Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Maier, LS; Schwan, C; Schillinger, W; Minami, K; Schütt, U; Pieske, B.
Gingerol, isoproterenol and ouabain normalize impaired post-rest behavior but not force-frequency relation in failing human myocardium.
Cardiovasc Res. 2000; 45(4):913-924
Doi: 10.1016/S0008-6363(99)00387-9
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- Führende Autor*innen der Med Uni Graz
- Pieske Burkert Mathias
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- Abstract:
- OBJECTIVE: Rest- and stimulation frequency-dependent potentiation of contractile force is blunted in failing human myocardium. These alterations have been related to reduced sarcoplasmic reticulum (SR) Ca(2+)-reuptake and enhanced transsarcolemmal Ca(2+)-elimination by Na+/Ca(2+)-exchange. We investigated whether inotropic interventions that enhance SR Ca(2+)-uptake, or reduce Ca(2+)-elimination by Na+/Ca(2+)-exchange, normalize impaired post-rest and force-frequency behavior in left ventricular muscle strips from failing human hearts. METHODS: We tested the influence of [10]-gingerol which activates SR Ca(2+)-ATPase (10 mumol/l; n = 13), and isoproterenol which activates cAMP-dependent pathways (0.01, 0.1, 1 mumol/l; n = 40) on post-rest and force-frequency behavior. Ouabain which blocks Na+/K(+)-ATPase (0.03 mumol/l; n = 16) was used to test the effects of inhibiting Ca(2+)-elimination by Na+/Ca(2+)-exchange. For comparison, the effects of blocking SR Ca(2+)-uptake by thapsigargin (10 mumol/l; n = 14) were tested. In addition, Ca(2+)-uptake in myocardial homogenates was measured for gingerol (10 mumol/l; n = 6). RESULTS: Gingerol, isoproterenol (0.1, 1 mumol/l) and ouabain exerted significant positive inotropic effects under basal experimental conditions and normalized post-rest behavior. In contrast, force-frequency relation was only slightly improved by gingerol and isoproterenol (0.01 mumol/l). Ouabain and isoproterenol (1 mumol/l) further deteriorated force-frequency relation due to frequency-dependent significant increases in diastolic tension. Thapsigargin exerted negative inotropic effects and significantly deteriorated post-rest and force-frequency behavior. In addition, gingerol increased SR Ca(2+)-uptake significantly in myocardial homogenates. CONCLUSIONS: Inotropic interventions that stimulate SR Ca(2+)-ATPase or inhibit Na+/Ca(2+)-exchange normalize impaired post-rest behavior. Force-frequency behavior is only slightly improved by stimulation of SR Ca(2+)-ATPase but not by inhibition of Na+/Ca(2+)-exchange. This dissociation between post-rest and force-frequency behavior results from diastolic dysfunction at high stimulation rates.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Analysis of Variance -
- Calcium - metabolism
- Calcium-Transporting ATPases - metabolism
- Cardiotonic Agents - pharmacology
- Cyclic AMP - metabolism
- Enzyme Inhibitors - pharmacology
- Fatty Alcohols - pharmacology
- Heart Failure, Congestive - metabolism
- Humans - metabolism
- Isoproterenol - pharmacology
- Middle Aged - pharmacology
- Myocardial Contraction - drug effects
- Myocardium - metabolism
- Na(+)-K(+)-Exchanging ATPase - antagonists and inhibitors
- Ouabain - pharmacology
- Sarcoplasmic Reticulum - drug effects
- Stimulation, Chemical - drug effects
- Thapsigargin - pharmacology
- Find related publications in this database (Keywords)
- contractile function
- E-C coupling
- heart failure
- inotropic agents