A mrinone has been a great forerunner of noncatechol and nonglycoside novel cardiotonic agents and given an extraordinary strong impact in the development of novel cardiotonic agents. Unexpectedly, amrinone failed to rescue the patients with chronic heart failure, thereby produced a prominent paradigm shift from inotropic to cardioprotective therapy, and contributed to advances in the current p...

a,-Adrenoceptor stimulation of rat left ventricular papillary muscles by phenylephrine in the presence of propranolol resulted in rapid breakdown of phosphatidylinositol 4,5-bisphosphate (PI-4,5-Pj) and a triphasic inotropic response in a concentration-dependent manner. The release of inositol trisphosphate (IP,) was maximum within 30 seconds and remained high for at least 30 minutes. The IP3 f...

alpha 1-Adrenoceptor stimulation of rat left ventricular papillary muscles by phenylephrine in the presence of propranolol resulted in rapid breakdown of phosphatidylinositol 4,5-bisphosphate (PI-4,5-P2) and a triphasic inotropic response in a concentration-dependent manner. The release of inositol trisphosphate (IP3) was maximum within 30 seconds and remained high for at least 30 minutes. The ...

Some evidence indicates that the inotropic effect of cardiac glycosides occurs at concentrations too low to affect Na+,K+-ATPase activity. This suggests that some receptor other than Na+,K+-ATPase mediates the inotropic effect. We studied ouabain binding to sarcolemma-enriched preparations from canine ventricle under conditions known to promote binding to Na+,K+-ATPase. Profiles for binding and...

OBJECTIVES The study was designed to evaluate the functional impact of nitric oxide (NO) generation within the myocardium on cardiac contraction in the failing human heart. BACKGROUND Heart failure is associated with activation of cytokines and expression of inducible nitric oxide synthase (NOS II), which generates NO from L-arginine. Nitric oxide has been shown to modulate myocardial perform...

BACKGROUND Chronic stress is associated with cardiac remodeling; however the mechanisms have yet to be clarified. OBJECTIVE The purpose of this study was test the hypothesis that chronic stress promotes cardiac dysfunction associated to L-type calcium Ca2+ channel activity depression. METHODS Thirty-day-old male Wistar rats (70 - 100 g) were distributed into two groups: control (C) and chro...

The effects of intravenous administration of sodium nitroprusside to a donor dog on cardiac pacemaker activity and contractility were investigated in a cross-circulated dog heart preparation; i.e., the isolated atrial muscle was perfused with blood from a pentobarbital anesthetized donor dog. Intravenous administration of nitroprusside (1-10 micrograms/Kg) caused a hypotension with tachycardia,...

Perfusion of isolated rat heart with L-methionine produced a positive inotropic effect that was temporally preceded, as well as accompanied, by an increase of methyl group incorporation into N-methylated phospholipids of the myocardium. Maximal increase in contractile force development was associated with maximal methyl group incorporation. Both parameters showed a dose-related dependence on me...

The contractile and biochemical effects of the divalent cation ionophore A23187 were studied in isolated perfused guinea pig and rat ventricles. A23187 increased both cyclic adenosine 3':5'monophosphate (cyclic AMP) and cyclic guanosine 3':5'-monophosphate (cyclic GMP) concentrations in guinea pig ventricles. Associated with these changes in nucleotide content were positive inotropic effects an...

Heart failure is a relatively important public health problem due to its increasing incidence, poor prognosis, and frequent need of re-hospitalization. Intravenous positive inotropic agents play an important role in treating acute decompensation of patients with heart failure due to left ventricular systolic dysfunction. Although frequently used, the inotropic agents beta-adrenergic agonists an...