Model-based analysis of the effects of thioridazine enantiomers on the rabbit papillary action potential

Publikation: Bidrag til bog/antologi/rapport › Konferencebidrag i proceedings › Forskning › fagfællebedømt

Standard

Model-based analysis of the effects of thioridazine enantiomers on the rabbit papillary action potential. / Jensen, Ask S.; Pennisi, Cristian P.; Sevcencu, Cristian; Christensen, Jørn B.; Kristiansen, Jette E.; Struijk, Johannes J.

Computing in Cardiology Conference 2015, CinC 2015. red. / Alan Murray. IEEE Computer Society Press, 2015. s. 1089-1092 7411104 (Computing in Cardiology, Bind 42).

Publikation: Bidrag til bog/antologi/rapport › Konferencebidrag i proceedings › Forskning › fagfællebedømt

Harvard

Jensen, AS, Pennisi, CP, Sevcencu, C, Christensen, JB, Kristiansen, JE & Struijk, JJ 2015, Model-based analysis of the effects of thioridazine enantiomers on the rabbit papillary action potential. i A Murray (red.), Computing in Cardiology Conference 2015, CinC 2015., 7411104, IEEE Computer Society Press, Computing in Cardiology, bind 42, s. 1089-1092, 42nd Computing in Cardiology Conference, CinC 2015, Nice, Frankrig, 06/09/2015. https://doi.org/10.1109/CIC.2015.7411104

APA

Jensen, A. S., Pennisi, C. P., Sevcencu, C., Christensen, J. B., Kristiansen, J. E., & Struijk, J. J. (2015). Model-based analysis of the effects of thioridazine enantiomers on the rabbit papillary action potential. I A. Murray (red.), Computing in Cardiology Conference 2015, CinC 2015 (s. 1089-1092). [7411104] IEEE Computer Society Press. Computing in Cardiology Bind 42 https://doi.org/10.1109/CIC.2015.7411104

Vancouver

Jensen AS, Pennisi CP, Sevcencu C, Christensen JB, Kristiansen JE, Struijk JJ. Model-based analysis of the effects of thioridazine enantiomers on the rabbit papillary action potential. I Murray A, red., Computing in Cardiology Conference 2015, CinC 2015. IEEE Computer Society Press. 2015. s. 1089-1092. 7411104. (Computing in Cardiology, Bind 42). https://doi.org/10.1109/CIC.2015.7411104

Author

Jensen, Ask S. ; Pennisi, Cristian P. ; Sevcencu, Cristian ; Christensen, Jørn B. ; Kristiansen, Jette E. ; Struijk, Johannes J. / Model-based analysis of the effects of thioridazine enantiomers on the rabbit papillary action potential. Computing in Cardiology Conference 2015, CinC 2015. red. / Alan Murray. IEEE Computer Society Press, 2015. s. 1089-1092 (Computing in Cardiology, Bind 42).

Bibtex

@inproceedings{4efdb0b86f6f495e91a86afd5e7b0c7f,
title = "Model-based analysis of the effects of thioridazine enantiomers on the rabbit papillary action potential",
abstract = "Aims: We investigated mechanisms underlying the effects of the thioridazine enantiomers on the rabbit papillary action potential duration (AP, APD). Methods: An adapted computational model of the rabbit ventricular action potential was used to carry out a model-based analysis of transmembrane AP recordings from isolated right ventricular papillary muscles from 21 rabbits in four groups: control, (-)-thioridazine, (+)thioridazine, and racemate. Drug effects were determined using an inverse method and a forward method. Effects were modeled by inhibition of the IKr and ICaL currents. Results: Simultaneous inhibition of IKr and ICaL resulted in a more accurate description of the observed drug effects than could IKr inhibition alone. The following values of IKr inhibition at 10 mg L-1 were determined. Forward method: Racemate = 45%, (-)-thioridazine = 0%, and (+)-thioridazine = 85%. Inverse method: (-)thioridazine = 35%, (+)-thioridazine = 80%. Conclusion: Ikr inhibition accurately described the observed APD prolongation, and the identified levels of IKr inhibition were plausible when compared to literature. Both methods found (-)-thioridazine to cause less IKr inhibition than (+ )-thioridazine or the racemate. These results indicate that the prolonging effects observed in the experiment may be related to IKr inhibition.",
author = "Jensen, {Ask S.} and Pennisi, {Cristian P.} and Cristian Sevcencu and Christensen, {J{\o}rn B.} and Kristiansen, {Jette E.} and Struijk, {Johannes J.}",
year = "2015",
month = feb,
day = "16",
doi = "10.1109/CIC.2015.7411104",
language = "English",
series = "Computing in Cardiology",
publisher = "IEEE Computer Society Press",
pages = "1089--1092",
editor = "Alan Murray",
booktitle = "Computing in Cardiology Conference 2015, CinC 2015",
address = "United States",
note = "42nd Computing in Cardiology Conference, CinC 2015 ; Conference date: 06-09-2015 Through 09-09-2015",

