Abstract 16151: Local Delivery of Zoledronate Attenuates the Aortic Valve Calcification in an Experimental Model of Aortic Stenosis
Introduction: The inhibition of vascular calcifications has been successfully tested by local delivery of bisphosphonates
Hypothesis: The aim of the present study was to evaluate the safety and effectiveness of local delivery of the bisphosphonates on inhibition of calcification in an experimental model of aortic stenosis .
Methods: Eight New Zealand rabbits were placed on vitamin D enriched atherogenic diet for 3 weeks. At that time a cardiac ultrasound was performed to assess the aortic stenosis and aortic calcification of the aortic valve and was followed by local delivery of a mixture containing 500 μg/l zoledronate on the cusps of the aortic valve (AV), by a dedicated balloon catheter. PET/CT imaging was performed in all rabbits a day before the local delivery of zoledronate and at 28 days after local drug delivery. 18F-NaF (mean administered dose of F18 NaF was 142.4 MBq, SD: 9.5 MBq) in a standard volume of 1ml was injected intravenously. Following a 45min uptake time, a static PET acquisition was obtained over a period of 20min. PET imaging was preceded by CT for attenuation correction and anatomical localization of the PET images. The progression of calcification was assessed by calculating the difference in SUVmax, SUVmean, TBRmax and TBR mean at baseline and at follow up both for AV and ascending aorta (AA). After the second PET/CT examination all animals were sacrificed and all AVs were analyzed by histology. The difference between the extent of calcification between the proximal part of the aorta and the cusps was calculated and assigned as ΔC.
Results: At baseline, all animals developed AV stenosis with severe calcification. SUVmax and SUVmean showed an attenuation of calcification in AV compared to AA (0.34±0.23 vs 0.11±0.20, p=0.09 for SUVmax and 0.21±0.55 vs 0.19±0.19, p=0.90 for SUVmean.). TBR max and TBR mean showed a decrease in calcification in the AV compared to the AA (0.17±0.55 vs -0.24±0.53, p=0.21 for TBR max and 0.78±0.74 vs -0.12±0.50, p=0.032 for TBR mean). Histology confirmed the findings of PET/CT. The calcification at the AA was more extended compared to the calcification observed at the AV (6.72 vs 3.36, p<0.001)
Conclusions: Local delivery of zoledronate attenuated the calcification process in an experimental model of aortic stenosis.
Author Disclosures: A. Synetos: None. K. Toutouzas: None. I. Cutajar: None. M. Drakopoulou: None. K. Stathogiannis: None. G. Agrogiannis: None. A. Papalois: None. E. Patsouris: None. D. Cokkinos: None. D. Tousoulis: None.
- © 2016 by American Heart Association, Inc.