Sympathetic nerve alterations assessed with I-123-MIBG in the failing human heart

Norepinephrine (NE) reuptake function is impaired in heart failure and this may participate in myocyte hyperstimulation by the neurotransmitter. This alteration can be assessed by I-123-metaiodobenzylguanidine (MIBG) scintigr aphy. Methods: To determine whether the impairment of neuronal NE reuptake was reversible after metoprolol therapy, we studied 18 patients (43 +/- 7 y ) with idiopathic dilated cardiomyopathy who were stabilized at least for 3 mo with captopril and diuretics. Patients underwent, before and after 6 mo of therapy with metoprolol, measurements of radionuclide left ventricular ejection fraction (LVEF), maximal oxygen consumption and plasma NE concentr ation. The cardiac adrenergic innervation function was scintigraphically as sessed with MIBG uptake and release measurements on the planar images obtai ned 20 min and 4 h after tracer injection. To evaluate whether metoprolol h ad a direct interaction with cardiac MIBG uptake and release, six normal su bjects were studied before and after a 1-mo metoprolol intake. Results: In controls, neither cardiac MIBG uptake and release nor circulating NE concen tration changed after the 1-mo metoprolol intake. Conversely, after a 6-mo therapy with metoprolol, patients showed increased cardiac MIBG uptake (129 % +/- 10% versus 138% +/- 17%; P = 0.009), unchanged cardiac MIBG release a nd decreased plasma NE concentration (0.930 +/- 412 versus 0.721 +/- 0.370 ng/mL; P = 0.02). In parallel, patients showed improved New York Heart Asso ciation class (2.44 +/- 0.51 versus 2.05 +/- 0.23; P = 0.004) and increased LVEF (20% +/- 8% versus 27% +/- 8%; P = 0.0005), whereas maximal oxygen up take remained unchanged. Conclusion: Thus, a parallel improvement of myocar dial NE reuptake and of hemodynamics was observed after a 6-mo metoprolol t herapy, suggesting that such agents may be beneficial in heart failure by d irectly protecting the myocardium against excessive NE stimulation.