Author + information
- Piotr Buszman1,
- Bartlomiej Orlik1,
- Krzysztof Milewski1,
- Mateusz Kachel1,
- Tomasz Roleder2,
- Wojtek Wojakowski3,
- Magdalena Michalak4,
- Adam Janas4,
- Filip Polczyk5,
- Frank Kolodgie6,
- Renu Virmani6 and
- Paweł Buszman1
- 1Center for Cardiovascular Research and Development, American Heart of Poland, Katowice, Poland
- 2Third Division of Cardiology, Medical University of Silesia, Katowice, Poland
- 3Third Department of Cardiology and Structural Heart Diseases, Medical University of Silesia, Katowice, Poland
- 4Center of Cardiovascular Research and Development, American Heart of Poland, Katowice, Poland
- 5Euromedic Ltd, Katowice, Poland
- 6CVPath Institute, Inc., Gaithersburg, Maryland, United States
The preclinical studies of vascular response are limited due to lack of underlying disease. The available cholesterol diet based and genetic atherosclerotic models are not satisfactory due to long breeding, unpredictable lesion formation, low plaque burden and degree of stenosis. We aimed to evaluate the vascular response to local, intramural delivery of human, highly atherogenic lipids in the healthy domestic swine (DS) coronary arteries.
A total of 24 coronary artery segments of 10 DS were enrolled. Following triple, 130% balloon overstretch injury (POBA), segments were assigned to local delivery of 2 ml of oxydated human LDL from apheresis (400 mg/dL, n=9), 0.9% NaCl (control, n=7) or to POBA alone. The solutions were infused with the modified, circumferential micro-needle catheter (Peregrine, ASI) into the vessel wall. Following 28 days, optical coherence tomography (OCT), virtual histology IVUS (VH-IVUS) and NIRS spectroscopy were performed. The vessel segments were harvested for pathological analysis.
The balloon injuries expressed as balloon to artery ratios were comparable among groups and the delivery of solutions was feasible in all cases. At 28 days the plaque burden in IVUS was not different between LDL, control and POBA group respectively (23.4±12% vs. 16.7±9.7%, 16.7±9%; p=0.45) and the %Area Stenosis in OCT was highest in the LDL group (23.6±13 vs. 10.8±7 vs. 8.1±7%; p=0.02). The presence of necrotic core (LDL: 55.5%, Control: 37.5% and POBA: 42.8%; p=0.77) and dense calcium (LDL: 33.3%, Control: 28.5%, POBA: 37.5%; p=0.94) in VH-IVUS were comparable between groups. The Lipid Core Burden index in NIRS was negative in all cases. In histopathology, the injury was comparable between groups (LDL:1.6±0.4, Control: 1.7±0.8, POBA:1.7; p=0.8). In pathology the specimens showed no signs of necrotic core, cholesterol or calcium. The tissue consisted of fibrointimal hyperplasia and proteoglycan-rich matrix in all groups.
Local delivery of saturated human LDL into the coronary wall was feasible, resulted into higher degree of stenosis caused by pathological neointimal thickening. The discrepancy between histopathological findings and VH-IVUS was also noted.
OTHER: Pre-Clinical/First In-Human Studies