Several clinical studies suggest substantial limitations of currently available positive inotropic substances, including beta1-adrenoceptor agonists and phosphodiesterase III inhibitors in the short- and long-term treatment of heart failure. The reasons for these detrimental effects are related to the mechanism of action of these drugs, including increases in intracellular Ca2+ with subsequent ...

The effects of sevoflurane on myocardial contraction and relaxation are poorly understood. Therefore, we studied the effects of equianaesthetic concentrations (0.5, 1, 1.5, 2 and 2.5 MAC) of sevoflurane, isoflurane and halothane on inotropic and lusitropic (myocardial relaxation) variables, and post-rest potentiation in rat left ventricular papillary muscles in vitro. Sevoflurane and isoflurane...

Optically active isomers of N-methy1-2-(2-(2-(4-phenylpiperazino)ethoxy)phenyl)thiazolidine3-carboxamides(( + )-2 and(-)-2) have been synthesized and tested for positive inotropic activity. The racemic thiocarboxamide((•})-3) was resolved into the enantiomers(( + )-3 and(•E)-3) via the Land D-N-(2-naphthylsulfonyl)prolyl derivatives ((+ )-4 and (-)-4). Conversion of the thiocarboxamides (( + )-...

Inotropes have been fundamental to resuscitation of acute cardiogenic shock for decades. Heart failure and cardiogenic shock, in severe cases, are syndromes characterized in many patients by a reduction in myocardial contractile force. While inotropes successfully increase cardiac output, their use has been plagued by excessive mortality due to increased tachycardia and myocardial oxygen consum...

v the neuroendocrine response, which was once believed to be a compensatory reaction of the organism to counteract the ‘failure’ conditions, is now considered a detrimental response of the body. As such, it is recommended that this response be treated; v positive inotropic drugs, which were considered the logical treatment solution for the failing heart, do — paradoxically — increase mortality ...

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...

The most common use of inotropes is among hospitalized patients with acute decompensated heart failure, with reduced left ventricular ejection fraction and with signs of end-organ dysfunction in the setting of a low cardiac output. Inotropes can be used in patients with severe systolic heart failure awaiting heart transplant to maintain hemodynamic stability or as a bridge to decision. In cases...

The present study investigated the influences of inotropic intervention on the intracellular Ca2+ transient (intracellular Ca2+ concentration ([Ca2+]i)) and contractile twitch. Isometric twitch and [Ca2+]i (fura 2 ratio method) were measured simultaneously (1 Hz, 37 degrees C) after stimulation with Ca2+ (0.9-3.2 mM), the cardiac glycoside ouabain (Oua; 0.1 microM), the beta1- and beta2-adrenoc...

The differential effects of a selective kappa- (κ-) opioid receptor agonist, U50488, were elucidated by monitoring the contraction of isolated guinea pig atrial and ventricular muscles. In electrically driven left atria, U50488 in nanomolar concentration range decreased the contractile force. Norbinaltorphimine (norBNI), a selective κ-receptor antagonist, and pertussis toxin (PTX) abolished the...

Sixteen healthy men were evaluated for left ventricular performance changes and beta-blockade after therapeutic oral doses of disopyramide and propranolol administered alone and concurrently. The volunteers were randomly assigned to receive one of two drug treatment regimens that differed in the sequence and duration of administration of the drugs. Left ventricular function was assessed by echo...