Published online before print March 4, 2004, doi: 10.1161/01.RES.0000124934.84048.DF
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on October 7, 2003
Revised on February 18, 2004
Accepted on February 20, 2004
Cellular Mechanisms of Contractile Dysfunction in Hibernating Myocardium
Virginie Bito ;
From the Laboratories of Experimental Cardiology (V.B., F.R.H., I.D.S., K.R.S.), Cardiac Imaging (F.W., C.D., P.C., B.B., G.R.S.), and Pathology (E.V.), University of Leuven, Leuven, Belgium; Laboratory for Physiology (J.v.d.V., G.J.M.S.), VU University Medical Center, Amsterdam, the Netherlands; Institute of Pathophysiology (F.R.H.), University of Essen, Essen, Germany.
* To whom correspondence should be addressed. E-mail: Karin.Sipido{at}med.kuleuven.ac.be.
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.
Key words: ischemia • hibernation • myocytes • ion channels • Ca2+ current
This article has been cited by other articles:
 |
|
 |
|
  W. Streb, M. Marciniak, P. Claus, A. Marciniak, M. McLaughlin, J. D'hooge, F. E. Rademakers, B. Bijnens, and G. R. Sutherland Full or pressure limited reperfusion of an acute myocardial infarct results in a different wall thickness and deformation of the distal myocardium - implications for clinical reperfusion strategies Eur J Echocardiogr, July 1, 2008; 9(4): 458 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J.J.M. Brundel, L. Ke, A.-J. Dijkhuis, X. Qi, A. Shiroshita-Takeshita, S. Nattel, R. H. Henning, and H. H. Kampinga Heat shock proteins as molecular targets for intervention in atrial fibrillation Cardiovasc Res, June 1, 2008; 78(3): 422 - 428. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. R. Heinzel, V. Bito, L. Biesmans, M. Wu, E. Detre, F. von Wegner, P. Claus, S. Dymarkowski, F. Maes, J. Bogaert, et al. Remodeling of T-Tubules and Reduced Synchrony of Ca2+ Release in Myocytes From Chronically Ischemic Myocardium Circ. Res., February 15, 2008; 102(3): 338 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Bijnens, P. Claus, F. Weidemann, J. Strotmann, and G. R. Sutherland Investigating Cardiac Function Using Motion and Deformation Analysis in the Setting of Coronary Artery Disease Circulation, November 20, 2007; 116(21): 2453 - 2464. [Full Text] [PDF]
|
|
|
|
|
|
V. Bito, J. van der Velden, P. Claus, C. Dommke, A. Van Lommel, L. Mortelmans, E. Verbeken, B. Bijnens, G. Stienen, and K. R. Sipido Reduced Force Generating Capacity in Myocytes From Chronically Ischemic, Hibernating Myocardium Circ. Res., February 2, 2007; 100(2): 229 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shah, F. G. Akar, and G. F. Tomaselli Molecular Basis of Arrhythmias Circulation, October 18, 2005; 112(16): 2517 - 2529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Ovchinnikov, G. Suzuki, J. M. Canty Jr., and J. A. Fallavollita Blunted functional responses to pre- and postjunctional sympathetic stimulation in hibernating myocardium Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1719 - H1728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Heusch, R. Schulz, and S. H. Rahimtoola Myocardial hibernation: a delicate balance Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H984 - H999. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. Sutherland Do regional deformation indexes reflect regional perfusion in all ischemic substrates? J. Am. Coll. Cardiol., October 19, 2004; 44(8): 1672 - 1674. [Full Text] [PDF]
|
|
|
|
|
|
G. F. Tomaselli and D. P. Zipes What Causes Sudden Death in Heart Failure? Circ. Res., October 15, 2004; 95(8): 754 - 763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Heusch and K. R. Sipido Myocardial Hibernation: A Double-Edged Sword Circ. Res., April 30, 2004; 94(8): 1005 - 1007. [Full Text] [PDF]
|
|