Kurata C, Okayama K, Wakabayashi Y, Shouda S, Mikami T, Tawarahara K, Sugiyama T
Department of Medicine III, Hamamatsu University School of Medicine, Hamamatsu Red Cross Hospital, Japan.
J Nucl Med. 1997 Nov;38(11):1677-80.
Cardiac autonomic neuropathy can be a cause of sudden death in patients with diabetes mellitus. Clinical evaluation methods for diabetic cardiac sympathetic neuropathy have not been established. Using 125I-metaiodobenzylguanidine (MIBG) and streptozotocin (STZ)-induced diabetic rats, we evaluated cardiac sympathetic neuropathy and the effects of aldose reductase inhibitor (ARI).
Myocardial MIBG uptake was measured 4 hr after injection in the following groups: control rats, rats treated with insulin or ARI (epalrestat, 100 mg/kg/day) from immediately 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 therapy started immediately after STZ injection.
Myocardial MIBG uptake was significantly lower in diabetic rats than in control rats; the reduction was marked in the subendocardial myocardium. Myocardial norepinephrine content was increased significantly in diabetic rats compared with control rats. Decreased MIBG uptake and increased norepinephrine content in diabetic myocardium were completely prevented by insulin therapy started immediately after STZ injection and partially, but significantly, by ARI administered from immediately after STZ injection. Heterogeneous MIBG distribution also disappeared with the ARI therapy. In contrast, diabetic rats treated with insulin or ARI therapy started 4 wk after STZ injection showed no improvement in MIBG uptake.
These results suggest that MIBG abnormalities observed in diabetic rats may reflect diabetic cardiac sympathetic neuropathy independently of cardiomyopathy, nephropathy or coronary heart disease secondary to diabetes and that MIBG imaging may be useful for clinical assessment of cardiac sympathetic neuropathy.
心脏自主神经病变可能是糖尿病患者猝死的原因之一。糖尿病性心脏交感神经病变的临床评估方法尚未确立。我们使用125I-间碘苄胍（MIBG）和链脲佐菌素（STZ）诱导的糖尿病大鼠，评估了心脏交感神经病变及醛糖还原酶抑制剂（ARI）的作用。
在注射后4小时测量以下几组大鼠的心肌MIBG摄取：对照组大鼠、在STZ注射后立即至4周用胰岛素或ARI（依帕司他，100mg/kg/天）治疗的大鼠以及在4-8周用胰岛素或ARI治疗的大鼠。在STZ注射后立即开始或未开始ARI治疗的对照和糖尿病大鼠中评估心肌MIBG分布和去甲肾上腺素含量。
糖尿病大鼠的心肌MIBG摄取明显低于对照大鼠；心内膜下心肌的减少更为明显。与对照大鼠相比，糖尿病大鼠的心肌去甲肾上腺素含量显著增加。STZ注射后立即开始的胰岛素治疗可完全防止糖尿病心肌中MIBG摄取减少和去甲肾上腺素含量增加，而STZ注射后立即给予的ARI可部分但显著地防止这种情况。ARI治疗后，MIBG的不均匀分布也消失了。相比之下，在STZ注射4周后开始用胰岛素或ARI治疗的糖尿病大鼠，其MIBG摄取没有改善。
这些结果表明，糖尿病大鼠中观察到的MIBG异常可能独立于糖尿病继发的心肌病、肾病或冠心病反映糖尿病性心脏交感神经病变，并且MIBG成像可能有助于心脏交感神经病变的临床评估。
