Abstract 57: Myofibrils From Pediatric IDC Patients Display Faster Relaxation Kinetics and Reduced Tension Generation

Abstract

Objective: Pediatric patients with heart failure, compared to adults, respond differently to current armamentarium of heart failure (HF) therapeutics, indicating differences in the hearts of children and adults. We examined myofibril mechanics in children and adults with and without HF to determine: 1) baseline myofibril characteristics, 2) differences between children and adults, and 3) myofibril mechanics in the setting of HF. Methods: Myofibrils were obtained from pediatric and adult patients with IDC undergoing cardiac transplantation. Unused donor hearts were used as non-failing control (NF). Written informed consent was obtained. Myofibrils were stretched from slack length and set 5-10% above slack sarcomere length (SL), and Ca 2+ -activated and relaxed at 15°C. Mechanical and kinetic parameters: maximal tension (T max , mN/mm 2 ); rate constant of tension development ( k ACT , S -1 ); duration of slow relaxation phase ( t LIN , mSec), rate constant of fast phase relaxation ( k REL , S -1 ). Mechanical parameters ± SEM are shown. Results: Compared to NF adults, myofibrils from NF pediatric hearts had shorter SL (2.04±0.01 μm vs 2.11±0.01, p < 0.0001), slower t LIN (202.7+9.0 msec vs 152.9+4.1, p < 0.0001) and slower k REL (7.8+0.4 S -1 vs 15.7+0.8, p < 0.0001). T max and k ACT were similar. In the adult cohort, myofibrils from adult IDC patients showed slower k ACT (0.45+0.02 S -1 vs 0.57+0.03, p < 0.005) and slower k REL (11.9+0.7 S -1 vs 15.7+0.8, p < 0.005). T max and t LIN were similar. In the pediatric cohort, myofibrils from IDC developed lower T max (35.3+2.5 mN/mm 2 vs 57.5+4.4, p < 0.0001), and faster t LIN (136.6+3.2 msec vs 202.3+8.9, p < 0.0001) and faster k REL (9.1+0.4 S -1 vs 7.8+0.4, p < 0.05). k ACT was similar. Conclusion: NF myofibrils from children have shorter resting SL and slower relaxation kinetics than NF adults. While myofibrils from adults IDC result in slower activation and exponential relaxation kinetics, children with IDC display faster relaxation kinetic and reduced tension generation. These results show that myofibrils from children have fundamental differences in mechanical characteristics at baseline and in the setting of heart failure.