Abstract 3232: Coronary Revascularization via Percutaneous Intervention (PCI) Improves Cardiac Function by Stimulating Endogenous Cardiac Repair in Swine With Hibernating Myocardium
Background: While coronary revascularization improves function in hibernating myocardium, the time course of recovery is frequently protracted for a year or more and the mechanisms responsible for this are unknown. We tested the hypothesis that the delayed functional recovery reflects ongoing myocyte proliferation through endogenous cardiac repair mechanisms.
Methods: Swine with hibernating myocardium from a chronic LAD occlusion were revascularized by inserting a stent 3 months after instrumentation. We assessed regional flow and function 4 weeks after PCI (n=12) vs. untreated hibernating myocardium (n=7) and normal controls (n=5). Histological analysis quantified myocyte nuclear density. The frequency of myocytes in the growth phase of the cell cycle and cell mitosis were evaluated with Ki-67 and phospho-Histone H3 (pHH3) immunohistochemistry. Myocardial progenitor cells were quantified using the stem cell marker cKit.
Results: PCI led to an increase in resting flow (0.73±0.08 to 0.99±0.11 ml/min/g, p<0.05) and vasodilated flow (0.46±0.10 ml/min/g to 4.40±0.57 ml/min/g, p<0.01). While LAD systolic wall thickening increased from 2.8±0.3 mm in untreated to 4.6±0.4 mm after PCI (p<0.05), it remained depressed below normal (6.1±0.5 mm, p<0.05). Histological analysis (Table⇓) demonstrated that PCI significantly increased Ki-67+ and pHH3+ myocytes in parallel with cKit+ cells. Myocyte nuclear density after PCI was significantly increased from 998±52 to 1406±103 nuclei/mm2 (p<0.01).
Conclusion: These results indicate that coronary revascularization increases myocytes reentering the cell cycle, cKit+ myocardial progenitor cells and myocyte nuclear density. This data suggests that the delayed functional recovery after revascularization may reflect cardiac myocyte regeneration facilitated by alleviating ongoing repetitive myocardial ischemia.