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

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.

Assessment of early left ventricular remodeling in orthotopic heart transplant recipients with cine magnetic resonance imaging: potential mechanisms.

We performed short axis cine magnetic resonance imaging studies in 11 patients 2 months after they underwent orthotopic heart transplantation (OHT), and in 10 control subjects, to measure left ventricular (LV) volumes, mass, and end-systolic wall stress to assess ventricular remodeling after OHT. Although there were no significant differences in ventricular volumes and ejection fractions between heart transplant recipients and control subjects, heart transplant recipients had significantly higher LV mass (198 +/- 61 vs 132 +/- 27 gm, p = 0.001). As a consequence of myocardial hypertrophy, end-systolic wall stress was significantly reduced in heart transplant recipients compared with control subjects (34 +/- 16 vs 57 +/- 10 kdyne/cm2, p = 0.001). Moreover, heart transplant recipients had significantly reduced end-systolic wall stress/volume ratio when compared with control subjects (0.89 +/- 0.3 vs 1.26 +/- 0.3 kdyne/cm2/ml, p < 0.01), indicating an already reduced LV contractility 2 months after heart transplantation. Univariate regression analysis revealed a significant correlation between LV mass and averaged cyclosporine levels, but no correlation between LV mass and blood pressure, cold ischemic time, acute rejection, age, body mass, blood pressure, plasma catecholamine levels, or plasma renin activity. Magnetic resonance imaging demonstrates early LV remodeling after OHT with reduced myocardial contractility. Cyclosporine may be contributing to these changes.

Measurement of fibroblast proliferative activity in bronchoalveolar lavage fluid in the analysis of obliterative bronchiolitis among lung transplant recipients.

BACKGROUND: Bronchiolitis obliterans occurs in 30% to 80% of lung-transplant recipients and is a direct cause of death in more than 40% of patients with this complication. This study assessed the potential utility of measuring fibroblast-proliferative activity in bronchoalveolar lavage fluid from lung-transplant recipients to better understand the pathogenesis of this process. METHODS: The capacity of bronchoalveolar lavage fluid obtained from transplant recipients, during routine surveillance bronchoscopy, to stimulate the proliferation of human lung fibroblasts in vitro was assessed retrospectively and compared to that of control subjects. For each recipient, a correlation was made between the fibroblast-proliferative activity in serial lavage samples over time and the other modalities employed for detecting post-transplant complications including spirometry, transbronchial lung biopsy, and high-resolution computed tomography. RESULTS: There was a significant difference in fibroblast-proliferative activity between volunteer and transplant recipient groups (p = 0.002). Further, for each transplant recipient, the decline in the forced expired flow rate between 25% and 75% of expired volume (FEF(25%-75%)) was correlated with the mean fibroblast-proliferative activity during the period of this study (r = 0.83; p = 0.04). CONCLUSIONS: A sustained increase in fibroblast-proliferative activity in lavage supernatant precedes both histologic and physiologic evidence of bronchiolitis obliterans. Relative to an increase in fibroblast-proliferative activity or abnormalities in FEF25%-75%, a decrease in forced expiratory volume in 1 second is a late finding.