Abstract 724: Neonatal Heart Regeneration Preserves Native Ventricular Biomechanical Properties After Myocardial Infarction

Abstract

Introduction: Neonatal mice exhibit natural heart regeneration after myocardial infarction (MI) until postnatal day 7 (P7). Whether this regenerated muscle is similar biomechanically to native myocardium remains unknown. We hypothesized that neonatal heart regeneration preserves native left ventricular (LV) biomechanical properties after MI. Methods: C57BL/6J mice (n=58) underwent sham surgery or left anterior descending coronary artery ligation on postnatal day 1 (P1) or P7. After 4 weeks, echocardiography was performed. The explanted anterolateral LV wall was mounted for lenticular hydrostatic deformation testing (Fig 1A-B) and pressurized to 130 mmHg with 37°C saline to impart a homogeneous stress load. Surface strain was tracked to calculate a multiaxial composite tissue modulus. Data are expressed as mean±SEM. Results: P1 MI and sham mice (n=14, each) had similar post-MI LV wall thickness (0.61±0.05 cm vs 0.66±0.03 cm, p=0.39), end-diastolic diameter (3.14±0.10 cm vs 3.05±0.12 cm, p=0.57), and ejection fraction (58.2±4.1% vs 55.2±4.4%, p=0.63). P7 MI mice (n=14) had significant LV wall thinning (0.40±0.04 cm vs 0.71±0.02 cm, p<0.0001), end-diastolic LV enlargement (4.24±0.16 cm vs 3.34±0.09 cm, p<0.0001), and depressed ejection fraction (29.7±4.9% vs 61.7±4.0%, p<0.0001) compared to P7 shams (n=16). While LV tissue modulus for P1 MI and sham mice were similar (460.9±46.4 kPa vs 527.1±61.2 kPa, p=0.40, Fig 1C), the modulus for P7 MI mice was significantly elevated compared to that for P7 shams (1099.6±175.1 kPa vs 616.0±95.2 kPa, p=0.02, Fig 1D). Conclusion: In a neonatal mouse MI model, regenerated LV muscle has similar biomechanical properties as native LV muscle.