Abstract | AIMS: Cell-based myocardial restoration has not penetrated broad clinical practice yet due to poor cell retention and survival rates. In this study, we attempt a translational, large-scale restorative but minimally invasive approach in the pig, aiming at both structurally stabilizing the left ventricular (LV) wall and enhancing function following ischemic injury. METHODS AND RESULTS: A myocardial infarction (MI) was created by permanent ligation of left circumflex coronary artery through a small lateral thoracotomy. Thirty-six Yorkshire pigs were randomized to receive transthoracic intramyocardial injection into both infarct and border zone areas with different compounds: 1) Hyaluronic acid-based hydrogel; 2) autologous platelet-rich plasma (PRP); 3) ascorbic acid-enriched hydrogel (50 mg/L), combined with IV ibuprofen (25 mg/kg) and allopurinol (25 mg/kg) (cocktail group); 4) PRP and cocktail (full-compound); or 5) saline (control). The latter two groups received daily oral ibuprofen (25 mg/kg) for 7 days and allopurinol (25 mg/kg) for 30 days, postoperatively. Hemodynamic and echocardiographic studies were carried out at baseline, immediately after infarction and at end-point. Eight weeks after MI, the full-compound group had better LV fractional area change, ejection fraction and smaller LV dimensions than the control group. Also, dp/dtmax was significantly higher in the full-compound group when the heart rate increased from 100 bpm to 160bpm in stress tests. Blood vessel density was higher in the full-compound group, compared to the other treatment groups. CONCLUSIONS: A combination of PRP, anti-oxidant and anti-inflammatory factors with intramyocardial injection of hydrogel has the potential to structurally and functionally improve the injured heart muscle while attenuating adverse cardiac remodeling after acute myocardial infarction.
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Authors | Thang Duc Vu, Shripad N Pal, Lian-Kah Ti, Eliana C Martinez, Abdul Jalil Rufaihah, Lieng H Ling, Chuen-Neng Lee, Arthur Mark Richards, Theo Kofidis |
Journal | Biomaterials
(Biomaterials)
Vol. 45
Pg. 27-35
(Mar 2015)
ISSN: 1878-5905 [Electronic] Netherlands |
PMID | 25662492
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Ltd. All rights reserved. |
Chemical References |
- Hydrogel, Polyethylene Glycol Dimethacrylate
- Collagen
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Topics |
- Animals
- Cicatrix
(pathology)
- Collagen
(metabolism)
- Diastole
(drug effects)
- Female
- Heart Ventricles
(drug effects, pathology, physiopathology)
- Hydrogel, Polyethylene Glycol Dimethacrylate
(pharmacology)
- Injections
- Myocardial Contraction
(drug effects)
- Myocardial Infarction
(diagnostic imaging, physiopathology, therapy)
- Myocardium
(pathology)
- Neovascularization, Physiologic
(drug effects)
- Platelet-Rich Plasma
(metabolism)
- Sus scrofa
- Translational Research, Biomedical
- Transplantation, Autologous
- Ultrasonography
- Ventricular Function, Left
(drug effects)
- Ventricular Remodeling
(drug effects)
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