2006 Heart-Brain summit proceedings

Heart transplantation:
A magnified model of heart-brain interactions

Mohamad H. Yamani, MD

Section of Heart Failure and Cardiac Transplant Medicine
Department of Cardiovascular Medicine
Cleveland Clinic
Cleveland, OH

Randall C. Starling, MD, MPH

Section of Heart Failure and Cardiac Transplant Medicine
Department of Cardiovascular Medicine
Cleveland Clinic
Cleveland, OH

ARTICLE INTRODUCTION

The heart-brain interaction is a burgeoning area of science that has been gaining visibility among researchers interested in the relationship between the central nervous system and cardiovascular system. This review explores heart transplantation as a model for providing insight into the heart-brain link, with an emphasis on findings from recent human investigations.

CITATIONS

  1. Taylor DO, Edwards LB, Boucek MM, et al.
    Registry of the International Society for Heart and Lung Transplantation: twentysecond official adult heart transplant report—2005. J Heart Lung Transplant 2005; 24:945–955.
    http://www.ncbi.nlm.nih.gov/pubmed/16102427

  2. Yamani MH, Lauer MS, Starling RC, et al.
    Impact of donor spontaneous intracranial hemorrhage on outcome following heart transplantation. Am J Transplant 2004; 4:257–261.
    http://www.ncbi.nlm.nih.gov/pubmed/14974948
  3. Tsai FC, Marelli D, Bresson J, et al.
    Use of hearts transplanted from donors with atraumatic intracranial bleeds. J Heart Lung Transplant 2002; 21:623.
    http://www.ncbi.nlm.nih.gov/pubmed/12057694
  4. Mehra MR, Uber PA, Ventura HO, Scott RL, Park MH.
    The impact of mode of donor brain death on cardiac allograft vasculopathy: an intravascular ultrasound study. J Am Coll Cardiol 2004; 43:806–810.
    http://www.ncbi.nlm.nih.gov/pubmed/14998621
  5. Yamani MH, Erinc K, Starling RC, et al.
    Donor intracranial bleeding is associated with advanced transplant coronary vasculopathy: evidence from intravascular ultrasound. Transplant Proc 2004; 36:2564–2566.
    http://www.ncbi.nlm.nih.gov/pubmed/15621090
  6. Novitzky D, Wicomb WN, Cooper DK, Barnard CN.
    Electrocardiographic, haemodynamic, and endocrine changes occuring during experimental brain death in the Chacma baboon. Heart Transplant 1984; 3:193.
  7. Darracott-Cankovic S, Stovin PG, Wheeldon D, Wallwork J, Wells F, English TA.
    Effect of donor heart damage on survival after transplantation. Eur J Cardiothorac Surg 1989; 3:525–532.
    http://www.ncbi.nlm.nih.gov/pubmed/2635940
  8. Baroldi G, Di Pasquale G, Silver MD, Pinelli G, Lusa AM, Fineschi V.
    Type and extent of myocardial injury related to brain damage and its significance in heart transplantation: a morphometric study. J Heart Lung Transplant 1997; 16:994–1000.
    http://www.ncbi.nlm.nih.gov/pubmed/9361241
  9. Shanlin RJ, Sole MJ, Rahimifar M, Tator CH, Factor SM.
    Increased intracranial pressure elicits hypertension, increased sympathetic activity, electrocardiographic abnormalities and myocardial damage in rats. J Am Coll Cardiol 1988; 12:727–736.
    http://www.ncbi.nlm.nih.gov/pubmed/3403832
  10. White M, Wiechmann RJ, Roden RL, et al.
    Cardiac beta-adrenergic neuroeffector systems in acute myocardial dysfunction related to brain injury. Evidence for catecholamine-mediated myocardial damage. Circulation 1995; 92:2183–2189.
