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Apoptotic myocardial degeneration in thrombotic thrombocytopenic purpura

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Abstract

The objective of this study was to determine whether the known myocardial degeneration in TTP is due to apoptosis. In TTP the heart is often involved, including the cardiac conduction system. Despite many platelet occlusions of small coronary arteries, there is little myocardial necrosis. Why the intermittent clinical episodes begin or end is unknown. Six hearts of patients dying with TTP were examined with routine and immunohistochemical stains. In addition to ventricular and atrial myocardium we examined the cardiac conduction system and coronary chemoreceptor. Numerous small coronary arteries were occluded with platelet thrombi in all these sites, including especially the sinus node, AV node and His bundle. The myocardial degeneration we found was conspicuously devoid of inflammation and the myocytes were relatively intact. These characteristics combined with TUNEL-positivity in the degenerating cells are typical of apoptosis. The focal degeneration in TTP is primarily apoptotic. Because circulating serotonin is carried by platelets and is released during aggregation, and because serotonin can cause a powerful cardiogenic hypertensive chemoreflex, we suggest that such a response may dislodge early platelet aggregations. Lessons from TTP may have special relevance for better understanding of myocardial reperfusion problems associated with angioplasty, thrombolysis and ischemic preconditioning.

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References

  1. Moake SL, Eisenstaedt. Thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome. In: Coleman RW, Hirsh J, Marder V, Salzman EW, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice, Third Edition. Philadelphia, PA (USA): J.B. Lippincott 1994: 1064–1075.

    Google Scholar 

  2. Shumak KH, Rock GA, Nair RC. Late relapses in patients successfully treated for thrombotic thrombocytopenic purpura. Ann Intern Med 1995; 122: 569–572.

    Google Scholar 

  3. James TN, Monto RW. Pathology of the cardiac conduction system in thrombotic thrombocytopenic purpura. Ann Intern Med 1966; 65: 37–43.

    Google Scholar 

  4. Ridolfi RL, Hutchins GM, Bell WR. The heart and cardiac conduction system in thrombotic thrombocytopenic purpura. Ann Intern Med 1979; 91: 357–363.

    Google Scholar 

  5. Burns ER, Zucker-Frankli D. Patts of tientbotic thrombocytopenic purpura on platelets and cultured vascular endothelial cells. Blood 1982; 60: 1030–1037.

    Google Scholar 

  6. Laurence J, Mitra D, Steiner M, Staiano-Coico L, Jaffe E. Plasma from patients with idiopathic and human immunodeficiency virus-associated thrombotic thrombocytopenic purpura induces apoptosis in microvascular endothelial cells. Blood 1996; 87: 3245–3254.

    Google Scholar 

  7. Gore I. Disseminated arteriolar and capillary platelet thrombosis. Am J Pathol 1950; 26: 155–167.

    Google Scholar 

  8. Baroldi G, Manion WC. Microcirculatory disturbances and human myocardial infarction. Am Heart J 1967; 74: 173–178.

    Google Scholar 

  9. James TN. Anatomy of the Coronary Arteries. Hagerstown, MD (USA): Harper Brothers, 1961.

    Google Scholar 

  10. James TN. The delivery and distribution of coronary collateral circulation. Chest 1970; 58: 183–203.

    Google Scholar 

  11. James TN, Terasaki F, Pavlovich ER, Vikhert AM. Apoptosis and pleomorphic micromitochondriosis in the sinus nodes surgically excised from five patients with the long QT syndrome. J Lab Clin Med 1993; 122: 309–323.

    Google Scholar 

  12. James TN. Normal and abnormal consequences of apoptosis in the human heart: from postnatal morphogenesis to paroxysmal arrhythmias. Circulation 1994; 90: 556–573.

    Google Scholar 

  13. James TN, St. Martin E, Willis III PW, Lohr TO. Apoptosis as a possible cause of gradual development of complete heart block and fatal arrhythmias associated with absence of the AV node, the sinus node and the internodal pathways. Circulation 1996; 93: 1424–1438.

    Google Scholar 

  14. James TN, Nichols MM, Sapire DW, DiPatre PL, Lopez SM. Complete heart block and fatal right ventricular failure in an infant. Circulation 1996; 93: 1588–1600.

    Google Scholar 

  15. James TN. Long reflections on the QT interval. The Sixth Annual Gordon K. Moe Lecture. J Cardiovas Electrophysiol 1996; 7: 738–759.

    Google Scholar 

  16. James TN. Anatomy of the human sinus node. Anat Rec 1961; 141: 109–139.

    Google Scholar 

  17. James TN. The connecting pathways between the sinus node and AV node and between the right and left atrium in the human heart. Am Heart J 1963; 66: 498–508.

    Google Scholar 

  18. James TN. Morphology of the human atrioventricular node, with remarks pertinent to its electrophysiology. Am Heart J 1961; 62: 756–771.

    Google Scholar 

  19. James TN. Structure and function of the AV junction. The Mikamo Lecture for 1982. Jpn Circ J 1983; 47: 1–47.

    Google Scholar 

  20. James TN. A cardiogenic hypertensive chemoreflex. Anesth Analges 1989; 69: 633–646.

    Google Scholar 

  21. Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 1992; 119: 493–501.

    Google Scholar 

  22. Frink RJ, James TN. Normal blood supply to the human His bundle and proximal bundle branches. Circulation 1973; 47: 8–18.

    Google Scholar 

  23. Willerson JT, Campbell WB, Winniford MD, et al. Conversion from chronic to acute coronary artery disease: speculation regarding mechanisms. Am J Cardiol 1984; 54: 1349–1354.

