Myofibrillar protein expression and contractility in congenital heart diseases associated with right ventricular hypertrophy

  • Dr Lotfi Ben Mime, Department of Cardiothoracic Surgery, University of Cologne, Cologne, Germany, Germany
  • F Elhamine, Institute of Vegetative Physiology, University of Cologne, Cologne, Germany, Germany
  • B Iorga, Institute of Vegetative Physiology, University of Cologne, Cologne, Germany
  • R Stehle, Institute of Vegetative Physiology, University of Cologne, Cologne, Germany, Germany
  • G Pfitzer, Institute of Vegetative Physiology, University of Cologne, Cologne, Germany, Germany
  • N Sreeram, Pediatric Cardiology, University of Cologne, Cologne, Germany, Germany
  • K Brockmeier, Pediatric Cardiology, University of Cologne, Cologne, Germany, Germany
  • G Bennink, Department of Cardiothoracic Surgery, University of Cologne, Cologne, Germany, Germany

    • Objectives: Congenital heart diseases with right ventricular outflow tract obstruction such as Tetralogy of Fallot are characterized by a hypertrophied RV. We examined kinetics of myofibrillar force development and relaxation, Ca2+-sensitivity of force generation and sarcomeric protein isoform expression from resections taken from the RV during surgical correction at different stage of postnatal development [n=9].
    Methods: Contractile parameters were determined using techniques based on the principle of atomic force microscopy and rapid solution change. Subcellular myofibrils were isolated from RV resections.Thin bundles of cardiac myofibrils were installed in the apparatus described by Stehle et al. and force kinetics were induced by rapid solution change (within ~10 ms) technique described by Colomo et al.
    Results: There is a down regulation of ssTnI and ALC-1 expression as well as a decrease of Ca2+-sensitivity of myofibrils with increasing age (neonates [n=5], pCa50 = 5,95 ± 0,03 versus 3 year-old infants [n=4], pCa50 = 5,33 ± 0,05). However, there is a difference in the rate of Ca2+-sensivity decrease among the study population. There is a significant positive correlation between pCa50, ALC-1 and ssTnI expression level. ALC-1 expression correlates positively with the contraction kinetics and the rapid phase of relaxation (kRE) as well as with Ca2+- and mechanically-induced force kinetics (kACT, kTR). Contraction and relaxation kinetics are not affected by ssTnI, which shows a delayed down-regulation over age.
    Conclusions: ALC-1 down-regulation over age affects myocardial kinetics negatively. However, because ssTnI is relatively pH-insensitive its delayed down-regulation may be beneficial for myocardial function.