}

RIS

TY - GEN

T1 - Model-based analysis of the effects of thioridazine enantiomers on the rabbit papillary action potential

AU - Jensen, Ask S.

AU - Pennisi, Cristian P.

AU - Sevcencu, Cristian

AU - Christensen, Jørn B.

AU - Kristiansen, Jette E.

AU - Struijk, Johannes J.

PY - 2015/2/16

Y1 - 2015/2/16

N2 - Aims: We investigated mechanisms underlying the effects of the thioridazine enantiomers on the rabbit papillary action potential duration (AP, APD). Methods: An adapted computational model of the rabbit ventricular action potential was used to carry out a model-based analysis of transmembrane AP recordings from isolated right ventricular papillary muscles from 21 rabbits in four groups: control, (-)-thioridazine, (+)thioridazine, and racemate. Drug effects were determined using an inverse method and a forward method. Effects were modeled by inhibition of the IKr and ICaL currents. Results: Simultaneous inhibition of IKr and ICaL resulted in a more accurate description of the observed drug effects than could IKr inhibition alone. The following values of IKr inhibition at 10 mg L-1 were determined. Forward method: Racemate = 45%, (-)-thioridazine = 0%, and (+)-thioridazine = 85%. Inverse method: (-)thioridazine = 35%, (+)-thioridazine = 80%. Conclusion: Ikr inhibition accurately described the observed APD prolongation, and the identified levels of IKr inhibition were plausible when compared to literature. Both methods found (-)-thioridazine to cause less IKr inhibition than (+ )-thioridazine or the racemate. These results indicate that the prolonging effects observed in the experiment may be related to IKr inhibition.

AB - Aims: We investigated mechanisms underlying the effects of the thioridazine enantiomers on the rabbit papillary action potential duration (AP, APD). Methods: An adapted computational model of the rabbit ventricular action potential was used to carry out a model-based analysis of transmembrane AP recordings from isolated right ventricular papillary muscles from 21 rabbits in four groups: control, (-)-thioridazine, (+)thioridazine, and racemate. Drug effects were determined using an inverse method and a forward method. Effects were modeled by inhibition of the IKr and ICaL currents. Results: Simultaneous inhibition of IKr and ICaL resulted in a more accurate description of the observed drug effects than could IKr inhibition alone. The following values of IKr inhibition at 10 mg L-1 were determined. Forward method: Racemate = 45%, (-)-thioridazine = 0%, and (+)-thioridazine = 85%. Inverse method: (-)thioridazine = 35%, (+)-thioridazine = 80%. Conclusion: Ikr inhibition accurately described the observed APD prolongation, and the identified levels of IKr inhibition were plausible when compared to literature. Both methods found (-)-thioridazine to cause less IKr inhibition than (+ )-thioridazine or the racemate. These results indicate that the prolonging effects observed in the experiment may be related to IKr inhibition.

U2 - 10.1109/CIC.2015.7411104

DO - 10.1109/CIC.2015.7411104

M3 - Article in proceedings

AN - SCOPUS:84964012150

T3 - Computing in Cardiology

SP - 1089

EP - 1092

BT - Computing in Cardiology Conference 2015, CinC 2015

A2 - Murray, Alan

PB - IEEE Computer Society Press

T2 - 42nd Computing in Cardiology Conference, CinC 2015

Y2 - 6 September 2015 through 9 September 2015

ER -

ID: 261046493