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Force frequency relationship of the human ventricle increases during early postnatal development
Rob F Wiegerinck1, Anca Cojoc, Carlo M Zeidenweber
1Department of Pediatrics, Emory University, Atlanta, Georgia 30322, USA.
Pediatric Research
|January 8, 2009
Summary
Newborns exhibit a flat force frequency response (FFR) in heart muscle, unlike infants whose contractility increases with faster heart rates. This difference is linked to developmental changes in cardiac calcium handling proteins.
Area of Science:
- Cardiovascular Physiology
- Pediatric Cardiology
- Developmental Biology
Background:
- Understanding cardiac contractility development is crucial for treating pediatric heart conditions.
- Neonatal and infant cardiac function differs significantly from adults, impacting therapeutic strategies.
Purpose of the Study:
- To investigate developmental changes in human ventricular contractility and calcium handling from newborn to infant stages.
- To characterize the force frequency response (FFR) and associated protein expression in different pediatric age groups.
Main Methods:
- Isometric developed force measurement in human ventricular muscle strips from newborns (<2 wk) and infants (3-14 mo).
- Assessment of the force frequency response (FFR) across various cycle lengths (CLs).
- Quantification of Na/Ca exchanger (NCX), SERCA, and phospholamban (PLB) mRNA and protein levels, with cellular localization studies.
Main Results:
- Infants demonstrated a positive FFR, with increased developed force at shorter CLs, while newborns showed a flat FFR.
- Newborns had higher NCX mRNA and protein levels compared to infants; SERCA levels were unchanged.
- PLB mRNA levels and the PLB/SERCA ratio increased with age, and NCX localization shifted from peripheral to T-tubules in infant cells.
Conclusions:
- The newborn human ventricle exhibits a flat FFR, which matures to a positive FFR in infants, suggesting age-dependent alterations in cardiac contractility.
- Developmental changes in calcium handling proteins, particularly NCX and PLB, likely underlie the observed differences in FFR and contractility.
- These findings provide critical insights into the maturation of cardiac function in early life and inform therapeutic approaches for congenital heart disease.
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