The Effects of Dobutamine, Propranolol and Nitroglycerin on an Experimental Canine Model of Congestive Heart Failure.

Abstract

ABSTRACT-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±0.041/min.Systemic vascular resistance (SVR) increased from 9618 ± 585 to 16492 ± 1213 dynes • sec/cm5 and right atrial pressure (RAP) increased from 2.5-L0.2 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 Vma, 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.

Beneficial hemodynamic effects of nicorandil in a canine model of acute congestive heart failure: Comparison with nitroglycerin and cromakalim

“…Experimental congestive heart failure was prepared according to the previous report [7] with some modifications. Experimental congestive heart failure was prepared according to the previous report [7] with some modifications.…”

“…After completion of the surgical preparations, the dogs were allowed to stabilize for at least 30 min without intervention. Experimental congestive heart failure was prepared according to the previous report [7] with some modifications. After baseline hemodynamics was recorded, 1 mL of saponin solution at a concentration of 0.125 or 0.25 mg/mL was injected for 30 sec into each of the LCX and the LAD via a catheter during temporary occlusion of the artery.…”

“…The dose of saponin was selected considering the area of distribution of the coronary artery or the level of basal coronary blood flow. Administration of saponin usually resulted in serious myocardial damage [7], which was evident from loss of reactive hyperemia, a marked decrease in segment shortening and subsequent appearance of gradually darkening of the myocardium within the saponininjected area probably due to diapedesis. When such appropriate myocardial damage was not obtained, an injection of saponin was repeated.…”

“…In the present study, we examined comparative effects of nicorandil, nitroglycerin and cromakalim, a specific K+ATP channel opener [22, 231, on systemic and coronary hemodynamics and cardiac performance in an experimental model of congestive heart failure [7]. The model has been characterized by global left ventricular dysfunction with lowered cardiac output and increased peripheral vascular tone, and has been shown to have potential for differentiating or evaluating the effects of drugs on acute congestive heart failure.…”