epalrestat and Heart-Diseases

This study was undertaken to examine the effects of aldose reductase inhibitor (ARI) and vitamin B12 (VB12) on myocardial uptake of iodine-123 metaiodobenzylguanidine (MIBG) in patients with diabetic autonomic disorder. Myocardial scintigraphy using 123I-MIBG was performed on 20 healthy volunteers (controls) and 56 patients with non-insulin-dependent diabetes mellitus (NIDDM), in order to obtain the heart/mediastinum ratio in the initial (HMi) and the delayed images (HMd), and the washout rate (%WR). Thirty-four of the 56 NIDDM patients could be diagnosed as having diabetic autonomic disorder by evaluating their scintigraphic findings in comparison with the controls. Seventeen of these 34 patients received 150 mg/day of doses before meals, and the other 17 received 1.5 mg/day of mecobalamin (VB12 group) in three divided doses after meals, for 3-5 months. According to the presence or absence of clinical symptoms of autonomic or peripheral somatic nerve disorder, the patients were subclassified into four groups. group 1=patients, with autonomic symptoms or somatosensory disorder in the ARI group; group 2=patients without autonomic symptoms or somatosensory disorder in the ARI group; group 3=patients with autonomic symptoms or somatosensory disorder in the VB12 group; and group 4=patients without autonomic symptoms or somatosensory disorder in the VB12 group. After completion of the treatment, myocardial scintigraphy was performed again. Comparing the results obtained before and after the treatment, it was seen that ARI improved only the HMi in group 1 (P=0.046), whereas VB12 significantly improved HMi in the group 3 (P=0.018) and HMi, HMd and %WR in group 4 (P=0.043, P=0.018 and P=0.043, respectively). We conclude that VB12 is more efficacious than ARI in the treatment of diabetic cardiovascular autonomic disorder.

Topics: 3-Iodobenzylguanidine; Adult; Aged; Aged, 80 and over; Aldehyde Reductase; Autonomic Nervous System Diseases; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Enzyme Inhibitors; Female; Heart; Heart Diseases; Humans; Male; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Rhodanine; Thiazolidines; Vitamin B 12

1. To determine the effects of an aldose reductase inhibitor (ARI) on diabetes-induced cardiac sympathetic disturbance, the effects of (E)-3-carboxymethyl-5-[(2E)-methyl-3-phenylpropenylidene] rhodamine (ONO-2235), an aldose reductase inhibitor, as well as insulin on the responsiveness to the transmural sympathetic nerve stimulation (TNS) and norepinephrine (NE) of isolated right atria of streptozotocin-induced diabetic rats were investigated. 2. The responsiveness to TNS of 8-week diabetic rats decreased, and those of 12-week diabetic rats severely decreased. The responses to NE also decreased 8 weeks or more after the induction of diabetes. 3. In 8-week diabetic rats, the insulin treatment completely restored the responsiveness to TNS, while ARI treatment partially restored the responsiveness to TNS. In 12-week diabetic rats, the single treatment with insulin or ARI only slightly restored the responsiveness to TNS, while the combination treatment with insulin and ARI almost completely restored the responsiveness to TNS in 12-week diabetic rats. 4. From the present results, the following may be concluded: Sympathetic nerve responses of right atria decreases in diabetic rats, and these changes may be related to hypoinsulinemia and abnormal polyol pathway. Although a serious sympathetic disturbance was only slightly improved by insulin or ARI, the combination of insulin and ARI produced more remarkable improvement of this disturbance.

Topics: Aldehyde Reductase; Animals; Blood Chemical Analysis; Body Weight; Diabetes Mellitus, Experimental; Electric Stimulation; Heart; Heart Diseases; Heart Rate; Insulin; Male; Norepinephrine; Rats; Rats, Inbred Strains; Rhodanine; Sympathetic Nervous System; Thiazolidines