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Eur J Vasc Endovasc Surg. 2013 Aug;46(2):242-8. doi: 10.1016/j.ejvs.2013.05.006. Epub 2013 Jun 7.

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

Author information

1
Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany. gaborveres@yahoo.com

Abstract

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.

KEYWORDS:

Endothelium; Ischaemia-reperfusion injury; Storage; Vardenafil; cGMP

PMID:
23751217
DOI:
10.1016/j.ejvs.2013.05.006
[Indexed for MEDLINE]
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