Addition of vardenafil into storage solution protects the endothelium in a hypoxia-reoxygenation model

Objective - Based upon the well known protective effect of intracellular cyclic guanosine monophosphate (cGMP) accumulation, we tested the hypothesis that storage solution enriched with optimal concentration of the phosphodiestherase-5 inhibitor vardenafil could provide better protection of vascular...

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Main Authors: Veres, Gábor (Author) , Hegedűs, Péter (Author) , Barnucz, Enikő (Author) , Zöller, Raphael (Author) , Radovits, Tamás (Author) , Korkmaz-İçöz, Sevil (Author) , Kolonics, F. (Author) , Weymann, Alexander (Author) , Karck, Matthias (Author) , Szabó, Gábor (Author)
Format: Article (Journal)
Language:English
Published: 7 June 2013
In: European journal of vascular and endovascular surgery
Year: 2013, Volume: 46, Issue: 2, Pages: 242-248
ISSN:1532-2165
DOI:10.1016/j.ejvs.2013.05.006
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ejvs.2013.05.006
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1078588413003225
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Author Notes:G. Veres, P. Hegedűs, E. Barnucz, R. Zöller, T. Radovits, S. Korkmaz, F. Kolonics, A. Weymann, M. Karck, G. Szabó
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Summary:Objective - Based upon the well known protective effect of intracellular cyclic guanosine monophosphate (cGMP) accumulation, we tested the hypothesis that storage solution enriched with optimal concentration of the phosphodiestherase-5 inhibitor vardenafil could provide better protection of vascular grafts against reperfusion injury after long-term cold ischaemic storage. - Methods - Isolated thoracic aorta obtained from rats underwent 24-h cold ischaemic preservation in physiological saline or vardenafil (10−11 M)-supplemented saline solution. Reperfusion injury was simulated by hypochlorite (200 μM) exposure for 30 minutes. Endothelium-dependent vasorelaxation was assessed, and histopathological and molecular-biological examination of the aortic tissue were performed. - Results - Compared with the control group, the saline group showed significantly attenuated endothelium-dependent maximal relaxation (Rmax) to acetylcholine after hypoxia-reoxygenation, which was significantly improved by vardenafil supplementation (Rmax control: 98 ± 1%; saline: 48 ± 6%; vardenafil: 75 ± 4%; p < .05). Vardenafil treatment significantly reduced DNA strand breaks (control: 10.6 ± 6.2%; saline: 72.5 ± 4.0%; vardenafil: 14.2 ± 5.2%; p < .05) and increased cGMP score in the aortic wall (control: 8.2 ± 0.6; saline: 4.5 ± 0.3; vardenafil: 6.7 ± 0.6; p < .05). - Conclusions - Our results support the view that impairment of intracellular cGMP signalling plays a role in the pathogenesis of the endothelial dysfunction induced by cold storage warm reperfusion, which can be effectively reversed by pharmacological phosphodiesterase-5 inhibition.
Item Description:Gesehen am 24.02.2022
Physical Description:Online Resource
ISSN:1532-2165
DOI:10.1016/j.ejvs.2013.05.006