Abstract 10834: Post-Ischemic Angiogenic Therapy Using In Vivo Pre-Vascularized Ascorbic Acid-Enriched Myocardial Artificial Grafts Improves Heart Function in a Rat Model
Introduction: Angiogenesis plays a key role in post-ischemic myocardial repair and remains a challenge in myocardial tissue engineering. We assessed the hypothesis that ascorbic acid (AA)-enriched myocardial artificial grafts (MAG) which have been pre-vascularized in the recipients' own body promote restoration of the ischemic heart.
Methods and Results: MAGs were constructed by seeding a macroporous gelatin patch with a solution containing 5 μmol-L AA and rat H9C2 cardiomyoblasts-expressing GFP and luciferase. Next, grafts were pre-vascularized in vivo for 3 days using a renal pouch model in Wistar rats. MAG's restorative potential was assessed by implanting the pre-vascularized patch into the ischemic heart of the same animal following left anterior descending coronary artery ligation (n=6). MI animals without treatment were used as injury controls (n=6), and sham thoracotomy animals were included as healthy (n=7). In vivo donor cell survival in the MAG group was assessed by bioluminescence imaging at days 1, 7 and 14 post-implantation. A decrease in donor cell photon emission by 80%; was found during the first week post-implantation (P<0.0001). Echocardiography and hemodynamic assessments four weeks after MI revealed that MAG treatment attenuated left ventricle (LV) remodeling (LV end-systolic volume 0.31 ± 0.13 vs. 0.81 ± 0.01 ml, P<0.05; LV end-diastolic volume 0.79 ± 0.33 vs. 1.83 ± 0.26 ml, P<0.076), and preserved LV wall thickness (0.21 ± 0.03 vs. 0.09 ± 0.005 cm, P<0.05) compared to MI. The percent change in LV cross-sectional area between diastole and systole (FAC) was 33.50 ± 2.02%; in MI, 42.80 ± 5.36%; in MAG-treated, and 57.0 ± 9.29%; in healthy animals (P<0.05, MI vs. healthy). Cardiac output was significantly higher in MAG-treated rats compared to MI (41.4 ± 4.6 vs. 33.1 ± 2.6 ml·min −1, P<0.05) and was comparable to healthy (40.2 ± 1.9 ml·min−1). Histology revealed decreased fibrosis, as well as a 7-fold increase in blood vessel density in the scar area of MAG-treated hearts compared to MI hearts (15.28 ± 1.1 vs. 2.06 ± 0.3 blood vessels/hpf, P<0.0001).
Conclusions: Implantation of AA-enriched-prevascularized grafts induced a robust angiogenic response in ischemic rat hearts, decreased LV remodeling and preserved LV function.
- © 2010 by American Heart Association, Inc.