Τόμος 20 (2006) – Τεύχος 2 – Άρθρο 54 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Διεθνής Έκδοση – Volume 20 (2006) – Issue 2 – Article 54 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-International Edition

Title Thrombin augments therapeutic angiogenesis in the rabbit hindlimb ischemia model: a comparative angiographic and dynamic computed tomography study
Authors Konstantinos Katsanos¹, Nikos Tsopanoglou², Dimitrios Karnabatidis¹, George C. Kagadis³, Athanasios Diamantopoulos¹, Nikolaos Siasos, John Maroulis, Panagiota Ravazoula, George Nikiforidis³ and Dimitrios Siablis¹

Departments of 1. Radiology, 2. Pharmacology, 3. Medical Physics, 4. Surgery and 5. Pathology, School of Medicine, University of Patras, Rio 26500, Greece

Citation Katsanos, K., Tsopanoglou, N., Karnabatidis, D., Kagadis, G.C., Diamantopoulos, A. et al: Thrombin augments therapeutic angiogenesis in the rabbit hindlimb ischemia model: a comparative angiographic and dynamic computed tomography study, Epitheorese Klin. Farmakol. Farmakokinet. 20(2): 210-212 (2006)
Publication Date Accepted for publication: 19-20 May 2006
Full Text Language English
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Keywords Thrombin, ischemia, therapeutic  angiogenesis, digital angiography,  dynamic computed tomography.
Other Terms review article
Summary Purpose: To evaluate and compare the angiogenic and arteriogenic capacity of thrombin with two well-established angiogenic factors (bFGF, VEGF) in the hindlimb ischemia model of the New Zealand White rabbit. Bilateral hindlimb ischemia was invoked by surgical excision of the femoral artery. On day 20, after quiescence of endogenous angiogenesis, thrombin (500 IU or 1,500 IU or 5,000 IU) or VEGF (1 µg or 3 µg or 10 µg) or bFGF (1 µg or 3 µg or 10 µg) were intramuscularly injected in the medial thigh of one ischemic hindlimb per rabbit (n=7 in each group), while the contralateral limbs were injected with equal volume of normal saline and served as the control groups. On day 40, intraarterial DSA followed by computerized quantitative analysis of the depicted vasculature and dynamic-CT at the level of the saphenous artery were performed. Quantitative DSA detected a significantly in- creased total area of large collaterals (d>500 µm) only in the thrombin 5,000 IU group (p<0.05). Post-processing of dynamic-CT studies documented increased peak enhancement values and shorter time-to-peak periods in all high-dose groups as compared to control hindlimbs. However, the observed difference proved to be statistically significant (p<0.05) only in the thrombin 5,000 IU group. Histopathology of the adductor muscle in the medial thigh documented a significantly increased neovascularization outcome only in the thrombin 5,000 IU group (p<0.05). Thrombin augments therapeutic angiogenesis and ischemic tissue reperfusion and seems to outperform bFGF and VEGF in establishing new vessel conduits with a developed tunica media in the rabbit model of hindlimb ischemia.
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