Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1991 May;87(5):1681–1690. doi: 10.1172/JCI115185

Evidence for regional catecholamine uptake and storage sites in the transplanted human heart by positron emission tomography.

M Schwaiger 1, G D Hutchins 1, V Kalff 1, K Rosenspire 1, M S Haka 1, S Mallette 1, G M Deeb 1, G D Abrams 1, D Wieland 1
PMCID: PMC295266  PMID: 2022739

Abstract

Positron emission tomography in combination with the newly introduced catecholamine analogue [11C]hydroxyephedrine ([11C]HED) enables the noninvasive delineation of sympathetic nerve terminals of the heart. To address the ongoing controversy over possible reinnervation of the human transplant, 5 healthy control subjects and 11 patients were studied after cardiac transplant by this imaging approach. Regional [11C]HED retention was compared to regional blood flow as assessed by rubidium-82. Transplant patients were divided into two groups. Group I had recent (less than 1 yr, 4.4 +/- 2.3 mo) surgery, while group II patients underwent cardiac transplantation more than 2 yr before imaging (3.5 +/- 1.3 yr). [11C]HED retention paralleled blood flow in normals, but was homogeneously reduced in group I. In contrast, group II patients revealed heterogeneous [11C]HED retention, with increased uptake in the proximal anterior and septal wall. Quantitative evaluation of [11C]HED retention revealed a 70% reduction in group I and 59% reduction in group II patients (P less than 0.001). In group II patients, [11C]HED retention reached 60% of normal in the proximal anterior wall. These data suggest the presence of neuronal tissue in the transplanted human heart, which may reflect regional sympathetic reinnervation.

Full text

PDF
1681

Images in this article

1683Image
on p.1683
1683Image
on p.1683
1684Image
on p.1684
1686Image
on p.1686
1687Image
on p.1687
1688Image
on p.1688
1689Image
on p.1689

