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Transplantation:
doi: 10.1097/TP.0000000000000283
Basic and Experimental Research

Sildenafil Citrate in a Donation After Circulatory Death Experimental Model of Renal Ischemia-Reperfusion Injury

Hosgood, Sarah A.1,3; Randle, Lucy V.2; Patel, Meeta1; Watson, Christopher J.2; Bradley, John A.2; Nicholson, Michael L.1

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Abstract

Introduction

Phosphodiesterase-5 inhibitors prevent the breakdown of cyclic guanosine 3′,5′-monophosphate (cGMP) and therefore may be useful in reducing the detrimental effects of ischemia-reperfusion (I/R) injury. The aim of this study was to assess the effects of the phosphodiesterase-5 inhibitor sildenafil, on I/R injury in a porcine model of donation after circulatory death kidney transplantation.

Methods

Kidneys were subjected to 20 min warm ischemia followed by 2 or 18 hr of cold storage (n=6 kidneys per group). After preservation kidneys were reperfused on an ex vivo perfusion system for 3 hr with an oxygenated blood based solution. Kidneys were treated with 1.4 mg/kg sildenafil infused 10 min before and for 20 min after reperfusion (n=6 kidneys per group). Renal function and injury markers were measured throughout reperfusion.

Results

Prolonged cold ischemia (CI) significantly reduced levels of cGMP (2 hr 3.5 [1.5–5.7] vs. 18 hr 1.2 [0.3–2.8] pmol/mL; P=0.010). The administration of sildenafil significantly increased the levels (P=0.047, 0.064). Sildenafil improved the renal blood flow for the first 30 min in the 2-hr group (sildenafil, 81.8 [43.8–101.9] vs. control 40.2 [6.4–76.9] mL/min/100 g; P=0.026) and up to 60 min in the 18-hr group (sildenafil, 67.4 [38.0–87.0] vs. control 36.2 [30.5–50.0] mL/min/100 g; P=0.009) during reperfusion. Renal function was significantly impaired after 18-hr CI (P=0.0.26), and treatment with sildenafil did not improve renal function in the 2-hr (P=0.384) or 18-hr CI (P=0.099) groups.

Conclusion

Sildenafil had a vasodilatory action and increased levels of cGMP but did not affect recovery of renal function or protect against I/R injury.

Copyright © 2014 by Lippincott Williams & Wilkins

 

 

 

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