@Article{RSM:Sta95,
  author =       "C.F. Starmer and D.N. Romashko and R.S. Reddy and Y.I.
                 Zilberter and J. Starobin and A.O. Grant and V.I.
                 Krinsky",
  title =        "Proarrhythmic response to potassium channel blockade.
                 Numerical studies of polymorphic tachyarrhythmias.",
  journal =      j-C,
  year =         "1995",
  month =        aug,
  volume =       "92",
  number =       "3",
  pages =        "595--605",
  robnote =      "BACKGROUND: Prompted by the results of CAST results,
                 attention has shifted from class I agents that
                 primarily block sodium channels to class III agents
                 that primarily block potassium channels for
                 pharmacological management of certain cardiac
                 arrhythmias. Recent studies demonstrated that sodium
                 channel blockade, while antiarrhythmic at the cellular
                 level, was inherently proarrhythmic in the setting of a
                 propagating wave front as a result of prolongation of
                 the vulnerable period during which premature
                 stimulation can initiate reentrant activation. From a
                 theoretical perspective, sodium (depolarizing) and
                 potassium (repolarizing) currents are complementary so
                 that if antiarrhythmic and proarrhythmic properties are
                 coupled to modulation of sodium currents, then
                 antiarrhythmic and proarrhythmic properties might
                 similarly be coupled to modulation of potassium
                 currents. The purpose of the present study was to
                 explore the role of repolarization currents during
                 reentrant excitation. METHODS AND RESULTS: To assess
                 the generic role of repolarizing currents during
                 reentry, we studied the responses of a two-dimensional
                 array of identical excitable cells based on the
                 FitzHugh-Nagumo model, consisting of a single
                 excitation (sodium-like) current and a single recovery
                 (potassium-like) current. Spiral wave reentry was
                 initiated by use of S1S2 stimulation, with the delay
                 timed to occur within the vulnerable period (VP). While
                 holding the sodium conductance constant, the potassium
                 conductance (gK) was reduced from 1.13 to 0.70
                 (arbitrary units), producing a prolongation of the
                 action potential duration (APD). When gK was 1.13, the
                 tip of the spiral wave rotated around a small,
                 stationary, unexcited region and the computed ECG was
                 monomorphic. As gK was reduced, the APD was prolonged
                 and the unexcited region became mobile (nonstationary),
                 such that the tip of the spiral wave inscribed an
                 outline similar to a multipetaled flower;
                 concomitantly, the computed ECG became progressively
                 more polymorphic. The degree of polymorphism was
                 related to the APD and the configuration of the
                 nonstationary spiral core. CONCLUSIONS: Torsadelike
                 (polymorphic) ECGs can be derived from spiral wave
                 reentry in a medium of identical cells. Under normal
                 conditions, the spiral core around which a reentrant
                 wave front rotates is stationary. As the balance of
                 repolarizing currents becomes less outward (eg,
                 secondary to potassium channel blockade), the APD is
                 prolonged. When the wavelength (APD.velocity) exceeds
                 the perimeter of the stationary unexcited core, the
                 core will become unstable, causing spiral core drift.
                 Large repolarizing currents shorten the APD and result
                 in a monomorphic reentrant process (stationary core),
                 whereas smaller currents prolong the APD and amplify
                 spiral core instability, resulting in a polymorphic
                 process. We conclude that, similar to sodium channel
                 blockade, the proarrhythmic potential of potassium
                 channel blockade in the setting of propagation may be
                 directly linked to its cellular antiarrhythmic
                 potential, ie, arrhythmia suppression resulting from a
                 prolonged APD may, on initiation of a reentrant wave
                 front, destabilize the core of a rotating spiral,
                 resulting in complex motion (precession) of the spiral
                 tip around a nonstationary region of unexcited cells.
                 In tissue with inhomogeneities, core instability alters
                 the activation sequence from one reentry cycle to the
                 next and can lead to spiral wave fractination as the
                 wave front collides with inhomogeneous regions.
