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Positive inotropic effects of the novel Na+-channel modulator BDF 9198 in human nonfailing and failing myocardium.
- Source :
-
Journal of cardiovascular pharmacology [J Cardiovasc Pharmacol] 1998 May; Vol. 31 (5), pp. 684-9. - Publication Year :
- 1998
-
Abstract
- The aim of this study was to investigate the inotropic properties of the novel Na+-channel modulator BDF 9198 in human nonfailing and failing myocardium. For comparison the Na+-channel modulator BDF 9148, the beta-adrenoceptor-agonist isoprenaline, and calcium were studied. Concentration-response curves for BDF 9198 (0.01-30 microM), BDF 9148 (0.01-30 microM), isoprenaline (0.001-1 microM), and calcium (1.8-15 mM) were obtained in electrically driven left ventricular human papillary muscle strips (1 Hz, 37 degrees C; dilated cardiomyopathy, NYHA IV, heart transplantation; nonfailing, donor hearts). Whereas isoprenaline was significantly less effective and less potent in increasing the force of contraction in failing human myocardium than in nonfailing myocardium (p < 0.01), BDF 9198 and BDF 9148 were (in NYHA IV) as effective as in nonfailing human tissue. In both tissues, BDF 9198 and BDF 9148 exerted similar positive inotropic effects as calcium, with the novel Na+-channel modulator BDF 9198 being more potent in increasing force of contraction than was the preceding agent BDF 9148. The potencies of both Na+-channel modulators, BDF 9198 and BDF 9148, were enhanced in human failing myocardium when compared with nonfailing myocardium. In summary, the novel Na+-channel modulator BDF 9198 increases force of contraction to the same extent as calcium and with a higher potency than BDF 9148. The sensitivity of failing human myocardium to Na+-channel modulators is increased when compared with nonfailing myocardium, which might be the result of an altered Na+ homeostasis in human heart failure.
- Subjects :
- Azetidines pharmacology
Cell Membrane drug effects
Cell Membrane metabolism
Electric Stimulation
Heart physiology
Humans
Isoproterenol pharmacology
Myocardium metabolism
Papillary Muscles drug effects
Papillary Muscles physiology
Receptors, Adrenergic, beta metabolism
Ventricular Function, Left drug effects
Cardiotonic Agents pharmacology
Heart drug effects
Heart Failure physiopathology
Myocardial Contraction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0160-2446
- Volume :
- 31
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of cardiovascular pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 9593067
- Full Text :
- https://doi.org/10.1097/00005344-199805000-00006