Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
von Lewinski, D; Kockskamper, J; Zhu, D; Post, H; Elgner, A; Pieske, B.
Reduced Stretch-Induced Force Response in Failing Human Myocardium Caused by Impaired Na+-Contraction Coupling
CIRC-HEART FAIL. 2009; 2(1): 47-55.
Doi: 10.1161/CIRCHEARTFAILURE.108.794065
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- Führende Autor*innen der Med Uni Graz
- von Lewinski Dirk
- Co-Autor*innen der Med Uni Graz
- Kockskämper Jens
- Pieske Burkert Mathias
- Post Heiner
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- Abstract:
- Background-Stretch elicits an immediate, followed by a delayed, inotropic response in various animal models and failing human myocardium. This study aimed to characterize functional differences in the stretch response between failing and nonfailing human myocardium. Methods and Results-Experiments were performed in muscle tissue from 86 failing and 16 nonfailing human hearts. Muscles were stretched from 88% to 98% of optimal length. Resulting immediate (Frank-Starling mechanism [FSM]) and delayed (slow-force response [SFR]) increases in twitch force were assessed before and after blockade of nitric oxide synthase, phosphatidylinositol-3-kinase, or reverse-mode Na+/Ca2+ exchange. Stretch-induced changes in [Na+](i) were measured using fluorescent indicator sodium-binding benzofuran isophthalate-AM. Nitric oxide synthase isoform expression was quantified by Western blot analysis. FSM was comparable between nonfailing (227 +/- 8%) and failing (222 +/- 9%) myocardium, whereas the additional increase during SFR (approximate to 5 minutes) was larger in nonfailing myocardium (to 126 +/- 3% versus 119 +/- 2% of force of FSM, respectively; P<0.05). Basal [Na+](i) and stretch-induced increase in [Na+](i) were lower in nonfailing myocardium. Inhibition of the Na+/H+ exchange largely reduced the increase in [Na+](i) and significantly blocked the SFR. In both groups, SFR was almost completely prevented by reverse-mode Na+/Ca+-exchanger inhibition. Although neuronal and inducible nitric oxide synthase expression were significantly upregulated in failing myocardium, inhibition of nitric oxide synthase and phosphatidylinositol-3-kinase had no effect on FSM or SFR. Conclusions-These data demonstrate a Na+-independent FSM and a Na+-dependent SFR in both nonfailing and failing human myocardium. The larger stretch-dependent increase in [Na+](i) in failing myocardium was associated with a blunted functional response, indicating impaired Na+-contraction coupling in the failing human heart. (Circ Heart Fail. 2009;2:47-55.)
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Blotting, Western -
- Enzyme Inhibitors - pharmacology
- Heart Failure - metabolism Heart Failure - physiopathology
- Humans -
- Middle Aged -
- Muscle Contraction - physiology
- Myocardial Contraction - drug effects Myocardial Contraction - physiology
- Myocardium - metabolism Myocardium - pathology
- NG-Nitroarginine Methyl Ester - pharmacology
- Nitric Oxide Synthase - biosynthesis
- Reflex, Stretch - physiology
- Signal Transduction - drug effects
- Sodium - metabolism
- Sodium-Calcium Exchanger - antagonists and inhibitors Sodium-Calcium Exchanger - metabolism
- Find related publications in this database (Keywords)
- contractility
- heart failure
- myocardial contraction
- physiology