Levosimendan is a calcium sensitizer developed for the treatment of heart failure. It increases contractile force by enhancing the sensitivity of myofilaments to calcium. Besides this sensitizing effect, the drug has also been reported to show some inhibitory action on phosphodiesterase 3 (PDE3). The inotropic effects of levosimendan have been studied on guinea pig paced perfused hearts by usin...

Ammonia (NH(3)) is a common exogenous gas in the atmosphere, as well as an endogenous chemical produced by amino acid catabolism and other pathways in vivo. Physiological and pathophysiological roles of NH(3) in the nervous system have been studied. Recently, endogenous NH(3) has been suggested to be a gas transmitter. However, so far the role of NH(3) in cardiovascular functions has not been r...

Background. Adenosine attenuates f-adrenoceptor-mediated inotropic responses through GTP-binding protein in vitro. The goal of the present study was to test the hypothesis that endogenous adenosine released from the ischemic myocardium blunts the inotropic response to /3-adrenergic stimulation. Methods and Results. In 45 open-chest dogs, the left anterior descending coronary artery was perfused...

1. Synthetic proctolin increases the force but not the rate of heart contractions of Limulus in a timeand dose-dependent manner. The threshold of this effect is 3 X 10~'°M and the ED50 is approximately 10"'M. 2. At concentrations up to 10" M, proctolin has no effect on the rhythmic electrical activity of the isolated cardiac ganglion, and it does not change the simple and compound postsynaptic ...

Prior observations have raised the possibility that dihydropyridine (DHP) agonists directly affect the sarcoplasmic reticulum (SR) cardiac Ca(2+) release channel [i.e., ryanodine receptor (RyR)]. In single-channel recordings of purified canine cardiac RyR, both DHP agonists (-)-BAY K 8644 and (+)-SDZ202-791 increased the open probability of the RyR when added to the cytoplasmic face of the chan...

Glucagon has a positive inotropic effect in normal hearts but is ineffective in animals with chronic cardiac failure. To assess directly the influence of glucagon on the human myocardium, we measured contractility and activation of adenyl cyclase, the enzyme thought to mediate the inotropic action of glucagon, in left ventricular papillary muscles obtained from 12 patients at mitral valve repla...

This study investigated the effects of cardiac glycosides on single-channel activity of the cardiac sarcoplasmic reticulum (SR) Ca2+ release channels or ryanodine receptor (RyR2) channels and how this action might contribute to their inotropic and/or toxic actions. Heavy SR vesicles isolated from canine left ventricle were fused with artificial planar lipid bilayers to measure single RyR2 chann...

1. The effect of the adenosine A(2) receptor (AdoA(2)R) agonist N(6)-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA) on adenosine A(1) receptor (AdoA(1)R)-mediated negative inotropic responses was investigated in rat heart. 2. Hearts from male Wistar rats (250-350 g) were perfused with Krebs'-Henseleit solution at constant flow in non-recirculating Langendorff mode. Hearts we...

BACKGROUND Selective phosphodiesterase (PDE3) inhibitors improve cardiac contractility and may use in congestive heart failure. However, their proarrhythmic potential is the most important side effect. METHODS In this research, we evaluated the potential cardiotonic activity of six new synthesized selective PDE3 inhibitors (6-hydroxy-4-methylquinolin-2(1H)-one derivatives) using the spontaneo...

Cardiogenic shock is associated with substantial morbidity and mortality. Although inotropic support a mainstay of medical therapy for cardiogenic shock, little evidence exists to guide the selection agents in clinical practice.