Coronary flow regulates cardiac functions, and it has been suggested that endothelial membrane glycosylated proteins are the primary shear stress mechanosensors. Our hypothesis was that if these proteins are the sensors for flow, then intracoronary perfusion of lectins or specific antibodies should differentially depress coronary flow-enhanced responses of different parenchymal cell types such ...

We studied the effects of the local anesthetics, procaine and benzocaine, on the action potential and force of canine ventricular muscle and Purkinje fibers. In ventricular muscle, procaine often shifted the plateau to a more positive value and increased the force of contraction, whereas benzocaine shortened the action potential and decreased contractile force. In Purkinje fibers, both local an...

BACKGROUND The regulation of contractility of the transplanted heart depends on circulating catecholamines resulting from cardiac denervation. Supersensitivity to circulating catecholamines may result from loss of presynaptic neuronal uptake or upregulation of postsynaptic beta-adrenergic receptors. METHODS AND RESULTS Dose-response curves using the beta-adrenergic receptor agonists isoprenal...

Myocardium to Myocardial Structure in Humans To the Editor: Nagueh and colleagues1 investigated the relationship between myocardial ultrastructure and the inotropic contractile reserve of the hibernating myocardium. They suggested that the amount of interstitial fibrosis in a dysfunctional myocardial segment is an important determinant of both inotropic contractile reserve during dobutamine sti...

Adrenomedullin (ADM) acts as an autocrine or a paracrine factor in the regulation of cardiac function. The intracellular mechanisms involved in the direct effect of ADM on adult rat ventricular myocytes (ARVMs) are still to be elucidated. In ARVMs from normal rats, ADM produced an initial (< 30 min) increase in cell shortening and Ca2+ transients and a marked decrease in both on prolonged incub...

The aim of this study was to examine a possible role for extracellular pyrimidines as inotropic factors for the heart. First, nucleotide plasma levels were measured to evaluate whether UTP is released in patients with coronary heart disease. Then, inotropic effects of pyrimidines were examined in isolated mouse cardiomyocytes. Finally, expression of pyrimidine-selective receptors (a subgroup of...

Background—Contrary to b1and b2-adrenoceptors, b3-adrenoceptors mediate a negative inotropic effect in human ventricular muscle. To assess their functional role in heart failure, our purpose was to compare the expression and contractile effect of b3-adrenoceptors in nonfailing and failing human hearts. Methods and Results—We analyzed left ventricular samples from 29 failing (16 ischemic and 13 ...

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...

In electrically driven left atria isolated from guinea pig and rat, a new milrinone analog, 6-ethyl-5-propionyl-1,2-dihydro-2-oxo-3-pyridine carbonitrile, produced a positive inotropic effect that was not dependent on adrenergic mechanisms and was more marked than that exerted by the parent compound. Its inotropic action was almost completely abolished by pretreatment of atria with adenosine de...

The inotropic responsiveness to adrenergic stimulation is diminished in hypertension associated with left ventricular hypertrophy (LVH). This was shown in hypertrophied hearts from renal hypertensive rats (RHR) (two-kidney, one clip hypertension, Goldblatt) 6 weeks after renal artery clipping when compared to age-matched normotensive sham-operated controls (NR). The isoproterenol-stimulated ino...