Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Antoons, G; Willems, R; Sipido, KR.
Alternative strategies in arrhythmia therapy: evaluation of Na/Ca exchange as an anti-arrhythmic target.
Pharmacol Ther. 2012; 134(1):26-42
Doi: 10.1016/j.pharmthera.2011.12.001
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Antoons Gudrun
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- Abstract:
- The search for alternative anti-arrhythmic strategies is fueled by an unmet medical need as well as by the opportunities arising from identification of novel targets and novel drugs. Na/Ca exchange is a potential target involved in several types of arrhythmias, such as those related to ischemia-reperfusion, heart failure and also some forms of genetic arrhythmias. Inhibition of Na/Ca exchange is theoretically not only anti-arrhythmic but also increases cellular Ca(2+) content. This could be an advantage in conditions of low inotropy, such as in heart failure, but may also worsen conditions such as the recovery from ischemia or relaxation abnormalities. With the available drugs such as KB-R7943 and SEA-0400 these theories have now been tested in a number of cellular and in vivo models. Experience is overall rather positive and seems less hampered by the potential drawbacks than expected. This may be because the currently available drugs are not highly selective, with additional benefit derived from concurrent effects. While this precludes a definite answer regarding the benefit of a pure NCX inhibitor, they indicate that Na/Ca exchange inhibition as part of a multi-target strategy is an avenue to be considered. Such studies will need further 'bench' work and testing in relevant preclinical models, including chronic disease.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Anti-Arrhythmia Agents - pharmacology Anti-Arrhythmia Agents - therapeutic use
- Arrhythmias, Cardiac - drug therapy Arrhythmias, Cardiac - metabolism
- Humans -
- Sodium-Calcium Exchanger - metabolism
- Find related publications in this database (Keywords)
- Ventricular arrhythmias
- Heart failure
- Atrial fibrillation
- Na/Ca exchange
- Ryanodine receptor
- Pharmacology