Natural cardiac regeneration conserves native biaxial left ventricular biomechanics after myocardial infarction in neonatal rats

Hanjay Wang; Andrew Wisneski; Annabel M Imbrie-Moore; Michael J Paulsen; Zhongjie Wang; Yue Xuan; Hector Lopez Hernandez; Camille E Hironaka; Haley J Lucian; Hye Sook Shin; Shreya Anilkumar; Akshara D Thakore; Justin M Farry; Anahita Eskandari; Kiah M Williams; Frederick Grady; Matthew A Wu; Jinsuh Jung; Lyndsay M Stapleton; Amanda N Steele; Yuanjia Zhu; Y Joseph Woo

doi:10.1016/j.jmbbm.2022.105074

Natural cardiac regeneration conserves native biaxial left ventricular biomechanics after myocardial infarction in neonatal rats

J Mech Behav Biomed Mater. 2022 Feb:126:105074. doi: 10.1016/j.jmbbm.2022.105074. Epub 2022 Jan 4.

Authors

Hanjay Wang¹, Andrew Wisneski², Annabel M Imbrie-Moore³, Michael J Paulsen⁴, Zhongjie Wang², Yue Xuan², Hector Lopez Hernandez⁵, Camille E Hironaka⁴, Haley J Lucian⁴, Hye Sook Shin⁴, Shreya Anilkumar⁴, Akshara D Thakore⁴, Justin M Farry⁴, Anahita Eskandari⁴, Kiah M Williams⁴, Frederick Grady⁴, Matthew A Wu⁴, Jinsuh Jung⁴, Lyndsay M Stapleton⁶, Amanda N Steele⁶, Yuanjia Zhu⁶, Y Joseph Woo⁷

Affiliations

¹ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
² Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
³ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Department of Mechanical Engineering, Stanford University, Stanford, CA, USA.
⁴ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
⁵ Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
⁶ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA.
⁷ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA. Electronic address: joswoo@stanford.edu.

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 (267.9 kPa vs 274.2 kPa, p = 0.7847), longitudinal modulus (269.3 kPa vs 277.1 kPa, p = 0.7435), and maximum shear stress (3.30 kPa vs 3.95 kPa, 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 (321.5 kPa vs 180.0 kPa, p = 0.0111) and longitudinal axes (315.4 kPa vs 172.3 kPa, p = 0.0173), and also exhibited greater maximum shear stress (14.87 kPa vs 3.23 kPa, 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.

Keywords: Biaxial tension; Heart; Myocardial infarction; Neonate; Regeneration; Ventricular remodeling.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Animals, Newborn
Biomechanical Phenomena
Cicatrix / pathology
Disease Models, Animal
Myocardial Infarction* / pathology
Myocardium / pathology
Rats
Rats, Wistar
Ventricular Remodeling

Abstract

Publication types

MeSH terms

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