Acute and Postponed Action of Adriamycin on the Contractile Function and Antioxidant Status of the Myocardium
Functional, biochemical and morphological studies of rat cardiac muscle after single injection of adriamycin (2.2 mg/kg) were carried out. The myocardium was taken for studies in 2 hours and in 2-3 weeks after adriamycin injection. The isolated heart was perfused retrogradely with Krebs solution and left ventricular isovolumic pressure and perfusion pressure were continuously monitored. Two-fold increase in perfusion rate was accompanied by raised developed pressure, heart rate and perfusion pressure which in the given conditions reflected a tone of coronary vessels. The cardiac contractile function of rats that received adriamycin 2 hours before, remained unaltered as compared to control group, however, perfusion pressure was raised by 26%. These hearts responded to H <sub>2</sub>O <sub>2</sub> introduction (100 pM) into coronary vessels by more profound fall in developed pressure, which fell to 31±8% after 40 minutes vs. 61±5% in the control group (p<0.01). In two-three weeks after adriamycin injection, both cardiac contractile function and its responsiveness to oxidative stress induced by H <sub>2</sub>O <sub>2</sub> introduction did not differ from the control, however, perfusion pressure remained elevated and this was accompanied by slowed myocardial relaxation. The myocardial concentration of malonic dialdehyde was moderately increased in adriamycin-treated group in both terms while the activity of antioxidant enzymes (SOD, GPHx and catalase) remained unaltered. Results showed an absence of the direct connection between myocardial antioxidant status and the contractile function changes at adriamycin action.