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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
Sponsor:
Information provided by (Responsible Party):

October 24, 2005
October 25, 2005
August 17, 2017
April 2005
August 31, 2019   (Final data collection date for primary outcome measure)
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.
Not Provided
Complete list of historical versions of study NCT00243776 on ClinicalTrials.gov Archive Site
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Calcium Current in Human Heart Cells
Calcium Current in Human Atrial Myocytes
The study team will use small pieces of human hearts which are removed as part of a required surgical procedure to study how calcium ions pass through the membrane of heart cells in order to tell the heart cell how much force to contract with when the heart beats. Investigators will also study the proteins and RNA of these pieces to determine how the newborn heart cells control their force of contraction differently from adult heart cells. Investigators hypothesize that infant hearts have different regulation of calcium entry than adult hearts.

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:

  1. 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.
  2. 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.
  3. 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.
  4. 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.
Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples Without DNA
Description:
tissue obtained from surgical waste tissue
Probability Sample
Children undergoing surgery for repair of congenital heart disease
  • Congenital Heart Disease
  • Tetralogy of Fallot
Not Provided
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Wiegerinck RF, Cojoc A, Zeidenweber CM, Ding G, Shen M, Joyner RW, Fernandez JD, Kanter KR, Kirshbom PM, Kogon BE, Wagner MB. Force frequency relationship of the human ventricle increases during early postnatal development. Pediatr Res. 2009 Apr;65(4):414-9. doi: 10.1203/PDR.0b013e318199093c.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
600
August 31, 2019
August 31, 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients undergoing cardiopulmonary bypass surgery

Exclusion Criteria:

  • Prior cardiac surgery
  • History of atrial fibrillation or other atrial arrhythmias prior to operation
Sexes Eligible for Study: All
up to 18 Years   (Child, Adult)
No
Contact: Michael E Davis, PhD 404-727-9858 medavis@emory.edu
Contact: Janet Fernandez, RN 4047851731 janet.fernandez@choa.org
United States
 
 
NCT00243776
IRB00005500
NIH R01HL077485
No
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Michael Davis, Emory University
Emory University
Not Provided
Principal Investigator: Michael E Davis, PhD Emory University
Emory University
August 2017