Acute effects of doxorubicin (adriamycin) on left ventricular function in dogs

Although chronic doxorubicin (adriamycin) cardiotoxicity often is attributed to repeated episodes of acute myocardial injury, the acute effects of doxorubicin on in vivo left ventricular performance have not been studied in a carefully controlled setting. Accordingly, we recorded high-fidelity left ventricular pressures and segmental dimensions before and after either intravenous or intracoronary doxorubicin in twelve open-chest dogs. Propranolol was administered to prevent reflex sympathetic stimulation, and heart rate was held constant by atrial pacing. Intravenous doxorubicin (1.5 mg/kg) (n = 6) caused significant decreases in all measured indices of myocardial contractility, in association with a large decrease in left ventricular systolic pressure (125 +/- 28 and 81 +/- 23 mm Hg before and 5 min after doxorubicin, respectively, P less than 0.01). Intracoronary doxorubicin (0.075 to 0.3 mg/kg) (n = 6) caused similar decreases in percent segment shortening (from 19 +/- 7 to 16 +/- 8, P less than 0.05), mean normalized shortening rate (from 0.87 +/- 0.34 to 0.71 +/- 0.37 segment lengths/sec, P less than 0.05), and peak positive left ventricular dP/dt (by 10 +/- 11%, P less than 0.07), although left ventricular systolic pressure was only modestly decreased (126 +/- 20 and 113 +/- 17 mm Hg before and after doxorubicin, respectively, P less than 0.01). Intracoronary doxorubicin also slowed the rate of left ventricular relaxation, as evidenced by an increase in the time constant for isovolumic pressure fall from 32.0 +/- 9.0 to 36.9 +/- 7.5 msec, and significantly altered the relationship between left ventricular pressure and dimension at end-diastole.