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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hussain, Rizwan I. Galindo-tovar, Alejandro Levy, Finn Olav Ravens, Ursula Krobert, Kurt A. Chen, Lu Kaumann, Alberto J. Christ, Torsten Molenaar, Peter Engel, Andreas Berk, Emanuel Gillette, Katherine T. |
| Description | Author Affiliation: Molenaar P ( Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.) |
| Abstract | BACKGROUND AND PURPOSE: PDE3 and/or PDE4 control ventricular effects of catecholamines in several species but their relative effects in failing human ventricle are unknown. We investigated whether the PDE3-selective inhibitor cilostamide (0.3-1 µM) or PDE4 inhibitor rolipram (1-10 µM) modified the positive inotropic and lusitropic effects of catecholamines in human failing myocardium. EXPERIMENTAL APPROACH: Right and left ventricular trabeculae from freshly explanted hearts of 5 non-ß-blocker-treated and 15 metoprolol-treated patients with terminal heart failure were paced to contract at 1 Hz. The effects of (-)-noradrenaline, mediated through ß1 adrenoceptors (ß2 adrenoceptors blocked with ICI118551), and (-)-adrenaline, mediated through ß2 adrenoceptors (ß1 adrenoceptors blocked with CGP20712A), were assessed in the absence and presence of PDE inhibitors. Catecholamine potencies were estimated from -logEC50s. KEY RESULTS: Cilostamide did not significantly potentiate the inotropic effects of the catecholamines in non-ß-blocker-treated patients. Cilostamide caused greater potentiation (P = 0.037) of the positive inotropic effects of (-)-adrenaline (0.78 ± 0.12 log units) than (-)-noradrenaline (0.47 ± 0.12 log units) in metoprolol-treated patients. Lusitropic effects of the catecholamines were also potentiated by cilostamide. Rolipram did not affect the inotropic and lusitropic potencies of (-)-noradrenaline or (-)-adrenaline on right and left ventricular trabeculae from metoprolol-treated patients. CONCLUSIONS AND IMPLICATIONS: Metoprolol induces a control by PDE3 of ventricular effects mediated through both ß1 and ß2 adrenoceptors, thereby further reducing sympathetic cardiostimulation in patients with terminal heart failure. Concurrent therapy with a PDE3 blocker and metoprolol could conceivably facilitate cardiostimulation evoked by adrenaline through ß2 adrenoceptors. PDE4 does not appear to reduce inotropic and lusitropic effects of catecholamines in failing human ventricle. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 3 |
| Volume Number | 169 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2013-06-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Adrenergic Beta-1 Receptor Antagonists Adverse Effects Cyclic Nucleotide Phosphodiesterases, Type 3 Metabolism Heart Failure Drug Therapy Heart Ventricles Drug Effects Metoprolol Receptors, Adrenergic, Beta-1 Receptors, Adrenergic, Beta-2 Adrenergic Alpha-Agonists Chemistry Pharmacology Therapeutic Use Adrenergic Beta-2 Receptor Antagonists Adrenergic Beta-Agonists Anti-Arrhythmia Agents Cardiotonic Agents Cyclic Nucleotide Phosphodiesterases, Type 4 Drug Resistance Epinephrine Agonists Physiopathology Surgery Heart Transplantation In Vitro Techniques Myocardial Contraction Norepinephrine Phosphodiesterase 3 Inhibitors Phosphodiesterase 4 Inhibitors Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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