Key result
Prolonged adriamycin treatment in rats led to a decreased inotropic response to beta-adrenoceptor stimulation and reduced baroreflex control, preceding congestive heart failure.
Early autonomic impairment in anthracycline rat models; leaves open whether beta-adrenergic or baroreflex changes precede human cardiotoxicity.
Cardiac contractile function and hemodynamic parameters of control and adriamycin-treated (2 mg/kg once a week for 10 weeks) rats were studied both in the anesthetized (hexenal, 20 mg/kg) and conscious state. Radiolabelled microspheres (diameter, 15 microns) were used to measure systemic and regional hemodynamics. No significant differences between the control and adriamycin-treated groups in cardiac contractile function, total peripheral resistance, and regional blood flow (except muscles) was found in anesthetized animals. In the conscious state, a significantly higher (+70%) total peripheral resistance combined with lower blood flow in the skin and spleen was observed in adriamycin-treated rats. The response of the heart rate to changes in the arterial pressure induced by nitroglycerin and phenylephrine injection was greatly diminished after adriamycin treatment. Isoprenaline (0.64 micrograms.kg-1.min-1) increased left ventricular contractile indices approximately twofold and heart rate by 30% in the control group, while in adriamycin-treated rats only minor changes in these parameters were observed. However, cardiac output rose by 36% and total peripheral resistance fell by 36% in these animals. Results show that prolonged adriamycin treatment leads to decreased inotropic response to beta-adrenoceptor stimulation and reduced baroreflex control. These changes occur in the stage preceding congestive heart failure.
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Gorodetskaya et al. (1990) studied this question. Adriamycin vs. Control was evaluated on Cardiac contractile function and hemodynamic parameters. Prolonged adriamycin treatment in rats led to a decreased inotropic response to beta-adrenoceptor stimulation and reduced baroreflex control, preceding congestive heart failure.
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