title: Myocardial substrate utilization and left ventricular function in adriamycin cardiomyopathy.
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.
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston 02114.
authors.forename: S
authors.initials: S
authors.lastname: Wakasugi
authors.forename: A J
authors.initials: AJ
authors.lastname: Fischman
authors.forename: J W
authors.initials: JW
authors.lastname: Babich
authors.forename: R J
authors.initials: RJ
authors.lastname: Callahan
authors.forename: D R
authors.initials: DR
authors.lastname: Elmaleh
authors.forename: R
authors.initials: R
authors.lastname: Wilkinson
authors.forename: H W
authors.initials: HW
authors.lastname: Strauss
mesh_terms: D000818:Animals; D003847:Deoxyglucose / Q000031:analogs & derivatives; D004317:Doxorubicin / Q000009:adverse effects*; D005227:Fatty Acids; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D015637:Gated Blood-Pool Imaging; D006321:Heart / Q000000981:diagnostic imaging*; D006333:Heart Failure / Q000139:chemically induced* / Q000000981:diagnostic imaging*; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017256:Technetium Tc 99m Sestamibi; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D005227:Fatty Acids; D005462:Fluorine Radioisotopes; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; C049338:iodofiltic acid; D019788:Fluorodeoxyglucose F18; D004317:Doxorubicin; D017256:Technetium Tc 99m Sestamibi; D003847:Deoxyglucose