Cardiac energy metabolism at several stages of adriamycin-induced heart failure in rats.
To evaluate the changes in myocardial energy metabolism in the progressively failing myocardium, we measured myocardial level of adenosine triphosphate (ATP) using high-performance liquid chromatography (HPLC), and levels of lactate, alanine and free carnitine using 1H-nuclear magnetic resonance (NMR) spectroscopy in rats injected with adriamycin. The drug was injected intraperitoneally 2.5 mg/kg 6 times over a period of 2 weeks. Measurements were obtained 1 day (1 d), 3 weeks (3 w) and 6 weeks (6 w) after the last injection. No deaths were observed until the end of the 3rd week. The cumulative mortality rate 6 weeks after the last injection was 48%. ATP and free carnitine levels were not significantly changed at 1 d, while myocardial lactate was increased by 33% from the control values (P < 0.05). Lactate levels were reduced significantly, but not progressively, at 3 w (31% of control values) and at 6 w (69% of control values). Similar changes were observed in alanine levels. Free carnitine levels were progressively decreased at 3 w (74% of control values) and at 6 w (57% of control values). Changes in ATP levels paralleled those of free carnitine. Data suggest that a decrease in the myocardial level of free carnitine may be involved in progression of the heart failure induced by adriamycin in rats.
Kawasaki
N
N
First Department of Internal Medicine, Fukui Medical School, Japan.
Lee
J D
JD
Shimizu
H
H
Ishii
Y
Y
Ueda
T
T
D000255:Adenosine Triphosphate / Q000032:analysis; D000409:Alanine / Q000097:blood; D000818:Animals; D002303:Cardiac Output, Low / Q000378:metabolism*; D002331:Carnitine / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D018450:Disease Progression; D004317:Doxorubicin; D019344:Lactic Acid / Q000097:blood; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019344:Lactic Acid; D004317:Doxorubicin; D000255:Adenosine Triphosphate; D000409:Alanine; D002331:Carnitine