Cardiac parasympathetic activity reduces susceptibility to potentially lethal ventricular arrhythmias in heart failure and ischemic heart disease. This influence is mediated in large part by antagonism of the adverse cardiac effects of sympathetic overactivity ("indirect" parasympathetic activity) in addition to the "direct" effects of muscarinic stimulation. Nitric oxide modulates parasympathe...

Tension duration curves recorded during isometric contractions of toad ventricular strips were studied under a variety of conditions. Changes recorded in these curves during inotropic responses could be divided into two classes: (a) those in which the time required to reach peak tension (t(p)) was decreased and the twitch duration shortened. (b) those in which t(p) was either unaltered or incre...

Acute Heart failure (AHF), clinical signs of low cardiac output, therapy with positive inotropic drug for cardiac care is mandatory. Three classes of inotropic drugs are currently available, like β-adrenergic agonists (especially dobutamine), phosphodiesterase (PDE) inhibitors (such as milrinone) and Ca sensitizers (levosimendan). The mechanisms of action of these drugs, and important issues re...

Contractile activity was recorded from isolated canine ventricular muscle exposed to acetylstrophanthidin (AS), 0.5 to 2 X 10(-7) g/ml. Development of the positive inotropic effect of AS was accompanied by the appearance of aftercontractions (AC) coupled to the driven responses. The amplitudes of AC increased with the number of preceding beats. Test beats occurring during the ascending limb of ...

Editorial Why inotropes continue to disappoint in heart failure Despite their low therapeutic index, cardiac glycosides have been used for centuries for the treatment of heart failure. In the past two decades pharmaceutical companies have developed several new orally active drugs, which like the glycosides have positive inotropic activity in vitro. It was hoped that they would replace the glyco...

Endothelin, a 21-amino acid vasoactive peptide, is among the most potent positively inotropic agents yet described in mammalian heart. Having demonstrated that endothelin's inotropic effect is due, in part, to an apparent sensitization of cardiac myofilaments to intracellular calcium, we determined whether this could be due to a rise in intracellular pH (pHi). In isolated adult rat ventricular ...

In blood-perfused isolated canine atrium preparations, single injections of dibutyryl cyclic AMP at a dose range of 1 to 30 mg were made into the cannulated sinus node artery. At doses above 3 mg, dibutyryl cyclic AMP induced a biphasic chronotropic and inotropic response; there was a slight and rapid negative chronotropic and inotropic response, followed by a long-lasting positive chronotropic...

Amrinone is a new synthetic drug that increases contractile strength of mammalian heart muscle; however, its mechanism of positive inotropic action has not been determined. We now report that amrinone (0.053-5.3 mM) consistently restores typical slow response electromechanical activity fo K+-depolarized atrial and ventricular myocardial preparations from guniea pigs. This action was blocked in ...

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) may serve as a new assay for drug testing in a human context, but their validity particularly for the evaluation of inotropic drug effects remains unclear. In this blinded analysis, we compared the effects of 10 indicator compounds with known inotropic effects in electrically stimulated (1.5 Hz) hiPSC-CM-derived 3-dimensional...

We studied the inotropic response to dopamine and digoxin in 20 patients with severe sepsis and left ventricular failure. Left ventricular failure was defined as a left ventricular stroke work index less than or equal to 40 g.m/m2 at a pulmonary artery wedge pressure greater than or equal to 15 mm Hg. Hemodynamic assessment was obtained before and following administration of digoxin 10 microgra...