    Google Scholar 

  24. Iwakura K, Ito H, Takiuchi S, et al. Alternation in the coronary blood flow velocity pattern in patients with no reflow and reperfused acute myocardial infarction. Circulation 1996; 94: 1269–1275.

    Google Scholar 

  25. Anversa P, Kajstura J, Reiss K, et al. Ischemic cardiomyopathy: myocyte cell loss, myocyte cellular hypertrophy, and myocyte cellular hyperplasia. Ann NY Acad Sci 1995; 752: 47–64.

    Google Scholar 

  26. Haider AW, Andreotti F, Thompson GR, Kluft C, Maseri A, Davies GJ. Serum lipoprotein(a) level is related to thrombin generation and spontaneous intermittent coronary occlusion in patients with acute myocardial infarction. Circulation 1996; 94: 2072–2076.

    Google Scholar 

  27. Nishizawa J, Nakai A, Higashi T, et al. Reperfusion causes significant activation of heat shock transcription factor 1 in ischemic rat heart. Circulation 1996; 94: 2185–2192.

    Google Scholar 

  28. Tank X-L, Qiu Y, Park S-W, Sun J-Z, Kalya A, Bolli R. Time course of late preconditioning against myocardial stunning in conscious pigs. Circ Res 1996; 79: 424–434.

    Google Scholar 

  29. Brooks G, Hearse DJ. Role of protein kinase C in ischemic preconditioning: player or spectator? Circ Res 1996; 79: 627–630.

    Google Scholar 

  30. Ovize M, Kloner RA, Przyklenk K. Stretch preconditions canine myocardium. Am J Physiol 1994; 266: H137–H146.

    Google Scholar 

  31. Gho BCG, Schoemaker RG, van den Doel MA, Duncker DJ, Verdouw PD. Myocardial protection by brief ischemia in noncardiac tissue. Circulation 1996; 94: 2193–2200.

    Google Scholar 

  32. Hoffman BF, Guo S-D, Feinmark SJ. Arrhythmias caused by platelet activating factor. J Cardiovas Electrophysiol 1996; 7: 120–133.

    Google Scholar 

  33. Evangelista V, Manarini S, Rotondo S, et al. Platelet/polymorphonuclear leukocyte interaction in dynamic conditions: evidence of adhesion cascade and cross talk between P-selectin and the β2 integrin CD11b/CD18. Blood 1996; 88: 4183–4194.

    Google Scholar 

  34. Burch GE, Meyers R, Abildskov JA. A new electro-cardiographic pattern observed in cerebrovascular accidents. Circulation 1954; 9: 719–723.

    Google Scholar 

  35. Yanowitz F, Preston B, Abildskov JA. Functional distribution of right and left stellate innervation to the ventricles: production of neurogenic electrocardiographic changes by unilateral alteration of sympathetic tone. Circ Res 1966; 18: 416–428.

    Google Scholar 

  36. Abildskov JA, Millar K, Burgess MJ, Vincent W. The electro-cardiogram and the central nervous system. Prog Cardiovasc Dis 1970; 13: 210–216.

    Google Scholar 

  37. Abildskov JA. The sympathetic imbalance hypothesis of QT interval prolongation. J Cardiovasc Electrophysiol 1991; 2: 355–359.

    Google Scholar 

  38. James TN. De Subitaneis Mortibus. XXVIII. Apoplexy of the heart. Circulation 1978; 57: 385–391.

    Google Scholar 

  39. Eckstein RW, Shintani F, Rowen Jr HE, Shimomura K, Ohya N. Identification of left coronary blood supply of aortic bodies in anesthetized dogs. J Appl Physiol 1971; 30: 488–492.

    Google Scholar 

  40. James TN, Isobe JH, Urthaler F. Analysis of components in a cardiogenic hypertensive chemoreflex. Circulation 1975; 52: 179–192.

    Google Scholar 

  41. Costa JL, Reese TS, Murphy DL. Serotonin storage in platelets: estimation of storage packet size. Science 1974; 183: 537–538.

    Google Scholar 

  42. Hayashi T, James TN, Buckingham DC. Ultrastructure and immunohistochemistry of the coronary chemoreceptor in human and canine hearts. Am Heart J 1995; 129: 946–959.

    Google Scholar 

  43. Dye LE, Urthaler F, MacLean WAH, Russell RO, Rackley CE, James TN. New arterial hypertension during myocardial infarction. South Med J 1978; 71: 289–292.

    Google Scholar 

  44. Robertson D, Hollister AS, Forman MB, Robertson RM. Reflexes unique to myocardial ischemia and infarction. J Am Coll Cardiol 1985; 5: 99B–104B.

    Google Scholar 

  45. Haerem JW. Sudden unexpected coronary death. The occurrence of platelet aggregates in the epicardial and myocardial vessels of man. Acta Pathol Microbiol Immunol Scand 1978; 86: 1–47.

    Google Scholar 

  46. Davies MJ, Thomas AC, Knapman PA, Hangartner JR. Intramyocardial platelet aggregation in patients with unstable angina suffering sudden ischemic cardiac death. Circulation 1986; 73: 418–427.

    Google Scholar 

  47. James TN. De Subitaneis Mortibus. XIX. On the cause of sudden death in pheochromocytoma, with special reference to the pulmonary arteries, the cardiac conduction system, and the aggregation of platelets. Circulation 1976; 54: 348–356.

    Google Scholar 

  48. Comroe Jr JH. The location and function of the chemoreceptors of the aorta. Am J Physiol 1939; 127: 176–191.

    Google Scholar 

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James, T.N., Alperin, J.B. Apoptotic myocardial degeneration in thrombotic thrombocytopenic purpura. Apoptosis 2, 384–394 (1997). https://doi.org/10.1023/A:1026457724661

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