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Banner N. R., Patel N., Cox A. P., Patton H. E., Lachno D. R., Yacoub M. H. Altered sympathoadrenal response to dynamic exercise in cardiac transplant recipients. Cardiovasc Res. 1989 Nov;23(11):965–972. doi: 10.1093/cvr/23.11.965. [DOI] [PubMed] [Google Scholar]
  2. Beck W., Barnard C. N., Schrire V. Heart rate after cardiac transplantation. Circulation. 1969 Oct;40(4):437–445. doi: 10.1161/01.cir.40.4.437. [DOI] [PubMed] [Google Scholar]
  3. Bristow M. R. The surgically denervated, transplanted human heart. Circulation. 1990 Aug;82(2):658–660. doi: 10.1161/01.cir.82.2.658. [DOI] [PubMed] [Google Scholar]
  4. DONALD D. E., SHEPHERD J. T. INITIAL CARDIOVASCULAR ADJUSTMENT TO EXERCISE IN DOGS WITH CHRONIC CARDIAC DENERVATION. Am J Physiol. 1964 Dec;207:1325–1329. doi: 10.1152/ajplegacy.1964.207.6.1325. [DOI] [PubMed] [Google Scholar]
  5. DONG E., Jr, HURLEY E. J., LOWER R. R., SHUMWAY N. E. PERFORMANCE OF THE HEART TWO YEARS AFTER AUTOTRANSPLANTATION. Surgery. 1964 Jul;56:270–274. [PubMed] [Google Scholar]
  6. Ebert P. A., Sabiston D. C., Jr Pharmacologic quantitation of cardiac sympathetic reinnervation. Surgery. 1970 Jul;68(1):123–127. [PubMed] [Google Scholar]
  7. Ewing D. J., Martyn C. N., Young R. J., Clarke B. F. The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care. 1985 Sep-Oct;8(5):491–498. doi: 10.2337/diacare.8.5.491. [DOI] [PubMed] [Google Scholar]
  8. Fragomeni L. S., Kaye M. P. The Registry of the International Society for Heart Transplantation: fifth official report--1988. J Heart Transplant. 1988 Jul-Aug;7(4):249–253. [PubMed] [Google Scholar]
  9. Fuller R. W., Snoddy H. D., Perry K. W., Bernstein J. R., Murphy P. J. Formation of alpha-methylnorepinephrine as a metabolite of metaraminol in guinea pigs. Biochem Pharmacol. 1981 Oct;30(20):2831–2836. doi: 10.1016/0006-2952(81)90422-6. [DOI] [PubMed] [Google Scholar]
  10. Glowniak J. V., Turner F. E., Gray L. L., Palac R. T., Lagunas-Solar M. C., Woodward W. R. Iodine-123 metaiodobenzylguanidine imaging of the heart in idiopathic congestive cardiomyopathy and cardiac transplants. J Nucl Med. 1989 Jul;30(7):1182–1191. [PubMed] [Google Scholar]
  11. Guyton R. A., Bianco J. A., Ostheimer G. W., Shanahan E. A., Daggett W. M. Adrenergic control of ventricular performance in normal and cardiac-denervated dogs. Am J Physiol. 1972 Nov;223(5):1021–1028. doi: 10.1152/ajplegacy.1972.223.5.1021. [DOI] [PubMed] [Google Scholar]
  12. Henderson E. B., Kahn J. K., Corbett J. R., Jansen D. E., Pippin J. J., Kulkarni P., Ugolini V., Akers M. S., Hansen C., Buja L. M. Abnormal I-123 metaiodobenzylguanidine myocardial washout and distribution may reflect myocardial adrenergic derangement in patients with congestive cardiomyopathy. Circulation. 1988 Nov;78(5 Pt 1):1192–1199. doi: 10.1161/01.cir.78.5.1192. [DOI] [PubMed] [Google Scholar]
  13. Kavanagh T., Yacoub M. H., Mertens D. J., Kennedy J., Campbell R. B., Sawyer P. Cardiorespiratory responses to exercise training after orthotopic cardiac transplantation. Circulation. 1988 Jan;77(1):162–171. doi: 10.1161/01.cir.77.1.162. [DOI] [PubMed] [Google Scholar]
  14. Kaye M. P., Wells D. J., Tyce G. M. Nerve growth factor-enhanced reinnervation of surgically denervated canine heart. Am J Physiol. 1979 Apr;236(4):H624–H628. doi: 10.1152/ajpheart.1979.236.4.H624. [DOI] [PubMed] [Google Scholar]
  15. Kontos H. A., Thames M. D., Lower R. R. Responses to electrical and reflex autonomic stimulation in dogs with cardiac transplantation before and after reinnervation. J Thorac Cardiovasc Surg. 1970 Mar;59(3):382–392. [PubMed] [Google Scholar]
  16. Mohanty P. K., Sowers J. R., Thames M. D., Beck F. W., Kawaguchi A., Lower R. R. Myocardial norepinephrine, epinephrine and dopamine concentrations after cardiac autotransplantation in dogs. J Am Coll Cardiol. 1986 Feb;7(2):419–424. doi: 10.1016/s0735-1097(86)80515-0. [DOI] [PubMed] [Google Scholar]
  17. Niset G. L., Piret A. A., Delbarre N., De Smet J. M., Joris M. P., Goldstein J. P., Le Clerc J. L., Primo G., Degré S. Evaluation fonctionnelle cardio-respiratoire non invasive un mois et un an après transplantation cardiaque orthotopique. Ann Cardiol Angeiol (Paris) 1988 Jan;37(1):9–12. [PubMed] [Google Scholar]
  18. Norvell J. E., Lower R. R. Degeneration and regeneration of the nerves of the heart after transplantation. Transplantation. 1973 Mar;15(3):337–344. doi: 10.1097/00007890-197303000-00015. [DOI] [PubMed] [Google Scholar]
  19. Pope S. E., Stinson E. B., Daughters G. T., 2nd, Schroeder J. S., Ingels N. B., Jr, Alderman E. L. Exercise response of the denervated heart in long-term cardiac transplant recipients. Am J Cardiol. 1980 Aug;46(2):213–218. doi: 10.1016/0002-9149(80)90060-0. [DOI] [PubMed] [Google Scholar]
  20. Regitz V., Bossaller C., Strasser R., Schüler S., Hetzer R., Fleck E. Myocardial catecholamine content after heart transplantation. Circulation. 1990 Aug;82(2):620–623. doi: 10.1161/01.cir.82.2.620. [DOI] [PubMed] [Google Scholar]
  21. Rosenspire K. C., Schwaiger M., Mangner T. J., Hutchins G. D., Sutorik A., Kuhl D. E. Metabolic fate of [13N]ammonia in human and canine blood. J Nucl Med. 1990 Feb;31(2):163–167. [PubMed] [Google Scholar]
  22. Rowan R. A., Billingham M. E. Myocardial innervation in long-term heart transplant survivors: a quantitative ultrastructural survey. J Heart Transplant. 1988 Nov-Dec;7(6):448–452. [PubMed] [Google Scholar]
  23. Schroeder J. S. Hemodynamic performance of the human transplanted heart. Transplant Proc. 1979 Mar;11(1):304–308. [PubMed] [Google Scholar]
  24. Schwaiger M., Kalff V., Rosenspire K., Haka M. S., Molina E., Hutchins G. D., Deeb M., Wolfe E., Jr, Wieland D. M. Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography. Circulation. 1990 Aug;82(2):457–464. doi: 10.1161/01.cir.82.2.457. [DOI] [PubMed] [Google Scholar]
  25. Seki S., Danielson G. K. Characteristics of cardiac reinnervation in growing calves. J Thorac Cardiovasc Surg. 1971 Oct;62(4):602–607. [PubMed] [Google Scholar]
  26. Sisson J. C., Wieland D. M. Radiolabeled meta-iodobenzylguanidine: pharmacology and clinical studies. Am J Physiol Imaging. 1986;1(2):96–103. [PubMed] [Google Scholar]
  27. Stevenson L. W., Sietsema K., Tillisch J. H., Lem V., Walden J., Kobashigawa J. A., Moriguchi J. Exercise capacity for survivors of cardiac transplantation or sustained medical therapy for stable heart failure. Circulation. 1990 Jan;81(1):78–85. doi: 10.1161/01.cir.81.1.78. [DOI] [PubMed] [Google Scholar]
  28. Vracko R., Thorning D., Frederickson R. G. Fate of nerve fibers in necrotic, healing, and healed rat myocardium. Lab Invest. 1990 Oct;63(4):490–501. [PubMed] [Google Scholar]
  29. WILLMAN V. L., COOPER T., HANLON C. R. RETURN OF NEURAL RESPONSES AFTER AUTOTRANSPLANTATION OF THE HEART. Am J Physiol. 1964 Jul;207:187–189. doi: 10.1152/ajplegacy.1964.207.1.187. [DOI] [PubMed] [Google Scholar]
  30. Wieland D. M., Rosenspire K. C., Hutchins G. D., Van Dort M., Rothley J. M., Mislankar S. G., Lee H. T., Massin C. C., Gildersleeve D. L., Sherman P. S. Neuronal mapping of the heart with 6-[18F]fluorometaraminol. J Med Chem. 1990 Mar;33(3):956–964. doi: 10.1021/jm00165a012. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES