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(Circulation. 2008;118:1202-1211.)
© 2008 American Heart Association, Inc.

Special Report

Systems Approach to Understanding Electromechanical Activity in the Human Heart

A National Heart, Lung, and Blood Institute Workshop Summary

Yoram Rudy, PhD; Michael J. Ackerman, MD, PhD; Donald M. Bers, PhD; Colleen E. Clancy, PhD; Steven R. Houser, PhD; Barry London, MD, PhD; Andrew D. McCulloch, PhD; Dennis A. Przywara, PhD; Randall L. Rasmusson, PhD; R. John Solaro, PhD; Natalia A. Trayanova, PhD; David R. Van Wagoner, PhD; András Varró, MD, PhD, DSc; James N. Weiss, MD; David A. Lathrop, PhD

From the Departments of Biomedical Engineering, Cell Biology and Physiology, Medicine, Radiology, and Pediatrics and the Cardiac Bioelectricity and Arrhythmia Center, Washington University, St Louis, Mo (Y.R.); Departments of Medicine, Pediatrics, Molecular Pharmacology, and Experimental Therapeutics, Mayo Clinic, Rochester, Minn (M.J.A.); Department of Pharmacology, University of California, Davis (D.M.B.); Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY (C.E.C.); Department of Physiology, Temple University School of Medicine, Philadelphia, Pa (S.R.H.); Cardiovascular Institute, University of Pittsburgh, Pittsburgh, Pa (B.L.); Bioengineering Department, University of California, San Diego, La Jolla (A.D.M.); Division of Cardiovascular Diseases, National, Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md (D.A.P., D.A.L.); Department of Physiology and Biophysics, State Universities of New York at Buffalo (R.L.R.); Department of Physiology and Biophysics, and Center for Cardiovascular Research, University of Illinois at Chicago (R.J.S.); Biomedical Engineering, Johns Hopkins University, Baltimore, Md (N.A.T.); Departments of Molecular Cardiology and Molecular Medicine, Cleveland Clinic Lerner College of Medicine–CWRU, Cleveland, Ohio (D.R.V.W.); Department of Pharmacology and Pharmacotherapy, University of Szeged, and Division for Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary (A.V.); and Division of Cardiology, University of California, Los Angeles (J.N.W.).

Correspondence to Yoram Rudy, PhD, Director, Cardiac Bioelectricity and Arrhythmia Center, The Fred Saigh Distinguished Professor, Washington University, Campus Box 1097, Whitaker Hall Room 290B, One Brookings Dr, St Louis, MO 63130-4899. E-mail rudy{at}wustl.edu

The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of cardiologists, cardiac electrophysiologists, cell biophysicists, and computational modelers on August 20 and 21, 2007, in Washington, DC, to advise the NHLBI on new research directions needed to develop integrative approaches to elucidate human cardiac function. The workshop strove to identify limitations in the use of data from nonhuman animal species for elucidation of human electromechanical function/activity and to identify what specific information on ion channel kinetics, calcium handling, and dynamic changes in the intracellular/extracellular milieu is needed from human cardiac tissues to develop more robust computational models of human cardiac electromechanical activity. This article summarizes the workshop discussions and recommendations on the following topics: (1) limitations of animal models and differences from human electrophysiology, (2) modeling ion channel structure/function in the context of whole-cell electrophysiology, (3) excitation–contraction coupling and regulatory pathways, (4) whole-heart simulations of human electromechanical activity, and (5) what human data are currently needed and how to obtain them. The recommendations can be found on the NHLBI Web site at http://www.nhlbi.nih.gov/meetings/workshops/electro.htm.

Key Words: arrhythmia • cardiovascular diseases • contractility • electrophysiology • mechanics

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