Detection of abnormal cardiac adrenergic neuron activity in adriamycin-induced cardiomyopathy with iodine-125-metaiodobenzylguanidine.
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 less than 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 less than 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 less than 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.
Wakasugi
S
S
Division of Cardiology, Pathology and Nuclear Medicine, Center for Adult Diseases, Osaka, Japan.
Wada
A
A
Hasegawa
Y
Y
Nakano
S
S
Shibata
N
N
D019797:3-Iodobenzylguanidine; D000320:Adrenergic Fibers / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000009:adverse effects*; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D006333:Heart Failure / Q000139:chemically induced*; D006352:Heart Ventricles / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000378:metabolism*; D007462:Iodobenzenes / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013794:Thallium Radioisotopes / Q000378:metabolism
D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D013794:Thallium Radioisotopes; D019797:3-Iodobenzylguanidine; D004317:Doxorubicin; D009638:Norepinephrine