The Nephroprotective Effects of Sildenafil Citrate Against Contrast Induced Nephropathy : Assessing Efficacy and Determining Appropriate Dosage in Rabbits
Carey, Edward Grant
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Contrast induced nephropathy (CIN) is a clinical condition often exhibited by patients undergoing cardiovascular procedures requiring the visualization of blood vessels. To enhance the visibility of blood vessels, radiocontrast agents, known to be relatively nephrotoxic, are administered to patients. Patients with preexisting conditions that impair kidney function, such as chronic kidney disease, are at a particularly high risk of renal damage. Defined as a relative (≥25%) or absolute (≥0.5 mg/dl) increase in blood serum creatinine concentration, CIN accounts for substantial morbidity and mortality, as well as secondary costs to healthcare institutions. One aim of this study is to examine the potential for sildenafil citrate, a phosphodiesterase type 5 inhibitor, to curtail the nephrotoxic effects of radiocontrast agents. We exposed New Zealand white rabbits to radiocontrast agent, with half of the animals receiving sildenafil citrate treatment and the remainder receiving a placebo. Using serum creatinine analysis and histopatholgical examination, we offer motivation for future studies to administer multiple doses of sildenafil citrate continually before, during and after radiocontrast agent exposure. A further aim of this study was to determine an appropriate radiocontrast agent dosing protocol for a rabbit CIN model. Using varying doses of radiocontrast agent, we found that an optimal level of radiocontrast agent dose for the investigation of CIN in rabbits is approximately 5.0 mg Ioxilan/kg (I/kg). We conclude that sildenafil citrate is a potential prophylactic option to prevent CIN, though further research using an appropriate radiocontrast agent and sildenafil citrate dosing protocol is necessary to substantiate these findings.