                 Depending on the nature of the inhomogeneities, wave
                 front fragments may annihilate one another, producing a
                 nonsustained arrhythmia, or may spawn new spirals
                 (multiple wavelets), producing fibrillation and sudden
                 cardiac death.",
  bibdate =      "Mon Jan 8 18:24:04 2007",
}

{"_id":"ZCxjy8fxDR5uez8gg","bibbaseid":"starmer-romashko-reddy-zilberter-starobin-grant-krinsky-proarrhythmicresponsetopotassiumchannelblockadenumericalstudiesofpolymorphictachyarrhythmias-1995","downloads":0,"creationDate":"2016-07-01T21:38:41.312Z","title":"Proarrhythmic response to potassium channel blockade. Numerical studies of polymorphic tachyarrhythmias.","author_short":["Starmer, C.","Romashko, D.","Reddy, R.","Zilberter, Y.","Starobin, J.","Grant, A.","Krinsky, V."],"year":1995,"bibtype":"article","biburl":"http://www.sci.utah.edu/~macleod/Bibtex/biglit.bib","bibdata":{"bibtype":"article","type":"article","author":[{"firstnames":["C.F."],"propositions":[],"lastnames":["Starmer"],"suffixes":[]},{"firstnames":["D.N."],"propositions":[],"lastnames":["Romashko"],"suffixes":[]},{"firstnames":["R.S."],"propositions":[],"lastnames":["Reddy"],"suffixes":[]},{"firstnames":["Y.I."],"propositions":[],"lastnames":["Zilberter"],"suffixes":[]},{"firstnames":["J."],"propositions":[],"lastnames":["Starobin"],"suffixes":[]},{"firstnames":["A.O."],"propositions":[],"lastnames":["Grant"],"suffixes":[]},{"firstnames":["V.I."],"propositions":[],"lastnames":["Krinsky"],"suffixes":[]}],"title":"Proarrhythmic response to potassium channel blockade. Numerical studies of polymorphic tachyarrhythmias.","journal":"j-C","year":"1995","month":"August","volume":"92","number":"3","pages":"595–605","robnote":"BACKGROUND: Prompted by the results of CAST results, attention has shifted from class I agents that primarily block sodium channels to class III agents that primarily block potassium channels for pharmacological management of certain cardiac arrhythmias. Recent studies demonstrated that sodium channel blockade, while antiarrhythmic at the cellular level, was inherently proarrhythmic in the setting of a propagating wave front as a result of prolongation of the vulnerable period during which premature stimulation can initiate reentrant activation. From a theoretical perspective, sodium (depolarizing) and potassium (repolarizing) currents are complementary so that if antiarrhythmic and proarrhythmic properties are coupled to modulation of sodium currents, then antiarrhythmic and proarrhythmic properties might similarly be coupled to modulation of potassium currents. The purpose of the present study was to explore the role of repolarization currents during reentrant excitation. METHODS AND RESULTS: To assess the generic role of repolarizing currents during reentry, we studied the responses of a two-dimensional array of identical excitable cells based on the FitzHugh-Nagumo model, consisting of a single excitation (sodium-like) current and a single recovery (potassium-like) current. Spiral wave reentry was initiated by use of S1S2 stimulation, with the delay timed to occur within the vulnerable period (VP). While holding the sodium conductance constant, the potassium conductance (gK) was reduced from 1.13 to 0.70 (arbitrary units), producing a prolongation of the action potential duration (APD). When gK was 1.13, the tip of the spiral wave rotated around a small, stationary, unexcited region and the computed ECG was monomorphic. As gK was reduced, the APD was prolonged and the unexcited region became mobile (nonstationary), such that the tip of the spiral wave inscribed an outline similar to a multipetaled flower; concomitantly, the computed ECG became progressively more polymorphic. The degree of polymorphism was related to the APD and the configuration of the nonstationary spiral core. CONCLUSIONS: Torsadelike (polymorphic) ECGs can be derived from spiral wave reentry in a medium of identical cells. Under normal conditions, the spiral core around which a reentrant wave front rotates is stationary. As the balance of repolarizing currents becomes less outward (eg, secondary to potassium channel blockade), the APD is prolonged. When the wavelength (APD.velocity) exceeds the perimeter of the stationary unexcited core, the core will become unstable, causing spiral core drift. Large repolarizing currents shorten the APD and result in a monomorphic reentrant process (stationary core), whereas smaller currents prolong the APD and amplify spiral core instability, resulting in a polymorphic process. We conclude that, similar to sodium channel blockade, the proarrhythmic potential of potassium channel blockade in the setting of propagation may be directly linked to its cellular antiarrhythmic potential, ie, arrhythmia suppression resulting from a prolonged APD may, on initiation of a reentrant wave front, destabilize the core of a rotating spiral, resulting in complex motion (precession) of the spiral tip around a nonstationary region of unexcited cells. In tissue with inhomogeneities, core instability alters the activation sequence from one reentry cycle to the next and can lead to spiral wave fractination as the wave front collides with inhomogeneous regions. Depending on the nature of the inhomogeneities, wave front fragments may annihilate one another, producing a nonsustained arrhythmia, or may spawn new spirals (multiple wavelets), producing fibrillation and sudden cardiac death.","bibdate":"Mon Jan 8 18:24:04 2007","bibtex":"@Article{RSM:Sta95,\n author = \"C.F. Starmer and D.N. Romashko and R.S. Reddy and Y.I.\n Zilberter and J. Starobin and A.O. Grant and V.I.\n Krinsky\",\n title = \"Proarrhythmic response to potassium channel blockade.\n Numerical studies of polymorphic tachyarrhythmias.\",\n journal = j-C,\n year = \"1995\",\n month = aug,\n volume = \"92\",\n number = \"3\",\n pages = \"595--605\",\n robnote = \"BACKGROUND: Prompted by the results of CAST results,\n attention has shifted from class I agents that\n primarily block sodium channels to class III agents\n that primarily block potassium channels for\n pharmacological management of certain cardiac\n arrhythmias. Recent studies demonstrated that sodium\n channel blockade, while antiarrhythmic at the cellular\n level, was inherently proarrhythmic in the setting of a\n propagating wave front as a result of prolongation of\n the vulnerable period during which premature\n stimulation can initiate reentrant activation. From a\n theoretical perspective, sodium (depolarizing) and\n potassium (repolarizing) currents are complementary so\n that if antiarrhythmic and proarrhythmic properties are\n coupled to modulation of sodium currents, then\n antiarrhythmic and proarrhythmic properties might\n similarly be coupled to modulation of potassium\n currents. The purpose of the present study was to\n explore the role of repolarization currents during\n reentrant excitation. METHODS AND RESULTS: To assess\n the generic role of repolarizing currents during\n reentry, we studied the responses of a two-dimensional\n array of identical excitable cells based on the\n FitzHugh-Nagumo model, consisting of a single\n excitation (sodium-like) current and a single recovery\n (potassium-like) current. Spiral wave reentry was\n initiated by use of S1S2 stimulation, with the delay\n timed to occur within the vulnerable period (VP). While\n holding the sodium conductance constant, the potassium\n conductance (gK) was reduced from 1.13 to 0.70\n (arbitrary units), producing a prolongation of the\n action potential duration (APD). When gK was 1.13, the\n tip of the spiral wave rotated around a small,\n stationary, unexcited region and the computed ECG was\n monomorphic. As gK was reduced, the APD was prolonged\n and the unexcited region became mobile (nonstationary),\n such that the tip of the spiral wave inscribed an\n outline similar to a multipetaled flower;\n concomitantly, the computed ECG became progressively\n more polymorphic. The degree of polymorphism was\n related to the APD and the configuration of the\n nonstationary spiral core. CONCLUSIONS: Torsadelike\n (polymorphic) ECGs can be derived from spiral wave\n reentry in a medium of identical cells. Under normal\n conditions, the spiral core around which a reentrant\n wave front rotates is stationary. As the balance of\n repolarizing currents becomes less outward (eg,\n secondary to potassium channel blockade), the APD is\n prolonged. When the wavelength (APD.velocity) exceeds\n the perimeter of the stationary unexcited core, the\n core will become unstable, causing spiral core drift.\n Large repolarizing currents shorten the APD and result\n in a monomorphic reentrant process (stationary core),\n whereas smaller currents prolong the APD and amplify\n spiral core instability, resulting in a polymorphic\n process. We conclude that, similar to sodium channel\n blockade, the proarrhythmic potential of potassium\n channel blockade in the setting of propagation may be\n directly linked to its cellular antiarrhythmic\n potential, ie, arrhythmia suppression resulting from a\n prolonged APD may, on initiation of a reentrant wave\n front, destabilize the core of a rotating spiral,\n resulting in complex motion (precession) of the spiral\n tip around a nonstationary region of unexcited cells.\n In tissue with inhomogeneities, core instability alters\n the activation sequence from one reentry cycle to the\n next and can lead to spiral wave fractination as the\n wave front collides with inhomogeneous regions.\n Depending on the nature of the inhomogeneities, wave\n front fragments may annihilate one another, producing a\n nonsustained arrhythmia, or may spawn new spirals\n (multiple wavelets), producing fibrillation and sudden\n cardiac death.\",\n bibdate = \"Mon Jan 8 18:24:04 2007\",\n}\n\n","author_short":["Starmer, C.","Romashko, D.","Reddy, R.","Zilberter, Y.","Starobin, J.","Grant, A.","Krinsky, V."],"key":"RSM:Sta95","id":"RSM:Sta95","bibbaseid":"starmer-romashko-reddy-zilberter-starobin-grant-krinsky-proarrhythmicresponsetopotassiumchannelblockadenumericalstudiesofpolymorphictachyarrhythmias-1995","role":"author","urls":{},"metadata":{"authorlinks":{}},"downloads":0,"html":""},"search_terms":["proarrhythmic","response","potassium","channel","blockade","numerical","studies","polymorphic","tachyarrhythmias","starmer","romashko","reddy","zilberter","starobin","grant","krinsky"],"keywords":[],"authorIDs":[],"dataSources":["5HG3Kp8zRwDd7FotB"]}