Presented by: Bruce Gao MD
University of California, Irvine. Department of Urology

Introduction

Electromotive drug administration (EMDA) is a technique used to amplify drug delivery to targeted tissues. Previously, we presented the safety and feasibility of using EMDA to drive a positively charged, small molecule into the ureteral wall. Herein we investigated the safety and efficacy of EMDA in the renal pelvis during an upper tract infusion of methylene blue. To the best of our knowledge, this is the first application of EMDA in the renal pelvis.

Materials

In a female Yorkshire pig under general anesthesia, a midline incision was made, and the retroperitoneal space was accessed. The proximal ureters were sharply transected two inches distal to the ureteropelvic junction. An 8 Fr dual lumen catheter and a 24 AWG silver wire insulated by passage through a 5 Fr catheter fenestrated in three rows (0.3 mm each) in its 5 cm distal end were inserted into both renal pelvises. The ureteral tissue around the catheter was secured with a 2-0 silk suture, creating a water-tight seal around the catheter. A dispersive pad was affixed to the flank on the experimental side and connected to the negative electrode of the EMDA generator (Physion® Mini 30N2). Methylene blue (0.1%), a positively charged, water-soluble stain with a molecular weight of 334 Daltons, was infused via the dual lumen catheter using a drug infusion pump at a rate of 5 ml/min; one lumen of the 8Fr catheter was left open to gravity drainage.  A positive pulsed electrical current of 4 mA was applied for 20 minutes in the experimental ureter. The same infusion was performed on the contralateral side; however, the silver wire was not activated.  The pig was euthanized, and both kidneys were excised and frozen for subsequent histopathological analysis.

Results

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The experimental renal pelvis exhibited dense staining on a macroscopic level. Under H&E staining, both pelvises displayed slight denudation of the urothelial cells due to the freezing of the specimens; no injury was found in the deeper tissues. Frozen sections of the experimental renal pelvis revealed a dense and diffuse penetration of methylene blue into the urothelium and lamina propria. Conversely, the control kidney showed faint methylene blue staining of the urothelium without deeper penetration.

Conclusion

In the porcine renal pelvis, EMDA increased the penetration of a small water-soluble charged molecule into the urothelium and lamina propria.  

Funding

None

Lead Authors

Ralph V. Clayman, MD
University of California, Irvine. Department of Urology

Co-Authors

Seyed Hossein Hosseini Sharifi, MD
University of California, Irvine. Department of Urology

Zachary E. Tano, Md
University of California, Irvine. Department of Urology

Seyed Amiryaghoub M. Lavasani, Junior research assistant
University of California, Irvine. Department of Urology

Yi Xi Wu, PHD
University of California, Irvine. Department of Urology

Seyed Amirvala Saadat, Junior researcher
Department of Urology, University of California, Irvine, CA, USA

Sohrab Naushad Ali, MD
University of California, Irvine. Department of Urology

Erika Martinez-Carcamo, Lab Manager
University of California, Irvine. Department of Urology

Mahra Nourbakhsh, MD
University of California, Irvine. Department of Pathology

Pengbo Jiang, MD
University of California, Irvine. Department of Urology

Roshan M. Patel, MD
University of California, Irvine. Department of Urology

Michael Daneshvar, MD
University of California, Irvine. Department of Urology

Jaime Landman, MD
University of California, Irvine. Department of Urology

Ralph V. Clayman, MD
University of California, Irvine. Department of Urology