Iodine-123 metaiodobenzylguanidine scintigraphic assessment of the transplanted human heart: evidence for late reinnervation

Department of Medicine, University of California at San Francisco.

OBJECTIVES. This study attempted to determine whether cardiac sympathetic reinnervation occurs late after orthotopic heart transplantation. BACKGROUND. Metaiodobenzylguanidine (MIBG) is taken up by myocardial sympathetic nerves. Iodine-123 (I-123) MIBG cardiac uptake reflects intact myocardial sympathetic innervation of the heart. Cardiac transplant recipients do not demonstrate I-123 MIBG cardiac uptake when studied < 6 months from transplantation. However, physiologic and biochemical studies suggest that sympathetic reinnervation of the heart can occur > 1 year after transplantation. METHODS. We performed serial cardiac I-123 MIBG imaging in 23 cardiac transplant recipients early (< or = 1 year) and late (> 1 year) after operation. In 16 subjects transmyocardial norepinephrine release was measured late after transplantation. RESULTS. No subject had visible I-123 MIBG uptake on imaging < 1 year after transplantation. However, 11 (48%) of 23 subjects developed visible cardiac I-123 MIBG uptake 1 to 2 years after transplantation. Only 3 (25%) of 12 subjects with a pretransplantation diagnosis of idiopathic cardiomyopathy demonstrated I-123 MIBG uptake compared with 8 (73%) of 11 with a pretransplantation diagnosis of ischemic or rheumatic heart disease (p = 0.04). All 10 subjects with a net myocardial release of norepinephrine had cardiac I-123 MIBG uptake; all 6 subjects without a net release of norepinephrine had no cardiac I-123 MIBG uptake. CONCLUSIONS. Sympathetic reinnervation of the transplanted human heart can occur > 1 year after operation, as assessed by I-123 MIBG imaging and the transmyocardial release of norepinephrine. Reinnervation is less likely to occur in patients with a pretransplantation diagnosis of idiopathic cardiomyopathy than in those with other etiologies of congestive heart failure.

This article has been cited by other articles:

				N. M. Banki, A. Kopelnik, M. W. Dae, J. Miss, P. Tung, M. T. Lawton, B. J. Drew, E. Foster, W. Smith, W. W. Parmley, et al. Acute Neurocardiogenic Injury After Subarachnoid Hemorrhage Circulation, November 22, 2005; 112(21): 3314 - 3319. [Abstract] [Full Text] [PDF]

				M. Mabuchi, M. Imamura, N. Kubo, K. Morita, K. Noriyasu, T. Tsukamoto, K. Yasuda, and N. Tamaki Sympathetic Denervation and Reinnervation After the Maze Procedure J. Nucl. Med., July 1, 2005; 46(7): 1089 - 1094. [Abstract] [Full Text] [PDF]

				F. M. Bengel, P. Ueberfuhr, J. Karja, K. Schreiber, S. G. Nekolla, B. Reichart, and M. Schwaiger Sympathetic reinnervation, exercise performance and effects of {beta}-adrenergic blockade in cardiac transplant recipients Eur. Heart J., October 1, 2004; 25(19): 1726 - 1733. [Abstract] [Full Text] [PDF]

				S. S. Lovric, V. Avbelj, R. Trobec, D. Zorman, P. Rakovec, S. Hojker, B. Gersak, and M. Milcinski Sympathetic reinnervation after heart transplantation, assessed by iodine-123 metaiodobenzylguanidine imaging, and heart rate variability Eur. J. Cardiothorac. Surg., October 1, 2004; 26(4): 736 - 741. [Abstract] [Full Text] [PDF]

				F. M. Bengel, P. Ueberfuhr, T. Hesse, N. Schiepel, S. I. Ziegler, S. Scholz, S. G. Nekolla, B. Reichart, and M. Schwaiger Clinical Determinants of Ventricular Sympathetic Reinnervation After Orthotopic Heart Transplantation Circulation, August 13, 2002; 106(7): 831 - 835. [Abstract] [Full Text] [PDF]

				F. M. Bengel, P. Ueberfuhr, N. Schiepel, S. G. Nekolla, B. Reichart, and M. Schwaiger Effect of Sympathetic Reinnervation on Cardiac Performance after Heart Transplantation N. Engl. J. Med., September 6, 2001; 345(10): 731 - 738. [Abstract] [Full Text] [PDF]

				S. Hunt Reinnervation of the Transplanted Heart -- Why Is It Important? N. Engl. J. Med., September 6, 2001; 345(10): 762 - 764. [Full Text] [PDF]

