Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Bito, V; Heinzel, FR; Weidemann, F; Dommke, C; van der Velden, J; Verbeken, E; Claus, P; Bijnens, B; De Scheerder, I; Stienen, GJ; Sutherland, GR; Sipido, KR.
Cellular mechanisms of contractile dysfunction in hibernating myocardium.
Circ Res. 2004; 94(6):794-801
Doi: 10.1161/01.RES.0000124934.84048.DF
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Heinzel Frank
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Ischemic heart disease is a leading cause of chronic heart failure. Hibernation (ie, a chronic reduction of myocardial contractility distal to a severe coronary stenosis and reversible on revascularization) is an important contributing factor. The underlying cellular mechanisms remain however poorly understood. In young pigs (n=13, ISCH), an acquired coronary stenosis >90% (4 to 6 weeks) resulted in the development of hibernating myocardium. Single cardiac myocytes from the ISCH area were compared with cells from the same area obtained from matched normal pigs (n=12, CTRL). Myocytes from ISCH were larger than from CTRL. In field stimulation, unloaded cell shortening was reduced and slower in ISCH; relaxation was not significantly different. The amplitude of the [Ca2+]i transient was not significantly reduced, but reducing [Ca2+]o for CTRL cells could mimic the properties of ISCH, inducing a significant reduction of contraction, but not of [Ca2+]i. Action potentials were longer in ISCH. With square voltage-clamp pulses of equal duration in ISCH and CTRL, the amplitude of the [Ca2+]i transient was significantly smaller in ISCH, as was the Ca2+ current. Near-maximal activation of the myofilaments resulted in smaller contractions of ISCH than of CTRL cells. There was no evidence for increased degradation of Troponin I. In conclusion, cellular remodeling is a major factor in the contractile dysfunction of the hibernating myocardium. Myocytes are hypertrophied, action potentials are prolonged, and L-type Ca2+ currents and Ca2+ release are decreased. The steep [Ca2+]i dependence of contraction and possibly a reduction of maximal myofilament responsiveness further enhance the contractile deficit.
- Find related publications in this database (using NLM MeSH Indexing)
- Action Potentials -
- Animals -
- Calcium Channels, L-Type - drug effects
- Calcium Signaling - drug effects
- Cell Size - drug effects
- Coronary Stenosis - complications
- Hypertrophy - complications
- Ion Transport - drug effects
- Microfilaments - physiology
- Myocardial Contraction - physiology
- Myocardial Stunning - etiology
- Myocardium - pathology
- Myocytes, Cardiac - pathology
- Nifedipine - pharmacology
- Patch-Clamp Techniques - pharmacology
- Swine - pharmacology
- Troponin I - metabolism
- Find related publications in this database (Keywords)
- ischemia
- hibernation
- myocytes
- ion channels
- Ca2+ current