Post-ischaemic angiogenic therapy using in vivo prevascularized ascorbic acid-enriched myocardial artificial grafts improves heart function in a rat model

Angiogenesis plays a key role in post-ischaemic myocardial repair. We hypothesized that epicardial implantation of an ascorbic acid (AA)-enriched myocardial artificial graft (MAG), which has been prevascularized in the recipients' own body, promotes restoration of the ischaemic heart. Gelatin patches were seeded with GFP-luciferase-expressing rat cardiomyoblasts and enriched with 5 μm AA. Grafts were prevascularized in vivo for 3days, using a renal pouch model in rats. The MAG patch was then implanted into the same rat's ischaemic heart following myocardial infarction (MI). MAG-treated animals (MAG group, n=6) were compared to untreated infarcted animals as injury controls (MI group, n=6) and sham-operated rats as healthy controls (healthy group, n=7). In vivo bioluminescence imaging indicated a decrease in donor cell survival by 83% during the first week post-implantation. Echocardiographic and haemodynamic assessment 4weeks after MI revealed that MAG treatment attenuated left ventricular (LV) remodelling (LV end-systolic volume, 0.31±0.13 vs 0.81±0.01ml, p<0.05; LV end-diastolic volume 0.79±0.33 vs 1.83±0.26ml, p<0.076) and preserved LV wall thickness (0.21±0.03 vs 0.09±0.005cm, p<0.05) compared to the MI group. Cardiac output was higher in MAG than MI (51.59±6.5 vs 25.06±4.24ml/min, p<0.01) and comparable to healthy rats (47.08±1.9ml/min). Histology showed decreased fibrosis, and a seven-fold increase in blood vessel density in the scar area of MAG compared to MI group (15.3±1.1 vs 2.1±0.3 blood vessels/hpf, p<0.0001). Implantation of AA-enriched prevascularized grafts enhanced vascularity in ischaemic rat hearts, attenuated LV remodelling and preserved LV function.