title: Mathematically engineered stromal cell-derived factor-1α stem cell cytokine analog enhances mechanical properties of infarcted myocardium.
abstract: OBJECTIVE
  The biomechanical response to a myocardial infarction consists of ventricular remodeling that leads to dilatation, loss of contractile function, abnormal stress patterns, and ultimately heart failure. We hypothesized that intramyocardial injection of our previously designed pro-angiogenic chemokine, an engineered stromal cell-derived factor-1α analog (ESA), improves mechanical properties of the heart after infarction.
  
  
  METHODS
  Male rats (n = 54) underwent either sham surgery (n = 17) with no coronary artery ligation or ligation of the left anterior descending artery (n = 37). The rats in the myocardial infarction group were then randomized to receive either saline (0.1 mL, n = 18) or ESA (6 μg/kg, n = 19) injected into the myocardium at 4 predetermined spots around the border zone. Echocardiograms were performed preoperatively and before the terminal surgery. After 4 weeks, the hearts were explanted and longitudinally sectioned. Uniaxial tensile testing was completed using an Instron 5543 Microtester. Optical strain was evaluated using custom image acquisition software, Digi-Velpo, and analyzed in MATLAB.
  
  
  RESULTS
  Compared with the saline control group at 4 weeks, the ESA-injected hearts had a greater ejection fraction (71.8% ± 9.0% vs 55.3% ± 12.6%, P = .0004), smaller end-diastolic left ventricular internal dimension (0.686 ± 0.110 cm vs 0.763 ± 0.160 cm, P = .04), greater cardiac output (36 ± 11.6 mL/min vs 26.9 ± 7.3 mL/min, P = .05), and a lower tensile modulus (251 ± 56 kPa vs 301 ± 81 kPa, P = .04). The tensile modulus for the sham group was 195 ± 56 kPa, indicating ESA injection results in a less stiff ventricle.
  
  
  CONCLUSIONS
  Direct injection of ESA alters the biomechanical response to myocardial infarction, improving the mechanical properties in the postinfarct heart.
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: MacArthur
authors.forename: Alen
authors.initials: A
authors.lastname: Trubelja
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shudo
authors.forename: Philip
authors.initials: P
authors.lastname: Hsiao
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Fairman
authors.forename: Elaine
authors.initials: E
authors.lastname: Yang
authors.forename: William
authors.initials: W
authors.lastname: Hiesinger
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Sarver
authors.forename: Pavan
authors.initials: P
authors.lastname: Atluri
authors.forename: Y Joseph
authors.initials: YJ
authors.lastname: Woo
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D054377:Chemokine CXCL12 / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D017076:Computer-Aided Design; D004195:Disease Models, Animal; D015195:Drug Design; D007267:Injections; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D013318:Stroke Volume / Q000187:drug effects; D013718:Tensile Strength; D013997:Time Factors; D014463:Ultrasonography; D016276:Ventricular Function / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D054377:Chemokine CXCL12