Calcium Current in Human Heart Cells
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|ClinicalTrials.gov Identifier: NCT00243776|
Recruitment Status : Recruiting
First Posted : October 25, 2005
Last Update Posted : August 17, 2017
|Condition or disease|
|Congenital Heart Disease Tetralogy of Fallot|
Extrapolating pharmacological and surgical therapies from adult (AD) studies to infant (INF) patients is problematic because the knowledge of cellular electrophysiology and molecular biology of human INF heart cells is limited. The investigators have studied developmental differences in rabbit ventricular cells and now extend these studies to atrial and ventricular cells isolated from AD, young adult (YAD) or INF patients.
The study aims are as follows:
- Developmental differences in transient outward current of atrial cells. Investigators will extend their studies to isolated cells and tissue from YADs (age 14-20). In addition, several other accessory beta-subunits have been found in cardiac myocytes and may interact with Kv channels and regulate the function of these channels. The study team will determine relative amounts of these putative regulators of human atrial Ito to determine which correlate with developmental changes in Ito kinetics.
- Developmental differences in amplitude and regulation of calcium current in atrial cells. Investigators hypothesize that INF atrial cells have tonic inhibition of adenylyl cyclase (and thus of ICa) mediated by inhibitory G proteins, possibly related to constitutive activity of the adenosine A1 receptor, and that, compared to AD or YAD cells, have greater sensitivity to inhibitors of phosphatases and phosphodiesterases, and that developmental changes in basal ICa amplitude and beta-sympathetic modulation correlate with inhibitory G protein levels, receptor numbers for M2 and A1 receptors, and constitutive inhibitory activity.
- Modulation of atrial cell calcium transients by changes in AP waveform and developmental age. The study team will test the hypothesis that prolongation of the early repolarization phase of the AP increases Ca2+ entry and that YAD cells have faster removal of Ca2+ from cytoplasm than INF cells and will determine if the Na- Ca2+ exchange current (INCX) is greater in INF vs. AD or YAD cells.
- Developmental differences in Ca current and transients and contractility in ventricular cells. Investigators propose that INF cells and tissue have lower basal ICa, lower potency for ISO stimulation, higher levels of Gialpha3 and A1 receptors, greater inhibitory potency for adenosine, and tonic inhibition of ICa. We also propose that the YAD cells have lower levels of NCX and lower INCX, higher levels of SERCA and faster removal of Ca2+ from the cytoplasm. Previous animal studies have indicated various developmental changes in cardiac cells. We will specifically study human postnatal developmental changes in Ito, regulation of ICa and intracellular Ca2+ transients.
|Study Type :||Observational|
|Estimated Enrollment :||600 participants|
|Official Title:||Calcium Current in Human Atrial Myocytes|
|Study Start Date :||April 2005|
|Estimated Primary Completion Date :||August 31, 2019|
|Estimated Study Completion Date :||August 31, 2019|
- Calcium Current Measures [ Time Frame: Duration of Study (Up to 13 Years) ]Calcium currents including transients and modulation of calcium handling by activation of different pathways in isolated cells from waste tissue obtained at the time of surgical repair for CHD will be measured for the duration of the study.
Biospecimen Retention: Samples Without DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00243776
|Contact: Michael E Davis, PhDfirstname.lastname@example.org|
|Contact: Janet Fernandez, RNemail@example.com|
|United States, Georgia|
|Emory University School of Medicine||Recruiting|
|Atlanta, Georgia, United States, 30322|
|Principal Investigator: Mary B Wagner, PhD|
|Principal Investigator:||Michael E Davis, PhD||Emory University|