Electrophysiologic effects of acute myocardial ischemia: a theoretical study of altered cell excitability and action potential duration
Catherine
Lloyd
Bioengineering Institute, University of Auckland
Model Status
This is the original unchecked version of the model imported from the previous
CellML model repository, 24-Jan-2006.
Model Structure
ABSTRACT: OBJECTIVE: To study the ionic mechanisms of electrophysiologic changes in cell excitability and action potential duration during the acute phase of myocardial ischemia. METHODS: Using an ionic-based theoretical model of the cardiac ventricular cell, the dynamic LRd model, we have simulated the three major component conditions of acute ischemia (elevated [K]o, acidosis and anoxia) at the level of individual ionic currents and ionic concentrations. The conditions were applied individually and in combination to identify ionic mechanisms responsible for reduced excitability at rest potentials, delayed recovery of excitability, and shortened action potential duration. RESULTS: Increased extracellular potassium ([K]o) had the major effect on cell excitability by depolarizing resting membrane potential (Vrest), causing reduction in sodium channel availability. Acidosis caused a [K]o-independent reduction in maximum upstroke velocity, (dVm/dt)max. A transition from sodium-current dominated to calcium-current dominated upstroke occurred, and calcium current alone was able to sustain the upstroke, but only after sodium channels were almost completely (97%) inactivated. Acidic conditions prevented the transition to calcium dominated upstroke by acidic reduction of both sodium and calcium currents. Anoxia, simulated by lowering [ATP]i and activating the APT-dependent potassium current, IK(ATP), was the only process that could decrease action potential duration by more than 50% and reproduce AP shape changes that are observed experimentally. Acidic or anoxic depression of the L-type calcium current could not reproduce the observed action potential shape changes and APD shortening. Delayed recovery of excitability, known as 'post-repolarization refractoriness', was determined by the voltage-dependent kinetics of sodium channel recovery; Vrest depolarization caused by elevated [K]o increased the time constant of (dVm/dt)max recovery from tau = 10.3 ms at [K]o = 4.5 mM to tau = 81.4 ms at [K]o = 12 mM, reflecting major slowing of sodium-channel recovery. Anoxia and acidosis had little affect on tau. CONCLUSIONS: The major conditions of acute ischemia, namely elevated [K]o, acidosis and anoxia, applied at the ionic channel level are sufficient to simulate the major electrical changes associated with ischemia. Depression of membrane excitability and delayed recovery of excitability in the single, unloaded cell are caused by elevated [K]o with additional excitability depression by acidosis. Major changes in action potential duration and shape can only be accounted for by anoxia-dependent opening of IK(ATP).
The original paper reference is cited below:
Electrophysiological effects of acute myocardial ischemia: a theoretical study of altered cell excitability and action potential duration, Robin M. Shaw and Yoram Rudy, 1997, Cardiovascular Research, 35, 256-272. PubMed ID: 9349389
cell diagram of the shaw and viswanathan models showing ionic currents, pumps and exchangers within the sarcolemma and the sarcoplasmic reticulum
A schematic diagram of the Shaw and Rudy 1997 ventricular cell model.
ventricular myocyte
Ventricular Myocyte
electrophysiology
cardiac
cardiac ischemia
ischemia
The University of Auckland
The Bioengineering Institute
2002-04-01
Autumn
Cuellar
A
Yoram
Rudy
c.lloyd@auckland.ac.nz
Changed equation 'i_leak_calcualtion' to 'i_leak_calculation'.
9349389
Added more metadata.
Cardiovascular Research
Catherine
Lloyd
May
1997-08-01
Electrophysiological effects of acute myocardial ischemia: a theoretical study of altered cell excitability and action potential duration
35
256
272
2003-04-09
The University of Auckland, The Bioengineering Institute
2003-07-31
2002-07-18
Robin
Shaw
M
2002-06-17
Catherine
Lloyd
May
Corrected equations.
Added publication date information.
Autumn
Cuellar
A
This is the CellML description of Shaw and Rudy's mathematical model of the electrophysiological effects of acute myocardial ischemia.
Catherine Lloyd
keyword
Catherine
Lloyd
May
The Shaw and Rudy 1997 Model of Electrophysiological Effects of Acute
Myocardial Ischemia.
Ventricular Myocyte
Mammalia