The effects of dobutamine, propranolol and nitroglycerin on an experimental canine model of congestive heart failure.
A new experimental model of acute congestive heart failure was established in open-chest dogs, and it was employed to examine the effects of dobutamine, propranolol and nitroglycerin. The model was induced by intracoronary administration of saponin, volume loading and intravenous infusion of methoxamine. Left ventricular end-diastolic pressure (LVEDP) increased from 7.9 +/- 0.6 to 24.2 +/- 1.4 mmHg, and aortic blood flow (AoF) decreased from 0.89 +/- 0.06 to 0.53 +/- 0.04 l/min. Systemic vascular resistance (SVR) increased from 9618 +/- 585 to 16492 +/- 1213 dynes.sec/cm5 and right atrial pressure (RAP) increased from 2.5 +/- 0.2 to 4.2 +/- 0.4 mmHg. Furthermore, Vmax decreased from 71.6 +/- 5.1 to 45.8 +/- 2.9 1/sec, and the time constant of left ventricular pressure decay (T) increased from 40.0 +/- 2.6 to 90.2 +/- 7.9 msec. These hemodynamic changes were stable for up to 80 min. Dobutamine improved cardiac function by increasing Vmax and by decreasing T. Consequently, dobutamine increased AoF and decreased LVEDP, while there was no change in SVR. Nitroglycerin reduced LVEDP, SVR and T; increased AoF; and did not change Vmax. Propranolol produced no improvement in the hemodynamics or cardiac function. These results indicate that the present congestive heart failure model is characterized by global left ventricular dysfunction with lowered cardiac output and increased peripheral vascular tone, and it is beneficial for evaluating the pharmacological properties of drugs for acute congestive heart failure.
Kamijo
T
T
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Tomaru
T
T
Miwa
A Y
AY
Nakamura
F
F
Kido
H
H
Sugimoto
T
T
Uchida
Y
Y
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D004280:Dobutamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D007269:Injections, Intra-Arterial; D008297:Male; D008729:Methoxamine / Q000633:toxicity; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D004280:Dobutamine; D011433:Propranolol; D005996:Nitroglycerin; D008729:Methoxamine