Force frequency relationship of the human ventricle increases during early postnatal development.
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 wk) and infants (3-14 mo) 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.
Wiegerinck
Rob F
RF
Department of Pediatrics, Emory University, Atlanta, Georgia 30322, USA.
Cojoc
Anca
A
Zeidenweber
Carlo M
CM
Ding
Guoliang
G
Shen
Ming
M
Joyner
Ronald W
RW
Fernandez
Janet D
JD
Kanter
Kirk R
KR
Kirshbom
Paul M
PM
Kogon
Brian E
BE
Wagner
Mary B
MB
D000367:Age Factors; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D006348:Cardiac Surgical Procedures; D005260:Female; D006330:Heart Defects, Congenital / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery; D006352:Heart Ventricles / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D053580:Muscle Strength; D009200:Myocardial Contraction; D012333:RNA, Messenger / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D016276:Ventricular Function; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D012333:RNA, Messenger; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger; D000099211:Phospholamban