Abstract 17883: Autologous, Non-cell Based Compound Restores Left Ventricular Structure and Function and Amelioration Adverse Remodeling in a Minimally Invasive Large Animal Myocardial Ischemia Model; A Translational Approach
Background: Cell-based myocardial restoration has not penetrated broad clinical practice yet. Here, 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 viability and function.
Methods and Results: Acute myocardial infarction (AMI) was induced in 30 pigs by permanent ligation of the proximal left circumflex coronary artery through a small thoracotomy, and followed by intramyocardial injection of different compounds into both infarct and border areas: saline (control, n=6); hydrogel (n=6); autologous platelets-rich plasma (PRP, n=6); hydrogel mixed with ascorbic acid 50mM, concurrently with intravenous ibuprofen (25mg/kg), allopurinol (25mg/kg), and postoperative oral ibuprofen 25mg/kg x 7 days, allopurinol 25mg/kg x 30 days (cocktail, n=6); combination of PRP and cocktail (whole compound, n=6).
Two months after AMI, the LV in the whole compound group showed less fibrosis (8% vs. 16%), higher fractional area change (36.6±1.1% vs. 26.1± 0.3%, p<0.001) (Fig. 1A), smaller end-diastolic diameter (0.65±0.07 mm/kg vs. 0.77±0.04mm/kg, p<0.05), as compared to the control group. Among treatment groups, the whole compound group had significantly higher dt/dt(max) (at heart rate of 100 bpm) (Fig. 1B), and higher vessel density in the border and infarct areas (Fig.1C,D)(p<0.05).
Conclusions: A combination of angiogenic and anti-inflammatory factors with intramyocardial injection of hydrogel has potential to structurally and functionally improve the injured heart muscle while attenuating adverse cardiac remodelling after AMI. Experiments are under way to carry out the procedure fully endoscopically using a specially manufactured ‘endojector’ device which may render large-scale, and functional myocardial restoration a valid supplement to revascularisation methods, or day-surgery based repetitive application.
- © 2013 by American Heart Association, Inc.