Hemodynamic response of a canine model of chronic heart failure to intravenous dobutamine, nitroprusside, enalaprilat, and digoxin

摘要

The hemodynamic effects of acute intravenous administration of nitroprusside, dobutamine, enalaprilat, and digoxin was investigated in a canine model of chronic heart failure (CHF) produced by multiple sequential intracoronary microembolizations. Dobutamine (4 µg/kg/min) increased cardiac output (2.4±0.1 vs. 4.0±0.4 l/min; p<.001) and LV ejection fraction (LVEF; 26±1 vs. 30±4; p<.01), and decreased systemic vascular resistance (SVR; 3620±170 vs. 2470±190 dynes sec cm−5; p<.001). Nitroprusside (3 µg/kg/min) acted as a venodilator; it decreased pulmonary artery wedge pressure (16±1 vs. 13±1 mmHg; p<.01) and SVR (3730±440 vs. 3210±280 dynes sec cm−5; NS) but had no effect on cardiac output. Enalaprilat (1.875 mg) produced a significant increase of cardiac output (3.0±0.5 vs. 3.8±0.5 l/min; p<.001) and LVEF (22±1 vs. 30±1; p<.01), and decreased SVR (3280±400 vs. 2450±250 dynes sec cm−5; p<.01). Intravenous digoxin at a cumulative dose of 0.75 mg increased LVEF (23±2 vs. 31±2; p<.01) but had no effect on SVR. These data indicate that this canine model of CHF responds to acute pharmacologic intervention in a manner comparable to that seen in patients with CHF. Accordingly, this model may be a useful tool for the preclinical evaluation of new drugs targeted toward the treatment of CHF and for investigating the mechanisms of action of drugs currently used for the treatm