title: Postnatal Development of Right Ventricular Myofibrillar Biomechanics in Relation to the Sarcomeric Protein Phenotype in Pediatric Patients with Conotruncal Heart Defects.
abstract: The postnatal development of myofibrillar mechanics, a major determinant of heart function, is unknown in pediatric patients with tetralogy of Fallot and related structural heart defects. We therefore determined the mechanical properties of myofibrils isolated from right ventricular tissue samples from such patients in relation to the developmental changes of the isoforms expression pattern of key sarcomere proteins involved in the contractile process.
  
  
  
  Tissue samples from the infundibulum obtained during surgery from 25 patients (age range 15 days to 11 years, median 7 months) were split into half for mechanical investigations and expression analysis of titin, myosin heavy and light chain 1, troponin-T, and troponin-I. Of these proteins, fetal isoforms of only myosin light chain 1 (ALC-1) and troponin-I (ssTnI) were highly expressed in neonates, amounting to, respectively, 40% and 80%, while the other proteins had switched to the adult isoforms before or around birth. ALC-1 and ssTnI expression subsequently declined monoexponentially with a halftime of 4.3 and 5.8 months, respectively. Coincident with the expression of ssTnI, Ca(2+) sensitivity of contraction was high in neonates and subsequently declined in parallel with the decline in ssTnI expression. Passive tension positively correlated with Ca(2+) sensitivity but not with titin expression. Contraction kinetics, maximal Ca(2+)-activated force, and the fast phase of the biphasic relaxation positively correlated with the expression of ALC-1.
  
  
  
  The developmental changes in myofibrillar biomechanics can be ascribed to fetal-to-adult isoform transition of key sarcomeric proteins, which evolves regardless of the specific congenital cardiac malformations in our pediatric patients.
authors.affiliation: Institute of Vegetative Physiology, University of Cologne, Köln, Germany.
authors.forename: Fatiha
authors.initials: F
authors.lastname: Elhamine
authors.affiliation: Institute of Vegetative Physiology, University of Cologne, Köln, Germany Department of Physical Chemistry, University of Bucharest, Romania.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Iorga
authors.affiliation: Institute of Vegetative Physiology, University of Cologne, Köln, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Krüger
authors.affiliation: Clinics for Anesthesiology and Surgical Intensive Care, University of Cologne, Köln, Germany.
authors.forename: Mona
authors.initials: M
authors.lastname: Hunger
authors.affiliation: Institute of Vegetative Physiology, University of Cologne, Köln, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Eckhardt
authors.affiliation: Pediatric Cardiology, University of Cologne, Köln, Germany.
authors.forename: Narayanswami
authors.initials: N
authors.lastname: Sreeram
authors.affiliation: Pediatric Heart Surgery, University of Cologne, Köln, Germany.
authors.forename: Gerardus
authors.initials: G
authors.lastname: Bennink
authors.affiliation: Pediatric Cardiology, University of Cologne, Köln, Germany.
authors.forename: Konrad
authors.initials: K
authors.lastname: Brockmeier
authors.affiliation: Institute of Vegetative Physiology, University of Cologne, Köln, Germany gabriele.pfitzer@uni-koeln.de.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pfitzer
authors.affiliation: Institute of Vegetative Physiology, University of Cologne, Köln, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Stehle
mesh_terms: D001696:Biomechanical Phenomena / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D064211:Connectin / Q000378:metabolism; D006321:Heart / Q000254:growth & development; D006330:Heart Defects, Congenital / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009124:Muscle Proteins / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology; D009210:Myofibrils / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D012518:Sarcomeres / Q000502:physiology; D019210:Troponin I / Q000378:metabolism; D020107:Troponin T / Q000378:metabolism
chemical_list: D064211:Connectin; D009124:Muscle Proteins; D018994:Myosin Light Chains; D019210:Troponin I; D020107:Troponin T; D018995:Myosin Heavy Chains
keywords: cardiac myofibrils; contractile function; contractile proteins; force kinetics; heart development; human myocardium; sarcomere physiology; tetralogy of Fallot