Objectives: The regulation of cardiac function by catecholamines involves three populations of b-adrenoceptor (b-AR). b and b -AR 1 2 stimulations produce an increase in contractility and b -AR stimulation mediates a negative inotropic effect in human ventricular muscle. 3 Because of the lack of suitable animal models, we have generated transgenic mice with cardiac-specific expression of the hu...

Bacterial endotoxin (lipopolysaccharide) depresses cardiovascular function; however, the mediators and signaling pathways that are responsible for the negative inotropic effects of lipopolysaccharide are not fully known. We used RNA interference to determine the relative role of tumor necrosis factor with respect to mediating the negative inotropic effects of lipopolysaccharide in isolated card...

Previous studies have shown reduced effects of cAMP-dependent positive inotropic agents in the failing human myocardium; thus other cAMP-independent mechanisms of action may be useful to increase force of contraction in this condition. The purpose of this investigation was to determine whether a positive inotropic effect of the cAMP-phosphodiesterase (PDE) inhibitor pimobendan is observed in th...

The effects of piretanide and furosemide on systemic arterial blood pressure and heart rate were examined in the anesthetized dog and the effects on atrial rate and contractile force were assessed in isolated atrial muscle perfused with heparinized arterial blood from a donor dog. When piretanide was administered intravenously to intact dogs, the depressor and bradycardic responses were produce...

The effects of potassium chloride on inotropic and chronotropic activity were investigated in five isolated canine atrium preparations which were suspended in a bath and perfused with arterial blood from the carotid artery of the heparinized support dog. Potassium chloride administered into the cannulated sinus node artery in a dose range of 100 mug-1 mg produced a dose-related negative inotrop...

Postsynaptic alpha 2-adrenoceptors have been reported to exist in various tissues, including vascular smooth muscle. In order to investigate the possibility of their mediating a positive inotropic change and clarify the influence of the thyroid on their responsiveness, we examined the effects of clonidine, a known alpha 2-agonist, on the isolated left atria and femoral vascular beds of rats whi...

To delineate more clearly the importance of altered monovalent cation transport rate in the mediation of the positive inotropic effects of cardiac glycosides, we studied changes in the contractile state and rate of uptake of K+ and Rb+ by monolayer cultures of chick embryo ventricular cells during exposure to and washout of ouabain and dihydro-ouabain. These cardiac glycosides produced a positi...

Clinical Use of Digitalis Glycosides The potential benefit of digoxin therapy in heart failure patients is thought to be related to its positive inotropic effect that increases cardiac output and thereby decreases ventricular filling pressures.2 Although digoxin is undoubtedly an inotropic agent in tissue preparations,3 this effect, in contrast to other inotropic agents, is not consistently tra...

The action of a novel cardiotonic agent N-hydroxy-5,6-dimethoxy-benzo[b]thiophene-2-carboximide hydrochloride (Org 30029) on intracellular aequorin light transients and isometric contractions was investigated in isolated canine ventricular trabeculae. The positive inotropic effect of Org 30029 (30 microM-3 mM) was consistently associated with prolongation of the duration of contraction and an i...

The appropriateness of inotropic therapy in chronic heart failure was examined by critically reviewing five assumptions upon which this form of therapy has been justified. Only the first, that cardiac performance can be acutely improved by inotropic therapy, has been empirically proven. That such acute improvement is sustained appears to be true with non-catecholamine agents whereas the chronic...