Abstract 4220: Resveratrol Improves Myocardial Perfusion in a Swine Model of Hypercholesterolemia and Chronic Myocardial Ischemia
Introduction: Resveratrol, a polyphenol found in red wine, may provide protection against coronary artery disease. Our hypothesis is that supplemental resveratrol will improve cardiac perfusion in the ischemic territory of swine with hypercholesterolemia and chronic myocardial ischemia.
Methods: Yorkshire swine were made chronically ischemic by placing an ameroid constrictor on the left circumflex artery. Pigs were fed either a normal diet (control, n=7), a hypercholesterol diet (HCC, n=7), or a hypercholesterol diet with supplemental resveratrol (100 mg/Kg/day orally, HCRV, n=7). After 7 weeks, animals underwent cardiac magnetic resonance imaging (CMR) and x-ray coronary angiography prior to sacrifice and tissue harvest.
Results: Regional wall motion analysis using CMR circumferential strain demonstrated a significant decrease in inferolateral regional function from baseline to 7 weeks in HCC swine (−19.1±4% to −11.1±1%, p=0.04). There was no significant change in regional function in HCRV swine from baseline to 7 weeks (p=0.32). Tissue blood flow was 2.8 fold greater in HCRV swine when compared to HCC swine (p=0.04). Endothelial dependent microvascular relaxation response to Substance P (10−7μM) was diminished in HCC swine, but HCRV swine had a relaxation response similar to the control (HCC 38.5±6.7%, HCRV 65.1±10.2%, control 69.6±9.4%, p=0.004). Capillary density (PECAM-1 staining) demonstrated fewer capillaries in both HCC (61±5.4) and HCRV (65±5.4) swine v. control swine (96±17.1, p=0.02). Immunoblotting of HCRV demonstrated a significantly greater expression v. HCC of the following markers of angiogenesis: VEGF (p=0.002), peNOS(ser1177)(p=0.04), NFkB (p=0.004), and pAkt(thr308)(p=0.001). There was no significant difference in the expression of FGF2 between groups (p=0.2).
Conclusion: Supplemental resveratrol in the setting of hypercholesterolemia and chronic myocardial ischemia attenuates regional wall motion abnormalities, preserves endothelial dependent coronary vessel function and upregulates markers of angiogenesis associated with the VEGF signaling pathway. In a clinically relevant swine model of hypercholesterolemia myocardial perfusion in the collateral dependent region was significantly improved.