In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 94, No. 6 ( 2004-04-02), p. 794-801
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 [Ca 2+ ] i transient was not significantly reduced, but reducing [Ca 2+ ] o for CTRL cells could mimic the properties of ISCH, inducing a significant reduction of contraction, but not of [Ca 2+ ] i . Action potentials were longer in ISCH. With square voltage-clamp pulses of equal duration in ISCH and CTRL, the amplitude of the [Ca 2+ ] i transient was significantly smaller in ISCH, as was the Ca 2+ 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 Ca 2+ currents and Ca 2+ release are decreased. The steep [Ca 2+ ] i dependence of contraction and possibly a reduction of maximal myofilament responsiveness further enhance the contractile deficit.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/01.RES.0000124934.84048.DF
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2004
detail.hit.zdb_id:
1467838-X
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