				K. Odaka, W. von Scheidt, S. I. Ziegler, P. Ueberfuhr, S. G. Nekolla, B. Reichart, F. M. Bengel, and M. Schwaiger Reappearance of Cardiac Presynaptic Sympathetic Nerve Terminals in the Transplanted Heart: Correlation Between PET Using 11C-Hydroxyephedrine and Invasively Measured Norepinephrine Release J. Nucl. Med., July 1, 2001; 42(7): 1011 - 1016. [Abstract] [Full Text] [PDF]

				I. Carrio Cardiac Neurotransmission Imaging J. Nucl. Med., July 1, 2001; 42(7): 1062 - 1076. [Abstract] [Full Text] [PDF]

				P. Salmon, S. C. Stanford, G. Mikhail, S. Zielinski, and J. R. Pepper Hemodynamic and Emotional Responses to a Psychological Stressor After Cardiac Transplantation Psychosom Med, March 1, 2001; 63(2): 289 - 299. [Abstract] [Full Text] [PDF]

				D. A. Murphy, G. W. Thompson, J. L. Ardell, R. McCraty, R. S. Stevenson, V. E. Sangalang, R. Cardinal, M. Wilkinson, S. Craig, F. M. Smith, et al. The heart reinnervates after transplantation Ann. Thorac. Surg., June 1, 2000; 69(6): 1769 - 1781. [Abstract] [Full Text] [PDF]

				P. Uberfuhr, S. Ziegler, M. Schwaiblmair, B. Reichart, and M. Schwaiger Incomplete sympathic reinnervation of the orthotopically transplanted human heart: Observation up to 13 years after heart transplantation Eur. J. Cardiothorac. Surg., February 1, 2000; 17(2): 161 - 168. [Abstract] [Full Text] [PDF]

				N. Hogan, B. Casadei, and D. J. Paterson Nitric oxide donors can increase heart rate independent of autonomic activation J Appl Physiol, July 1, 1999; 87(1): 97 - 103. [Abstract] [Full Text] [PDF]

				F. M. Bengel, P. Ueberfuhr, S. I. Ziegler, S. Nekolla, B. Reichart, and M. Schwaiger Serial Assessment of Sympathetic Reinnervation After Orthotopic Heart Transplantation : A Longitudinal Study Using PET and C-11 Hydroxyephedrine Circulation, April 13, 1999; 99(14): 1866 - 1871. [Abstract] [Full Text] [PDF]

				G. Kojda and K. Kottenberg Regulation of basal myocardial function by NO Cardiovasc Res, March 1, 1999; 41(3): 514 - 523. [Full Text] [PDF]

				C. Kondo, M. Nakazawa, K. Momma, and K. Kusakabe Sympathetic Denervation and Reinnervation After Arterial Switch Operation for Complete Transposition Circulation, June 23, 1998; 97(24): 2414 - 2419. [Abstract] [Full Text] [PDF]

				L. Bernardi, C. Valenti, J. Wdowczyck-Szulc, A. W. Frey, M. Rinaldi, G. Spadacini, C. Passino, L. Martinelli, M. Vigano, and G. Finardi Influence of Type of Surgery on the Occurrence of Parasympathetic Reinnervation After Cardiac Transplantation Circulation, April 14, 1998; 97(14): 1368 - 1374. [Abstract] [Full Text] [PDF]

				P. Musialek, M. Lei, H. F. Brown, D. J. Paterson, and B. Casadei Nitric Oxide Can Increase Heart Rate by Stimulating the Hyperpolarization-Activated Inward Current, If Circ. Res., July 19, 1997; 81(1): 60 - 68. [Abstract] [Full Text]

				M. M. Givertz, L. H. Hartley, and W. S. Colucci Long-term Sequential Changes in Exercise Capacity and Chronotropic Responsiveness After Cardiac Transplantation Circulation, July 1, 1997; 96(1): 232 - 237. [Abstract] [Full Text]

				S. Singh, P. I. Johnson, R. E. Lee, E. Orfei, V. A. Lonchyna, H. J. Sullivan, A. Montoya, H. Tran, W. H. Wehrmacher, and R. D. Wurster TOPOGRAPHY OF CARDIAC GANGLIA IN THE ADULT HUMAN HEART J. Thorac. Cardiovasc. Surg., October 1, 1996; 112(4): 943 - 953. [Abstract] [Full Text]

				E. Toledo, I. Pinhas, D. Aravot, Y. Almog, and S. Akselrod Functional restitution of cardiac control in heart transplant patients Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2002; 282(3): R900 - R908. [Abstract] [Full Text] [PDF]