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Author Notes:

Corresponding author: Mary B. Wagner, PhD Department of Pediatrics, Emory University 2015 Uppergate Drive, 336 Atlanta, GA 30322 Phone: 1-404-727-1336 FAX: 1-404-727-6024 mary.wagner@emory.edu

R.F.W. and A.C. contributed equally to this study.


Research Funding:

National Heart, Lung, and Blood Institute : NHLBI

Financial Support: This work was supported by National Heart, Lung and Blood Institute Grants HL-088488 (MBW) and HL-077485 (RWJ), and American Heart Association Southeast Affiliate Grant in Aid 0755537B (MBW) and by financial support from Children's Healthcare of Atlanta.


  • Pediatric and congenital heart disease
  • Developmental biology
  • Contractile function
  • Heart failure - basic studies

Force Frequency Relationship of the Human Ventricle Increases During Early Postnatal Development

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Journal Title:

Pediatric Research


Volume 65, Number 4


, Pages 414-419

Type of Work:

Article | Post-print: After Peer Review


Understanding developmental changes in contractility is critical to improving therapies for young cardiac patients. Isometric developed force was measured in human ventricular muscle strips from two age groups: newborns (<2 weeks) and infants (3–14 months) undergoing repair for congenital heart defects. Muscle strips were paced at several cycle lengths (CLs) to determine the force frequency response (FFR). Changes in Na/Ca exchanger (NCX), sarcoplasmic reticulum Ca-ATPase (SERCA) and phospholamban (PLB) were characterized. At CL 2000 ms, developed force was similar in the two groups. Decreasing CL increased developed force in the infant group to 131±8% (CL 1000 ms) and 157±18% (CL 500 ms) demonstrating a positive FFR. The FFR in the newborn group was flat. NCX mRNA and protein levels were significantly larger in the newborn than infant group whereas SERCA levels were unchanged. PLB mRNA levels and PLB/SERCA ratio increased with age. Immunostaining for NCX in isolated newborn cells showed peripheral staining. In infant cells, NCX was also found in T-tubules. SERCA staining was regular and striated in both groups. This study shows for the first time that the newborn human ventricle has a flat FFR, which increases with age and may be caused by developmental changes in calcium handling.

Copyright information:

© 2009 International Pediatric Research Foundation, Inc

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