    http://www.ncbi.nlm.nih.gov/pubmed/7554200
  11. Shivalkar B, Van Loon J, Wieland W, et al.
    Variable effects of explosive or gradual increase of intracranial pressure on myocardial structure and function. Circulation 1993; 87:230–239.
    http://www.ncbi.nlm.nih.gov/pubmed/8419012
  12. Hynes RO.
    Integrins: a family of cell surface receptors. Cell 1987; 48:549–554.
    http://www.ncbi.nlm.nih.gov/pubmed/3028640
  13. Yamani MH, Masri S, Ratliff NB, et al.
    The role of vitronectin receptor (_v_3) and tissue factor in the pathogenesis of transplant vasculopathy. J Am Coll Cardiol 2002; 39:804–810.
    http://www.ncbi.nlm.nih.gov/pubmed/11869845
  14. Horton MA.
    The alpha v beta 3 integrin “vitronectin receptor.” Int J Biochem and Cell Biol 1997; 29:721–725.
    http://www.ncbi.nlm.nih.gov/pubmed/9251239
  15. Byzova T, Plow E.
    Activation of _v_3 on vascular cells controls recognition of prothrombin. J Cell Biol 1998; 143:2081–2092.
    http://www.ncbi.nlm.nih.gov/pubmed/9864377
  16. Byzova T, Rabbani R, D’Souza SE, Plow EF.
    Role of integrin _v_3 in vascular biology. Thromb Haemost 1998; 80:726–734.
    http://www.ncbi.nlm.nih.gov/pubmed/9843163
  17. Hermann P, Armant M, Brown E, et al.
    The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23. J Cell Biol 1999; 144:767–775.
    http://www.ncbi.nlm.nih.gov/pubmed/10037797
  18. Clark EA, Brugge JS.
    Integrins and signal transduction pathways: the road taken. Science 1995; 268:233–239.
    http://www.ncbi.nlm.nih.gov/pubmed/7716514
  19. Stromblad S, Cheresh DA.
    Integrins, angiogenesis and vascular cell survival. Chem Biol 1996; 3:881–885.
    http://www.ncbi.nlm.nih.gov/pubmed/8939711
  20. Yamani MH, Cook DJ, Tuzcu EM, et al.
    Systemic activation of integrin alphaVbeta3 in donors with spontaneous intracerebral hemorrhage is associated with subsequent development of vasculopathy in the heart transplant recipient. J Heart Lung Transplant 2005; 24:1014–1018.
    http://www.ncbi.nlm.nih.gov/pubmed/16102435
  21. Bader BL, Rayburn H, Crowley D, et al.
    Extensive vasculogenesis, angiogenesis, and organogenesis precede lethality in mice lacking all alpha v integrins. Cell 1998; 95:507–519.
    http://www.ncbi.nlm.nih.gov/pubmed/9827803
  22. Yamani MH, Haji SA, Starling RC, et al.
    Myocardial ischemic-fibrotic injury following human heart transplantation is associated with increased progression of vasculopathy, decreased cellular rejection, and poor long-term outcome. J Am Coll Cardiol 2002; 39:970–977.
    http://www.ncbi.nlm.nih.gov/pubmed/11897438
  23. Yamani MH, Tuzcu EM, Starling RC, et al.
    Myocardial ischemic injury after heart transplantation is associated with upregulation of vitronectin receptor (_v_3), activation of the matrix metalloproteinase induction system, and subsequent development of coronary vasculopathy. Circulation 2002; 105:1955–1961.
    http://www.ncbi.nlm.nih.gov/pubmed/11997283
  24. Yamani MH, Starling RC, Cook DJ, et al.
    Donor spontaneous intracerebral hemorrhage is associated with systemic activation of MMP-2 and MMP-9 and subsequent development of coronary vasculopathy in the heart transplant recipient. Circulation 2003; 108:1724–1728.
    http://www.ncbi.nlm.nih.gov/pubmed/12975253
