阿霉素心肌病中心肌底物利用与左心室功能

Myocardial substrate utilization and left ventricular function in adriamycin cardiomyopathy.

作者信息

Wakasugi S, Fischman A J, Babich J W, Callahan R J, Elmaleh D R, Wilkinson R, Strauss H W

机构信息

Department of Radiology, Massachusetts General Hospital, Boston 02114.

出版信息

J Nucl Med. 1993 Sep;34(9):1529-35.

PMID:8355075

Abstract

We evaluated alterations of substrate utilization in a rat model of adriamycin cardiomyopathy with deteriorating left ventricular function. Rats were treated with adriamycin (2 mg/kg), once a week for 6, 8, 9 and 10 wk. Fluorine-18-F-deoxyglucose (18F-FDG) and 125I-beta-methyl-branched fatty acid (125I-BMIPP) were used as tracers of glucose and fatty acid metabolism and 99mTc-hexakis (2-methoxyisobutyl-isonitrile) (99mTc-MIBI) was used as a myocardial blood flow tracer. Left ventricular ejection fraction (LVEF) calculated from gated blood pool images was used as an indicator of cardiac function. LVEF was normal in the 6-wk group (78.0% +/- 4.8%), abruptly decreased in the 8-wk group (43.1% +/- 10.1%) and further deteriorated in the 9-wk group (27.6% +/- 13.4%). Accumulation of 18F-FDG (%kgID/g) in the hearts of adriamycin treated animals progressively decreased compared to controls (2.19% +/- 0.38%); 1.47% +/- 0.42% (p < 0.01) at 6 wk, 1.22% +/- 0.27% (p < 0.001) at 8 wk, 0.69% +/- 0.56% (p < 0.001) at 9 wk and 0.50% +/- 0.08% (p < 0.001) at 10 wk. This decrease occurred earlier than the deterioration in LVEF. Myocardial accumulation of 125I-BMIPP decreased in the advanced stages of adriamycin cardiomyopathy and was well correlated with the decrease in 18F-FDG accumulation. However, the decrease was less profound than for 18F-FDG; 53.7% +/- 9.8% versus 31.6% +/- 25.4% of control at 9 wk (p = NS), 49.5% +/- 15.3% versus 22.6% +/- 3.5% of control at 10 wk (p < 0.05). Accumulation of 99mTc-MIBI did not differ between controls and the adriamycin treated groups. There were no differences in blood glucose levels between controls and adriamycin treatment groups. Both glucose and fatty acid utilization are decreased in adriamycin-induced cardiomyopathy and these critical impairments in energy metabolism are associated with heart failure. Impaired myocardial glucose utilization measured with 18F-FDG may be a particularly sensitive marker of adriamycin cardiomyopathy.

摘要

我们在左心室功能逐渐恶化的阿霉素性心肌病大鼠模型中评估了底物利用的改变。大鼠每周接受一次阿霉素（2mg/kg）治疗，持续6、8、9和10周。氟-18-F-脱氧葡萄糖（18F-FDG）和125I-β-甲基支链脂肪酸（125I-BMIPP）用作葡萄糖和脂肪酸代谢的示踪剂，99mTc-六甲基（2-甲氧基异丁基异腈）（99mTc-MIBI）用作心肌血流示踪剂。从门控血池图像计算出的左心室射血分数（LVEF）用作心功能指标。6周组的LVEF正常（78.0%±4.8%），8周组突然下降（43.1%±10.1%），9周组进一步恶化（27.6%±13.4%）。与对照组相比，阿霉素治疗动物心脏中18F-FDG的蓄积（%kgID/g）逐渐减少；6周时为1.47%±0.42%（p<0.01），8周时为1.22%±0.27%（p<0.001），9周时为0.69%±0.56%（p<0.001），10周时为0.50%±0.08%（p<0.001）。这种减少比LVEF的恶化更早出现。阿霉素性心肌病晚期心肌中125I-BMIPP的蓄积减少，且与18F-FDG蓄积的减少密切相关。然而，这种减少不如18F-FDG明显；9周时为对照组的53.7%±9.8%，而18F-FDG为31.6%±25.4%（p=无显著性差异），10周时为对照组的49.5%±15.3%，而18F-FDG为22.6%±3.5%（p<0.05）。对照组和阿霉素治疗组之间99mTc-MIBI的蓄积没有差异。对照组和阿霉素治疗组之间血糖水平没有差异。阿霉素诱导的心肌病中葡萄糖和脂肪酸的利用均降低，这些能量代谢的关键损害与心力衰竭有关。用18F-FDG测量的心肌葡萄糖利用受损可能是阿霉素性心肌病的一个特别敏感的标志物。