Assessment of adrenergic neuron function altered with progression of heart failure.
We used MIBG to evaluate cardiac adrenergic neuron integrity and function in congestive heart failure.


METHODS
Rats were treated with adriamycin (2 mg/kg, s.c.) once a week for 7, 8 and 9 wk. In analyzing cardiac adrenergic neuron function, we assessed alterations of uptake-1, exocytotic release and nonexocytotic metabolic release in relation to progression of heart failure.


RESULTS
LVEF progressively decreased. Cardiac MIBG accumulation (4 hr postinjection) decreased to 53% of control at 7 wk and markedly decreased to 14% of control at 9 wk, accompanied by massive pleural effusions. Reduction of MIBG accumulation in the lung and spleen, which are adrenergic-rich organs similar to the heart, were less pronounced compared to reduction in the heart. There was no difference in cardiac uptake of 3H-norepinephrine between the control and 8-wk groups. Cardiac uptake of 3H-norepinephrine decreased 91.0% in the control and 90.8% in the 8 wk group by pretreatment of desipramine, indicating no difference in the uptake-1 component.


CONCLUSIONS
Congestive heart failure due to adriamycin cardiomyopathy progressively accelerates exocytotic release of norepinephrine predominantly from cardiac adrenergic neurons, but neuronal uptake function is not disturbed so long as heart failure is not advanced. In the advanced stage, nonexocytotic metabolic release is induced specifically in cardiac adrenergic neurons due to energy depletion and norepinephrine release markedly increases.
D019797:3-Iodobenzylguanidine; D000818:Animals; D000903:Antibiotics, Antineoplastic; D001345:Autoradiography; D004317:Doxorubicin; D006321:Heart / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000294:innervation; D006333:Heart Failure / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000503:physiopathology; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D011875:Radionuclide Angiography; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D013565:Sympatholytics; D014316:Tritium
D000903:Antibiotics, Antineoplastic; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D013565:Sympatholytics; D014316:Tritium; D019797:3-Iodobenzylguanidine; D004317:Doxorubicin; D009638:Norepinephrine