Dynamic system analysis of receptor interaction and effectuation mechanisms of digoxin in the rat heart [Elektronische Ressource] / von Myoungki Baek

Allosophy

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• Gesundheit

Informations

• Publié par: martin-luther-universitat_halle-wittenberg
• Publié le: 01 janvier 2005
• Nombre de lectures: 29
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Dynamic System Analysis of Receptor Interaction and
Effectuation Mechanisms of Digoxin in the Rat Heart







Dissertation

Zur Erlangung des akademischen Grades
doctor rerum naturalium (Dr. rer. nat)



vorgelegt der


Mathematisch-Naturwissenschaftlich-Technischen Fakultät
der Martin-Luther-Universität Halle-Wittenberg




von Myoungki Baek, MS.
geb. 02. 09. 1970 in Daejon, Südkorea




Gutachter:
1. Prof. Dr. Michael Weiss
2. Prof. Dr. Reinhard Neubert
3. Prof. Dr. Richard Süverkrüp

Halle (Saale), den 06. 04. 2005


urn:nbn:de:gbv:3-000008190
[http://nbn-resolving.de/urn/resolver.pl?urn=nbn%3Ade%3Agbv%3A3-000008190]


Table of Contents

1. Introduction
1.1 Cardiac glycosides ························································································· 1
1.2 Physiology of cardiac muscle ········································································· 4
1.3 Inotropic response of cardiac glycosides ······················································· 6
+ + 1.3.1 Inhibition of Na ,K -ATPase ································································ 6
+ 2+ 1.3.2 Role of Na /Ca Exchanger ································································· 7
1.4 Disease states ································································································· 10
1.5 PK/PD modeling ···························································································· 11
1.6 Purpose ··········································································································· 14

2. Materials and Method
2.1 Materials ········································································································· 16
2.2 Isolated perfused heart ··················································································· 17
2.3 Experimental protocol ···················································································· 19
2.4 Hypertrophy inducement ················································································ 19
2.5 Sepsis inducement ·························································································· 20
2.6 Determination of digoxin in perfusate ··························································· 20

3. Model development and data analysis
3.1 Mechanistic model of digoxin ········································································ 21
3.1.1 Myocardial uptake and binding processes ············································ 21
3.1.2 Kinetics of receptor binding and cellular effectuation ·························· 23
3.2 Data analysis ··················································································&#