Sildenafil as a protecting drug for warm ischemic kidney transplants: experimental results.
OBJECTIVE
In an experimental model we studied the protective effects of the phosphodiesterase-5 inhibitor sildenafil on kidney grafts autotransplanted after 45 minutes of warm ischemia by vascular clamping, nephrectomy and 60 minutes of isolated hypothermic pump perfusion.


METHODS
A total of 14 laboratory minipigs were divided into group 1-7 administered 100 mg sildenafil orally 1.5 hours preoperatively and group 2-7 in which no sildenafil was given. Right single nephrectomy was completed after 45 minutes of warm ischemia by complete vascular clamping. Before autotransplantation all kidneys underwent 60 minutes of hypothermic pulsatile perfusion. Renal flow, arterial pressure and renal vascular resistance were recorded in real time for 60 minutes after autotransplantation. Nitric oxide levels were determined in blood samples from the renal vein at predefined intervals. Optical and electronic microscopy was done in all organs at the end of the procedure.


RESULTS
In group 1 vs 2 renal vascular flow was significantly higher (155.30 vs 29.04 ml per minute per 100 gm) and renal vascular resistance was significantly lower (0.59 vs 3.10 mm Hg/ml per minute, each p <0.01). No significant differences were observed in systemic arterial pressure between groups 1 and 2 (84.08 and 84.65 mm Hg, respectively, p >0.05). Nitric oxide levels were significantly higher for all periods in group 1 (49.94 vs 16.85 muM, p <0.01). No significant differences were observed in histological studies, although endothelial cell structure was better preserved in the sildenafil group.


CONCLUSIONS
To our knowledge our study suggests for the first time in the literature a positive effect of sildenafil in the immediate posttransplantation outcome of warm ischemic kidneys without secondary systemic effects.
Lledó-García
Enrique
E
Urology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Subirá-Ríos
David
D
Rodríguez-Martínez
Daniel
D
Dulín
Elena
E
Alvarez-Fernández
Emilio
E
Hernández-Fernández
Carlos
C
del Cañizo-López
Juan Francisco
JF
D000818:Animals; D004195:Disease Models, Animal; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D016030:Kidney Transplantation; D009926:Organ Preservation; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D015427:Reperfusion Injury; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D013552:Swine; D019737:Transplants; D014665:Vasodilator Agents / Q000494:pharmacology*; D052096:Warm Ischemia
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate