CARDIAC SYMPATHETIC NEUROPATHY AND EFFECTS OF ALDOSE REDUCTASE INHIBITOR IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

Cardiac autonomic neuropathy can be a cause of sudden death in patient s with diabetes mellitus. Clinical evaluation methods for diabetic car diac sympathetic neuropathy have not been established. Using I-125-met aiodobenzylguanidine (MIBG) and streptozotocin (STZ)-induced diabetic rats, we evaluated cardiac sympathetic neuropathy and the effects of a ldose reductase inhibitor (ARI). Methods: Myocardial MIBG uptake was m easured 4 hr after injection in the following groups: control rats, ra ts treated with insulin or ARI (epalrestat, 100 mg/kg/day) from immedi ately to 4 wk after STZ injection and rats treated with insulin or ARI from 4-8 wk. Myocardial MIBG distribution and norepinephrine content were evaluated in the control and diabetic rats with or without ARI th erapy started immediately after STZ injection. Results: Myocardial MIB G uptake was significantly lower in diabetic rats than in control rats ; the reduction was marked in the subendocardial myocardium. Myocardia l norepinephrine content was increased significantly in diabetic rats compared with control rats. Decreased MIBG uptake and increased norepi nephrine content in diabetic myocardium were completely prevented by i nsulin therapy started immediately after STZ injection and partially, but significantly, by ARI administered from immediately after STZ inje ction. Heterogeneous MIBG distribution also disappeared with the ARI t herapy. In contrast, diabetic rats treated with insulin or ARI therapy started 4 wk after STZ injection showed no improvement in MIBG uptake . Conclusion: These results suggest that MIBG abnormalities observed i n diabetic rats may reflect diabetic cardiac sympathetic neuropathy in dependently of cardiomyopathy, nephropathy or coronary heart disease s econdary to diabetes and that MIBG imaging may be useful for clinical assessment of cardiac sympathetic neuropathy.