula J, Acio ER, Narula N, Samuels LE, Fyfe B, Wood D, Fitzpatrick JM, Raghunath PN, Tomaszewski JE, Kelly C, Steinmetz N, Green A, Tait JF, Leppo J, Blankenberg FG, Jain D, Strauss HW. Annexin-V imaging for noninvasive detection of cardiac allograft rejection. Nat Med 2001 Dec; 7 (12): 1347–52CrossRefGoogle Scholar
  31. 31.
    Torchilin VP, Khaw BA, Smirnov VN, Haber E. Preservation of antimyosin antibody activity after covalent coupling to liposomes. Biochem Biophys Res Comm. 1979; 89: 1114–1119.CrossRefGoogle Scholar
  32. 32.
    Torchilin VP, Klibanov AL, Huang L, O’Donnell S, Nossiff ND, Khaw BA. Targeted accumulation of PEG-coated immunoliposomes in infarcted myocardium in rabbits. FASEB J. 1992; 6: 2716–2719.Google Scholar
  33. 33.
    Khaw BA, Torchilin VP, Vural I, Narula J. Plug and Seal: Prevention of Hypoxic Cardiocyte Death by Sealing Membrane Lesions with Antimyosin-Liposomes. Nature Medicine 1995; 1 (11): 1195–1198.CrossRefGoogle Scholar
  34. 34.
    Khaw BA, daSliva J, Vural I, Narula J, Torchilin VP. Intracytoplasmic gene delivery for in vitro transfection with cytoskeleton-specific immunoliposomes. J Cont. Release, 2001; 75: 199–210.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Ban-An Khaw
    • 1
  1. 1.Bouve College of Health Sciences, School of Pharmacy, Department of Pharmaceutical SciencesNortheastern UniversityBostonUSA

Personalised recommendations