Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
von Lewinski, D; Stumme, B; Fialka, F; Luers, C; Pieske, B.
Functional relevance of the stretch-dependent slow force response in failing human myocardium.
Circ Res. 2004; 94(10):1392-1398
Doi: 10.1161/01.RES.0000129181.48395.ff
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- Führende Autor*innen der Med Uni Graz
- Pieske Burkert Mathias
- von Lewinski Dirk
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- Abstract:
- Stretch induces immediate and delayed inotropic effects in mammalian myocardium via distinct mechanosensitive pathways, but these effects are poorly characterized in human cardiac muscle. We tested the effects of stretch on immediate and delayed force response in failing human myocardium. Experiments were performed in muscle strips from 52 failing human hearts (37 degrees C, 1 Hz, bicarbonate buffer). Muscles were stretched from 88% of optimal length to 98% of optimal length. The resulting immediate and delayed (ie, slow force response [SFR]) increases in twitch force were assessed without and after blockade of the sarcoplasmic reticulum (SR; cyclopiazonic acid and ryanodine), stretch-activated ion channels (SACs; gadolinium, streptomycin), L-type Ca2+-channels (diltiazem), angiotensin II type-1 (AT1) receptors (candesartan), endothelin (ET) receptors (PD145065 or BQ123), Na+/H+ exchange (NHE1; HOE642), or reverse-mode Na+/Ca+ exchange (NCX; KB-R7493). We also tested the effects of stretch on SR Ca2+ load (rapid cooling contractures [RCCs]) and intracellular pH (in BCECF-loaded trabeculae). Stretch induced an immediate (<10 beats), followed by a slow (5 to 10 minutes), force response. Twitch force increased to 232+/-6% of prestretch value during the immediate phase, followed by a further increase to 279+/-8% during the SFR. RCC amplitude significantly increased, but pHi did not change during SFR. Inhibition of SACs, L-type Ca2+ channels, AT1 receptors, or ET receptors did not affect the stretch-dependent immediate or SFR. In contrast, the SFR was reduced by NHE1 inhibition and almost completely abolished by reverse-mode NCX inhibition or blockade of sarcoplasmic reticulum function. The data demonstrate the existence of a functionally relevant, SR-Ca2+-dependent SFR in failing human myocardium, which partly depends on NHE1 and reverse-mode NCX activation.
- Find related publications in this database (using NLM MeSH Indexing)
- Biomechanics -
- Calcium Channels, L-Type - physiology
- Cardiac Output, Low - metabolism
- Cardiomyopathy, Dilated - physiopathology
- Female - physiopathology
- Humans - physiopathology
- Hydrogen-Ion Concentration - physiopathology
- Ion Channels - physiology
- Kinetics - physiology
- Male - physiology
- Middle Aged - physiology
- Myocardial Contraction - physiology
- Myocardial Ischemia - physiopathology
- Receptor, Angiotensin, Type 1 - physiology
- Receptors, Endothelin - antagonists and inhibitors
- Sodium-Calcium Exchanger - physiology
- Sodium-Hydrogen Antiporter - physiology
- Find related publications in this database (Keywords)
- stretch
- human myocardium
- contractile function
- sodium
- calcium