Intravenous Sildenafil as a Preconditioning Drug Against Hemodynamic Consequences of Warm Ischemia-Reperfusion on the Kidney
2011; Lippincott Williams & Wilkins; Volume: 186; Issue: 1 Linguagem: Inglês
10.1016/j.juro.2011.03.036
ISSN1527-3792
AutoresE. Lledó‐García, D. Subirá-Ríos, Gabriel Ogaya‐Pinies, A. Tejedor-Jorge, Juan Francisco del Cañizo-López, C. Hernández Fernández,
Tópico(s)Cardiac Arrest and Resuscitation
ResumoNo AccessJournal of UrologyInvestigative Urology1 Jul 2011Intravenous Sildenafil as a Preconditioning Drug Against Hemodynamic Consequences of Warm Ischemia-Reperfusion on the Kidney Enrique Lledo-Garcia, David Subira-Rios, Gabriel Ogaya-Pinies, Alberto Tejedor-Jorge, Juan Francisco Del Cañizo-Lopez, and Carlos Hernandez-Fernandez Enrique Lledo-GarciaEnrique Lledo-Garcia Urology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain Experimental Renal Preservation Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain More articles by this author , David Subira-RiosDavid Subira-Rios Urology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain Experimental Renal Preservation Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain More articles by this author , Gabriel Ogaya-PiniesGabriel Ogaya-Pinies Experimental Renal Preservation Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain More articles by this author , Alberto Tejedor-JorgeAlberto Tejedor-Jorge Experimental Nephrology Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain More articles by this author , Juan Francisco Del Cañizo-LopezJuan Francisco Del Cañizo-Lopez Experimental Medicine Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain Artificial Circulatory Laboratory, Hospital General Universitario Gregorio Marañón, Madrid, Spain More articles by this author , and Carlos Hernandez-FernandezCarlos Hernandez-Fernandez Urology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.03.036AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We designed an experimental model of renal ischemia-reperfusion to evaluate the preemptive effect of intravenous sildenafil according to the dose administered (0.7 vs 1.4 mg/kg) and the time of administration (30 minutes before ischemia or during ischemia). Materials and Methods: A total of 20 minipigs were divided into groups of 4 each, including group 1—control, group 2—sildenafil 0.7 mg/kg intravenously 30 minutes before vascular clamping, group 3—sildenafil 0.7 mg/kg intravenously during warm ischemia, group 4—sildenafil 1.4 mg/kg intravenously 30 minutes before vascular clamping and group 5—sildenafil 1.4 mg/kg intravenously during warm ischemia. The ischemia-reperfusion model was applied using laparotomy and right kidney vascular clamping for 30 minutes, followed by unclamping and reperfusion for 45 minutes. Renal vascular flow and systemic mean arterial pressure were recorded for 45 minutes after unclamping. Mean values were compared using Student t test with significance considered at p <0.05. Results: Sildenafil led to a decrease in arterial pressure compared to that in controls, especially at the dose of 1.4 vs 0.7 mg/kg, including 113.77, 109.76, 106.12, 97.41 and 82.85 mm Hg in groups 1 to 5, respectively. Renal vascular flow was significantly higher in groups 2 and 3 than in groups 1, 4 and 5 (112.82 and 111.33 vs 88.25, 87.91 and 84.37 ml per minute, respectively, p = 0.000). Conclusions: The effect of intravenous sildenafil as a preemptive drug against the hemodynamic effects of renal ischemia-reperfusion is dose dependent. The 0.7 mg/kg dose significantly increased reperfusion renal vascular flow with a small decrease in arterial pressure compared to the 1.4 mg/kg dose. References 1 : Anti-vimentin antibody detection in recipients of heart-beating and non-heart-beating donor kidneys. Transplant Proc2005; 37: 3269. Google Scholar 2 : Nitroglycerin reperfusion reduces ischemia-reperfusion injury in non-heart-beating donor lungs. J Heart Lung Transplant2006; 25: 110. Google Scholar 3 : Pharmacology of erectile dysfunction in man. Pharmacol Ther2006; 111: 400. Google Scholar 4 : Inhaled nitric oxide reduces ischemia-reperfusion injury in rat lungs from non-heart-beating donors. J Thorac Cardiovasc Surg2006; 132: 132. Google Scholar 5 : Pharmacological preconditioning with sildenafil: basic mechanisms and clinical implications. Vasc Pharmacol2005; 42: 219. Google Scholar 6 : Sildenafil as a protecting drug for warm ischemic kidney transplants: experimental results. J Urol2009; 182: 1222. Link, Google Scholar 7 : The Non-Heart Beating Donor, A New Source for Kidney Transplantation: Clinical and Experimental Studies. Maastricht: Universitaire Pers Maastricht1995. Google Scholar 8 : Mechanism of direct relaxant effect of sildenafil, tadalafil and vardenafil on corpus cavernosum. Eur J Pharmacol2006; 541: 184. Google Scholar 9 : Sildenafil: emerging cardiovascular indications. Annals Thorac Surg2004; 78: 1496. Google Scholar 10 : Vascular effects of sildenafil in hypertensive cardiac transplant recipients. Am J Hypertens2003; 16: 874. Google Scholar 11 : Traitement de l'hypertension artérielle pulmonaire de l'enfant. Arch Pédiatr2004; 11: 945. Google Scholar 12 : Pharmacokinetic and hemodynamic responses to oral sildenafil during invasive testing in children with pulmonary hypertension. J Am Coll Cardiol2010; 55: 1456. Google Scholar © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byAtala A (2018) Re: Carvedilol Efficiently Protects Kidneys without Affecting the Antitumor Efficacy of Cisplatin in MiceJournal of Urology, VOL. 192, NO. 2, (614-614), Online publication date: 1-Aug-2014. Volume 186Issue 1July 2011Page: 331-333 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.Keywordssildenafilkidney transplantationwarm ischemiakidneyreperfusionAcknowledgmentsPfizer provided sildenafil as a pure substance.MetricsAuthor Information Enrique Lledo-Garcia Urology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain Experimental Renal Preservation Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain More articles by this author David Subira-Rios Urology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain Experimental Renal Preservation Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain More articles by this author Gabriel Ogaya-Pinies Experimental Renal Preservation Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain More articles by this author Alberto Tejedor-Jorge Experimental Nephrology Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain More articles by this author Juan Francisco Del Cañizo-Lopez Experimental Medicine Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain Artificial Circulatory Laboratory, Hospital General Universitario Gregorio Marañón, Madrid, Spain More articles by this author Carlos Hernandez-Fernandez Urology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain More articles by this author Expand All Advertisement PDF downloadLoading ...
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