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There is no direct evidence to indicate that pump dysfunction in a dilated chamber reflects the impact of chamber dilatation rather than the degree of intrinsic systolic failure resulting from myocardial damage. In the present study, we explored the relative roles of intrinsic myocardial systolic dysfunction and chamber dilatation as mediators of left(More)
Despite reductions in beta-adrenoreceptor (beta-AR)-mediated inotropic effects induced by sustained sympathetic activation in cardiac disease, whether these changes necessarily result in reductions in systolic function under resting conditions (baseline function) is not clear. Moreover, possible compensatory mechanisms which might contribute to maintaining(More)
We sought to explore the distribution pattern of Na(+) channels across ventricular wall, and to determine its functional correlates, in the guinea pig heart. Voltage-dependent Na(+) channel (Na(v)) protein expression levels were measured in transmural samples of ventricular tissue by Western blotting. Isolated, perfused heart preparations were used to(More)
Phosphodiesterase (PDE) inhibitors are potent cardiotonic agents used for parenteral inotropic support in heart failure. Contractile effects of these agents are mediated through cAMP-protein kinase A-induced stimulation of I Ca2+ which ultimately results in increased Ca2+-induced sarcoplasmic reticulum Ca2+ release. A number of additional effects such as(More)
The transition from compensated to decompensated left ventricular hypertrophy (LVH) in hypertension involves excessive beta-adrenoreceptor (beta-AR) stimulation. To explore whether aldosterone receptor activation contributes toward beta-AR-induced left ventricular (LV) decompensation in hypertensive LVH, the effect of spironolactone (SPIRO; 80 mg x kg(-1) x(More)
Activation of the large-conductance Ca2+-activated K+ channel (BK) in the cardiac inner mitochondrial membrane has been suggested to protect the heart against ischemic injury. However, these findings are limited by the low selectivity profile and potency of the BK channel activator (NS1619) used. In the present study, we address the cardioprotective role of(More)
Widely used murine models of adrenergic-induced cardiomyopathy offer little insight into electrical derangements seen in human heart failure owing to profound differences in the characteristics of ventricular repolarization in mice and rats compared with humans. We therefore sought to determine whether sustained adrenergic activation may produce a(More)
Hypokalemia is a common biochemical finding in cardiac patients and may represent a side effect of diuretic therapy or result from endogenous activation of renin-angiotensin system and high adrenergic tone. Hypokalemia is independent risk factor contributing to reduced survival of cardiac patients and increased incidence of arrhythmic death. Animal studies(More)
Dofetilide is class III antiarrhythmic agent which prolongs cardiac action potential duration because of selective inhibition of I Kr, the rapid component of the delayed rectifier K+ current. Although clinical studies reported on proarrhythmic risk associated with dofetilide treatment, the contributing electrophysiological mechanisms remain poorly(More)
In the present study we sought to determine whether reduced contractile responses to phosphodiesterase inhibitors occur in the face of chronic cardiac hypertrophy associated with beta-adrenergic inotropic downregulation. As compared to age-matched Wistar-Kyoto control rats, spontaneously hypertensive rats at 6-8 months of age exhibited a striking decrease(More)