  25. Romanic AM, White RF, Arleth AJ, et al.
    Matrix metalloproteinase expression increases after cerebral focal ischemia in rats: inhibition of matrix metalloproteinase-9 reduces infarct size. Stroke 1998; 29:1020–1030.
    http://www.ncbi.nlm.nih.gov/pubmed/9596253
  26. Lapchak PA, Chapman DF, Zifin JA.
    Metalloproteinase inhibition reduces thrombolytic (tissue plasminogen activator)-induced hemorrhage after thrombolytic stroke. Stroke 2000; 31:3034–3040.
    http://www.ncbi.nlm.nih.gov/pubmed/11108768
  27. Khan KM, Falcone DJ, Kraemer R.
    Nerve growth factor activation of Erk-1 and Erk-2 induces matrix metalloproteinase-9 expression in vascular smooth muscle cells. J Biol Chem 2002; 277:2353–2359.
    http://www.ncbi.nlm.nih.gov/pubmed/11698409
  28. Xu Y, Kumar D, Dyck J, et al.
    AT1 and AT2 receptor expression and blockade after acute ischemia-reperfusion in isolated working rat hearts. Am J Physiol Heart Circ Physiol 2002; 282:H1206–H1215.
    http://www.ncbi.nlm.nih.gov/pubmed/11893553
  29. Gianello P, Fishbein J, Besse T, et al.
    Measurement of the vasoconstrictive substances endothelin, angiotensin II, and thromboxane B2 in cold storage solution can reveal ischemic insults. Transpl Int 1994; 7:11–16.
    http://www.ncbi.nlm.nih.gov/pubmed/8117396
  30. Klahr S, Morrissey J.
    Angiotensin II and gene expression in kidney. Am J Kidney Dis 1998; 31:171–176.
    http://www.ncbi.nlm.nih.gov/pubmed/9428470
  31. Nataraj C, Oliverio M, Mannon R, et al.
    Angiotensin II regulates cellular immune response through a calcineurin-dependent pathway. J Clin Invest 1999; 104:1693–1701.
    http://www.ncbi.nlm.nih.gov/pubmed/10606623
  32. Yoshida J, Yamamoto K, Mano T, et al.
    Angiotensin II type 1 and endothelin type A receptor antagonists modulate the extracellular matrix regulatory system differently in diastolic heart failure. J Hypertens 2003; 21:437–444.
    http://www.ncbi.nlm.nih.gov/pubmed/12569276
  33. Masutomo K, Makino N, Fushiki MS, et al.
    Effects of losartan on the collagen degradative enzymes in hypertrophic and congestive types of cardiomyopathic hamsters. Mol Cell Biochem 2001; 224:19–27.
    http://www.ncbi.nlm.nih.gov/pubmed/11693196
  34. Niel-Dwyer G, Cruickshank JM.
    Plasma renin and angiotensin II levels in subarachnoid hemorrhage. J Neurol Sci 1974; 23:463–471.
    http://www.ncbi.nlm.nih.gov/pubmed/4372326
  35. Fassot C, Lambert G, Gaudet-Lambert E, Friberg P, Elghozi JL.
    Beneficial effect of renin-angiotensin system for maintaining blood pressure control following subarachnoid haemorrhage. Brain Res Bull 1999; 50:127–132.
    http://www.ncbi.nlm.nih.gov/pubmed/10535331
  36. Fassot C, Lambert G, Elghozi JL, Lambert E.
    Impact of the reninangiotensin system on cerebral perfusion following subarachnoid haemorrahge in the rat. J Physiol 2001; 535:533–540.
    http://www.ncbi.nlm.nih.gov/pubmed/11533142
  37. Yamani MH, Cook DJ, Tuzcu EM, et al.
    Systemic upregulation of angiotensin II type 1 receptor in cardiac donors with spontaneous intracerebral hemorrhage. Am J Transplant 2004; 4:1097–1102.
    http://www.ncbi.nlm.nih.gov/pubmed/15196067
  38. Eisen HJ, Tuzcu EM, Dorent R, et al.
    Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med 2003; 349:847–858.
    http://www.ncbi.nlm.nih.gov/pubmed/12944570