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Detection of Abnormal Cardiac Adrenergic Neuron Activity in Adriamycin-Induced Cardiomyopathy with Iodine-125-Metaiodobenzylguanidine

Division of Cardiology, Pathology and Nuclear Medicine, The Center for Adult Diseases, Osaka, Japan

Correspondence: For reprints contact: Shigetoshi Wakasugi, MD, Dept. of Nuclear Medicine, Massachusetts General Hospital, Boston, MA 02114.

ABSTRACT

Radiolabeled metaiodobenzylguanidine (MIBG), an analog of norepinephrine (NE), serves as an index of adrenergic neuron integrity and function. Using a rat model of adriamycin-induced cardiomyopathy, we tested the hypothesis that abnormal cardiac adrenergic neuron activity may appear and be exacerbated dose-dependently in adriamycin cardiomyopathy. The degree of vacuolar degeneration of myocardial cells was analyzed in relation to the duration of adriamycin treatment (2 mg/kg, once a week). There were no abnormalities or only isolated degeneration in the 1- or 2-wk treatment groups, isolated or scattered degeneration in half of the 3-wk group, frequent scattered degeneration in the 4-wk group, scattered or focal degeneration in the 5-wk group, and extensive degeneration in the 8-wk group. Myocardial accumulation of [¹²⁵I]MIBG 4 hr after intravenous injection did not differ between the controls and the groups treated 3 wk or less. However, the 4-wk group had a slightly lower accumulation in the right ventricular wall (82% of the control) and significantly lower accumulation in the left ventricular wall (about 66% of the control: p < 0.05). In the 5-wk group, MIBG accumulation in the right and left ventricular wall was 35% and 27% of that in controls, respectively (p < 0.001). In the 8-wk group, MIBG accumulation in the right and left ventricular wall was 18% and 14% of that in controls, respectively (p < 0.001). Thus, MIBG accumulation in the myocardium decreased in an adriamycin dose-dependent manner. The appearance of impaired cardiac adrenergic neuron activity in the presence of slight myocardial impairment (scattered or focal vacuolar degeneration) indicates that MIBG scintigraphy may be a useful method for detection of adriamycin-induced cardiomyopathy.

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