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Physiology

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Virginia Commonwealth University

Theses and Dissertations

Sildenafil

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Sildenafil Attenuates Ethanol-Induced Cardiomyocyte Injury And Preserves Cardiac Function Through Protein Kinase G-Dependent Signaling, Gregory R. Sturz Apr 2013

Sildenafil Attenuates Ethanol-Induced Cardiomyocyte Injury And Preserves Cardiac Function Through Protein Kinase G-Dependent Signaling, Gregory R. Sturz

Theses and Dissertations

Background: Ethanol is a cardiotoxic substance that damages the heart by increasing apoptosis, free radical formation and calcium overloading. Consequently, there is an increase in cell death leaving fewer functioning myocytes leading to heart failure. Sildenafil is a phosphodiesterase type-5 (PDE-5) inhibitor approved for treatment of erectile dysfunction. Studies from our lab have demonstrated that PDE-5 inhibition reduces myocardial infarct size and attenuates post-ischemic cardiac dysfunction in both ischemia-reperfusion and permanent coronary artery ligation models. Therefore, in the present study, we hypothesized that treatment with sildenafil will prevent cardiotoxicity associated with acute alcohol exposure by reducing myocyte apoptosis and preserving …


Co-Administration Of Sildenafil Potentiates Doxorubicin-Induced Apoptosis In Prostate Cancer: The Role Of Nf-Kappab, Sarah Hassanieh Dec 2008

Co-Administration Of Sildenafil Potentiates Doxorubicin-Induced Apoptosis In Prostate Cancer: The Role Of Nf-Kappab, Sarah Hassanieh

Theses and Dissertations

Our recent studies have shown that that erectile dysfunction (ED) drugs including Sildenafil (Viagra), Vardenafil (Levitra) and Tadalafil (Cialis) enhance killing of several types of cancer cells by anticancer drug, Doxorubicin (DOX). We observed increased cell death by apoptosis in response to the combined treatment with ED drugs and DOX. However, the mechanism of such enhancement of cell death by combined treatment of ED drugs and DOX is not fully understood. Nuclear factor-κB (NF-κB) is an oxidant-sensitive transcription factor that plays a critical role in the immediate-early activation of a multitude of genes that have been documented to play critical …


Long-Term Cardioprotection With Phosphodiesterase-5 Inhibition Against Ischemia-Reperfusion Injury: Role Of Nitric Oxide., Vladimir Paul Daoud Jan 2005

Long-Term Cardioprotection With Phosphodiesterase-5 Inhibition Against Ischemia-Reperfusion Injury: Role Of Nitric Oxide., Vladimir Paul Daoud

Theses and Dissertations

Recent studies have shown that the potent phosphodiesterase-5 (PDE-5) inhibitor, sildenafil citrate, induces a powerful cardioprotective effect against ischemia-reperfusion (I/R) injury in rabbit and mouse hearts. However, the effect of this drug in inducing long-term protection against I/R injury remains unknown. The goal of this study was to identify the duration of the protective window of sildenafil citrate as well as vardenafil, a more potent PDE-5 inhibitor. Rabbits were treated with sildenafil (0.7 mg/kg, iv), vardenafil (0.143 mg/kg), or an equivalent volume of saline. After 24 hrs, 48 hrs, 96 hrs, or 7 days of sildenafil treatment, the hearts were …