Early incidence of adriamycin treatment on cardiac parameters in the rat.
To evaluate the early effect of low doses of adriamycin (ADR) on cardiac parameters, male Wistar rats were injected with ADR (1 mg.kg-1.day-1) or saline for 10 days. Seven days later, T1 and T2 relaxation times were determined in left ventricular (LV) free wall, septum, and thigh muscle samples. In another experiment, performed on isolated working hearts of rats pretreated with ADR, LV performance was determined along with an index of myocardial lipid peroxidation in this tissue. Lipid peroxidation was enhanced (p < 0.05). This change was not associated with a reduced LV performance, since both aortic and cardiac flows measured in working heart preparations were similar between control and treated rats. However, the coronary flow was significantly reduced (control group, 21 +/- 1 mL.min-1.g-1, ADR group, 15 +/- 1 mL.min-1.g-1; p < 0.001). T1 increased in the LV free wall (665 +/- 3 to 696 +/- 5 ms, p < 0.001) and in the septum (657 +/- 3 to 696 +/- 5 ms, p < 0.01), while T2 increased only in the LV free wall (50.8 +/- 0.9 to 53.1 +/- 0.6 ms, p < 0.05). Myocardial water content was also significantly increased. No modification was observed in the thigh muscle samples. Thus, modifications of T1 and T2 relaxation times following ADR treatment are associated with biochemical changes implicating lipid peroxidation. These changes in relaxation times appeared earlier than hemodynamic deterioration and could provide a basis for the application of proton nuclear magnetic resonance imaging in the early detection of cardiac ADR toxicity.
Cottin
Y
Y
Laboratoire de physiopathologie et pharmacologie cardiovasculaires expérimentales, Faculté de médecine, Dijon, France.
Ribuot
C
C
Maupoil
V
V
Godin
D
D
Arnould
L
L
Brunotte
F
F
Rochette
L
L
D000818:Animals; D001834:Body Water / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects
D004317:Doxorubicin