Objectives: 1/. To study the proarrhythmic effects of intracellular Ca2+ signaling alterations in AF.2/. To study the nuclear Ca2+ signaling in AF.3/. To study the Ca2+-dependent pathways activated in AF and the consequences of the inactivation of…
ID
Source
Brief title
Condition
- Cardiac arrhythmias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters/endpoints:
1/. To identify new cellular proarrhythmic mechanisms.
2/. To identify new nuclear targets for therapy (i.e. important factors
involved in Ca2+-dependent transcription pathways).
Secondary outcome
The knowledge of the cellular mechanisms activated during persistent AF will
significantly enhance the chances of better treatment to not only cardioconvert
AF, but also to allow the atrial cells to recuperate their function after AF.
This is expected to reduce the thromboembolic risks and improve cardiac
function after cardioversion of AF.
Background summary
Rationale: Atrial fibrillation (AF) is the most common sustained cardiac
arrhythmia in adults with growing socio-economic burden. Although a significant
progress has been made in understanding the pathophysiology of this arrhythmia,
treatment of AF patients is still far from satisfactory. AF is characterized by
an electrical remodeling inducing the reduction of the action potential
duration (APD). Intracellular Ca2+ signaling is also altered in AF. Hypotheses:
(1) Reduction of the APD in AF alters the intracellular Ca2+ signal which can
be proarrhythmic; (2) The alterations in intracellular Ca2+ signaling affect
the nuclear Ca2+ signaling which induces the activation specific Ca2+-dependent
transcription pathways in AF.
Study objective
Objectives:
1/. To study the proarrhythmic effects of intracellular Ca2+ signaling
alterations in AF.
2/. To study the nuclear Ca2+ signaling in AF.
3/. To study the Ca2+-dependent pathways activated in AF and the consequences
of the inactivation of these pathways on atrial electrical remodeling and
contraction.
Study design
Study design: Right atrial appendages will be obtained from patients in SR,
with paroxysmal and persistent AF. Sarcomere shortening will be measured in
thin atrial trabeculae and/or isolated cells. Simultaneous recordings of
cellular AP (or ionic currents) and Ca2+ signals will be performed in isolated
atrial cells with the patch-clamp technique coupled to the dynamic confocal
microscopy. Trabeculae or cells will be subjected to different pacing rates,
Ca2+ concentrations, or drugs (i.e. inhibitors of transcription pathways).
Structure and protein composition of the atria will also be studied. Finally,
nuclei will be isolated from atria tissue to specifically study the nuclear
Ca2+ signaling without the influence of the cytoplasmic Ca2+.
Study burden and risks
An informed consent will take place preoperatively. During the operation an
atrial biopt will be prelevated. Biopsy prelevation will prolong the operation
time by about 2 minutes.
Room 3.112 PO Box 616
6200 MD Maastricht
NL
Room 3.112 PO Box 616
6200 MD Maastricht
NL
Listed location countries
Age
Inclusion criteria
Patients in sinus rythm and undergoing for openchest surgery.
Male and female patients over 18 years old.
Patients with paroxysmal AF and undergoing for openchest surgery.
Patients with persistent AF and undergoing for openchest surgery.
Patients who have given written consent.
Exclusion criteria
Patients who are scheduled for re-operation.
Male and female patients under 18 years old.
Patients who do not speak/understand Dutch.
Patients who are not will-competent.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
CCMO | NL31236.068.10 |