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Natural cardiac regeneration conserves native biaxial left ventricular biomechanics after myocardial infarction in neonatal rats. Journal of the mechanical behavior of biomedical materials Wang, H., Wisneski, A., Imbrie-Moore, A. M., Paulsen, M. J., Wang, Z., Xuan, Y., Lopez Hernandez, H., Hironaka, C. E., Lucian, H. J., Shin, H. S., Anilkumar, S., Thakore, A. D., Farry, J. M., Eskandari, A., Williams, K. M., Grady, F., Wu, M. A., Jung, J., Stapleton, L. M., Steele, A. N., Zhu, Y., Woo, Y. J. 1800; 126: 105074

Abstract

After myocardial infarction (MI), adult mammals exhibit scar formation, adverse left ventricular (LV) remodeling, LV stiffening, and impaired contractility, ultimately resulting in heart failure. Neonatal mammals, however, are capable of natural heart regeneration after MI. We hypothesized that neonatal cardiac regeneration conserves native biaxial LV mechanics after MI. Wistar rat neonates (1 day old, n=46) and adults (8-10 weeks old, n=20) underwent sham surgery or permanent left anterior descending coronary artery ligation. At 6 weeks after neonatal MI, Masson's trichrome staining revealed negligible fibrosis. Echocardiography for the neonatal MI (n=15) and sham rats (n=14) revealed no differences in LV wall thickness or chamber diameter, and both groups had normal ejection fraction (72.7% vs 77.5%, respectively, p=0.1946). Biaxial tensile testing revealed similar stress-strain curves along both the circumferential and longitudinal axes across a full range of physiologic stresses and strains. The circumferential modulus (267.9kPa vs 274.2kPa, p=0.7847), longitudinal modulus (269.3kPa vs 277.1kPa, p=0.7435), and maximum shear stress (3.30kPa vs 3.95kPa, p=0.5418) did not differ significantly between the neonatal MI and sham groups, respectively. In contrast, transmural scars were observed at 4 weeks after adult MI. Adult MI hearts (n=7) exhibited profound LV wall thinning (p<0.0001), chamber dilation (p=0.0246), and LV dysfunction (ejection fraction 45.4% vs 79.7%, p<0.0001) compared to adult sham hearts (n=7). Adult MI hearts were significantly stiffer than adult sham hearts in both the circumferential (321.5kPa vs 180.0kPa, p=0.0111) and longitudinal axes (315.4kPa vs 172.3kPa, p=0.0173), and also exhibited greater maximum shear stress (14.87kPa vs 3.23kPa, p=0.0162). Our study is the first to show that native biaxial LV mechanics are conserved after neonatal heart regeneration following MI, thus adding biomechanical support for the therapeutic potential of cardiac regeneration in the treatment of ischemic heart disease.

View details for DOI 10.1016/j.jmbbm.2022.105074

View details for PubMedID 35030471