Computational models of the heart and their use in assessing the actions of drugs

被引:61
作者
Noble, Denis [1 ]
机构
[1] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England
基金
英国惠康基金;
关键词
cardiac cell model; cardiac organ model; repolarization; early after-depolarization (EAD); delayed after-depolarization (DAD);
D O I
10.1254/jphs.CR0070042
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Models of cardiac cells are sufficiently well developed to answer questions concerning the actions of drugs on repolarization and the initiation of arrhythmias. These models can be used to characterize drug-receptor action profiles that would be expected to avoid arrhythmia and so help to identify drugs that may be safer. Several examples of such action profiles are presented here, including a recently-developed blocker of persistent sodium current, ranolazine. The models have also been incorporated into tissue and organ models that enable arrhythmia to be modelled also at these levels. Work at these levels can reproduce both re-entrant arrhythmia and fibrillation.
引用
收藏
页码:107 / 117
页数:11
相关论文
共 61 条
[1]   Influence of transmural repolarization gradients on the electrophysiology and pharmacology of ventricular myocardium. Cellular basis for the Brugada and long-QT syndromes [J].
Antzelevitch, C ;
Nesterenko, VV ;
Muzikant, AL ;
Rice, JJ ;
Chen, G ;
Colatsky, T .
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES, 2001, 359 (1783) :1201-1216
[2]   Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazine [J].
Belardinelli, L. ;
Shryock, J. C. ;
Fraser, H. .
HEART, 2006, 92 :6-14
[3]  
BENSON AP, 2006, BIOL SCI
[4]   Preclinical cardiac safety assessment of pharmaceutical compounds using an integrated systems-based computer model of the heart [J].
Bottino, D ;
Penland, RC ;
Stamps, A ;
Traebert, M ;
Dumotier, D ;
Georgieva, A ;
Helmlinger, G ;
Lett, GS .
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, 2006, 90 (1-3) :414-443
[5]   EFFECTS OF REPETITIVE ACTIVITY ON DEVELOPED FORCE AND INTRACELLULAR SODIUM IN ISOLATED SHEEP AND DOG PURKINJE-FIBERS [J].
BOYETT, MR ;
HART, G ;
LEVI, AJ ;
ROBERTS, A .
JOURNAL OF PHYSIOLOGY-LONDON, 1987, 388 :295-322
[6]   Geometric modeling of the human torso using cubic hermite elements [J].
Bradley, CP ;
Pullan, AJ ;
Hunter, PJ .
ANNALS OF BIOMEDICAL ENGINEERING, 1997, 25 (01) :96-111
[7]  
BRIL A, 1995, J PHARMACOL EXP THER, V273, P1264
[8]   Genetic basis and molecular mechanism for idiopathic: ventricular fibrillation [J].
Chen, QY ;
Kirsch, GE ;
Zhang, DM ;
Brugada, R ;
Brugada, J ;
Brugada, P ;
Potenza, D ;
Moya, A ;
Borggrefe, M ;
Breithardt, G ;
Ortiz-Lopez, R ;
Wang, Z ;
Antzelevitch, C ;
O'Brien, RE ;
Schulze-Bahr, E ;
Keating, MT ;
Towbin, JA ;
Wang, Q .
NATURE, 1998, 392 (6673) :293-296
[9]   Linking a genetic defect to its cellular phenotype in a cardiac arrhythmia [J].
Clancy, CE ;
Rudy, Y .
NATURE, 1999, 400 (6744) :566-569
[10]   Electric impedance of the squid giant axon during activity [J].
Cole, KS ;
Curtis, HJ .
JOURNAL OF GENERAL PHYSIOLOGY, 1939, 22 (05) :649-670