Abstract 18368: Characterization of Myofibril Mechanics in Pediatric and Adult Patients With Idiopathic Dilated Cardiomyopathy

Introduction: We studied mechanical properties of myofibrils from children and adults with and without HF to determine: 1) baseline myofibril characteristics, 2) differences between children and adults, 3) myofibril mechanics in the setting of HF. Hypothesis: Myofibril mechanics are different between adults and children. Methods: Myofibrils were obtained from pediatric and adult patients with idiopathic dilated cardiomyopathy (IDC) undergoing cardiac transplantation. Unused donor hearts were used as non-failing control (NF). Written informed consent was obtained and experiments were approved by the University of Colorado Institutional Review Board. Myofibril mechanical properties measured were: resting sarcomere length (SL, μm), resting and maximal tension (RT, T max , mN/mm 2 ); rate constant of tension development ( k ACT , S -1 ); duration of linear relaxation ( t LIN , mSec), rate constant of linear and exponential relaxation (linear and exponential 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 2.10±0.01, P 2 vs 10.3±0.7 P t LIN (192.4±7.5 msec vs 153.4±3.7, P k REL (7.8±0.4 S -1 vs 15.4±0.8, P max , k ACT , and linear k REL were similar. In the adult group, IDC myofibrils showed slower k ACT (0.45±0.02 S -1 vs 0.57±0.03, P k REL (11.9±0.7 S -1 vs 15.4+0.8, P max , t LIN, and linear k REL were similar. In the pediatric group, IDC myofibrils developed lower T max (35.3±2.5 mN/mm 2 vs 57.5+4.4, P t LIN (136.6±3.2 msec vs 202.3±8.9, P k REL (0.36±0.03 vs 0.57±0.06 P k ACT and exponential k REL were similar. Conclusions: NF myofibrils from children have shorter resting SL and slower relaxation kinetics than NF adults. While myofibrils from adult IDC display slower activation and exponential relaxation kinetics, children with IDC display altered linear relaxation kinetics and reduced tension generation. These results show that myofibrils from children have fundamental differences in mechanical characteristics at baseline and in response to heart failure.