Bioengineered analog of stromal cell-derived factor 1α preserves the biaxial mechanical properties of native myocardium after infarction.
J Mech Behav Biomed Mater
; 96: 165-171, 2019 08.
Article
en En
| MEDLINE
| ID: mdl-31035067
Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) results in abnormal tissue biomechanics and impaired cardiac function, often leading to heart failure. We hypothesized that intramyocardial delivery of engineered stromal cell-derived factor 1α analog (ESA), our previously-developed supra-efficient pro-angiogenic chemokine, preserves biaxial LV mechanical properties after MI. Male Wistar rats (nâ¯=â¯45) underwent sham surgery (nâ¯=â¯15) or permanent left anterior descending coronary artery ligation. Rats sustaining MI were randomized for intramyocardial injections of either saline (100⯵L, nâ¯=â¯15) or ESA (6⯵g/kg, nâ¯=â¯15), delivered at four standardized borderzone sites. After 4 weeks, echocardiography was performed, and the hearts were explanted. Tensile testing of the anterolateral LV wall was performed using a displacement-controlled biaxial load frame, and modulus was determined after constitutive modeling. At 4 weeks post-MI, compared to saline controls, ESA-treated hearts had greater wall thickness (1.68⯱â¯0.05â¯mm vs 1.42⯱â¯0.08â¯mm, pâ¯=â¯0.008), smaller end-diastolic LV internal dimension (6.88⯱â¯0.29â¯mm vs 7.69⯱â¯0.22â¯mm, pâ¯=â¯0.044), and improved ejection fraction (62.8⯱â¯3.0% vs 49.4⯱â¯4.5%, pâ¯=â¯0.014). Histologic analysis revealed significantly reduced infarct size for ESA-treated hearts compared to saline controls (29.4⯱â¯2.9% vs 41.6⯱â¯3.1%, pâ¯=â¯0.021). Infarcted hearts treated with ESA exhibited decreased modulus compared to those treated with saline in both the circumferential (211.5⯱â¯6.9â¯kPa vs 264.3⯱â¯12.5â¯kPa, pâ¯=â¯0.001) and longitudinal axes (194.5⯱â¯6.5â¯kPa vs 258.1⯱â¯14.4â¯kPa, pâ¯<â¯0.001). In both principal directions, ESA-treated infarcted hearts possessed similar tissue compliance as sham non-infarcted hearts. Overall, intramyocardial ESA therapy improves post-MI ventricular remodeling and function, reduces infarct size, and preserves native LV biaxial mechanical properties.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ingeniería de Proteínas
/
Quimiocina CXCL12
/
Fenómenos Mecánicos
/
Corazón
/
Infarto del Miocardio
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Mech Behav Biomed Mater
Asunto de la revista:
ENGENHARIA BIOMEDICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos