Y. Cottin et al., EARLY INCIDENCE OF ADRIAMYCIN TREATMENT ON CARDIAC PARAMETERS IN THE RAT, Canadian journal of physiology and pharmacology, 72(2), 1994, pp. 140-145
To evaluate the early effect of low doses of adriamycin (ADR) on cardi
ac parameters, male Wistar rats were injected with ADR (1 mg.kg(-1).da
y(-1)) or saline for 10 days. Seven days later, T-1 and T-2 relaxation
times were determined in left ventricular (LV) free wall, septum, and
thigh muscle samples. In another experiment, performed on isolated wo
rking hearts of rats pretreated with ADR, LV performance was determine
d along with an index of myocardial lipid peroxidation in this tissue.
Lipid peroxidation was enhanced (p <0.05). This change was not associ
ated with a reduced LV performance, since both aortic and cardiac flow
s 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). T-1 increased in the LV free wall (665 +/- 3 t
o 696 +/- 5 ms, p < 0.001) and in the septum (657 +/- 3 to 696 +/- 5 m
s, p < 0.01), while T-2 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 si
gnificantly increased. No modification was observed in the thigh muscl
e samples. Thus, modifications of T-1 and T-2 relaxation times followi
ng ADR treatment are associated with biochemical changes implicating l
ipid peroxidation. These changes in relaxation times appeared earlier
than hemodynamic deterioration and could provide a basis for the appli
cation of proton nuclear magnetic resonance imaging in the early detec
tion of cardiac ADR toxicity.