Thang Duc Vu1, Shripad N Pal1, Lian-Kah Ti2, Eliana C Martinez3, Abdul Jalil Rufaihah1, Lieng H Ling4, Chuen-Neng Lee5, Arthur Mark Richards4, Theo Kofidis6. 1. Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 2. Department of Anesthesia, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 3. Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 4. Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 5. Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiac, Thoracic and Vascular Surgery, National University Health System, Singapore. 6. Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiac, Thoracic and Vascular Surgery, National University Health System, Singapore. Electronic address: surtk@nus.edu.sg.
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.
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.
Authors: Negar Faramarzi; Iman K Yazdi; Mahboubeh Nabavinia; Andrea Gemma; Adele Fanelli; Andrea Caizzone; Leon M Ptaszek; Indranil Sinha; Ali Khademhosseini; Jeremy N Ruskin; Ali Tamayol Journal: Adv Healthc Mater Date: 2018-04-16 Impact factor: 9.933
Authors: Elisa Garbayo; Juan José Gavira; Manuel Garcia de Yebenes; Beatriz Pelacho; Gloria Abizanda; Hugo Lana; María José Blanco-Prieto; Felipe Prosper Journal: Sci Rep Date: 2016-05-17 Impact factor: 4.379