Hemodynamic response of a canine model of chronic heart failure to intravenous dobutamine, nitroprusside, enalaprilat, and digoxin.
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 micrograms/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 micrograms/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 treatment of this disease state.
Sabbah
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HN
Henry Ford Heart and Vascular Institute, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, Michigan 48202.
Levine
T B
TB
Gheorghiade
M
M
Kono
T
T
Goldstein
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S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004077:Digoxin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004280:Dobutamine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D015773:Enalaprilat / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D009599:Nitroprusside; D004280:Dobutamine; D004077:Digoxin; D015773:Enalaprilat