In-vivo Acute Ureteral Dilation using Electromotive Drug Administration (EMDA) in the Porcine Ureter "Presentation"

May 6, 2024

Bruce Gao presented research on Electromotive Drug Administration in the Porcine Ureter, demonstrating its potential to enhance drug delivery and ureteral distensibility, offering new insights into acute ureteral dilation.


Bruce M. Gao, MD, Urologist, University of California Irvine, Irvine, CA


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Bruce M. Gao: Hello, viewers. I'm thrilled to present our findings on Electromotive Drug Administration and the Porcine Ureter for acute ureteral dilation.

Drugs can be delivered in a wide variety of ways. Each route has their own benefits and drawbacks. In intravenous delivery, drugs often have a shorter duration of action and may exert systemic side effects. In oral delivery, drugs may change form when processed through the liver, or undergo variable absorption by the gut. As urologists, we're familiar with intravascular delivery, such as with BCG. Absorption here is limited by the impermeability of the tight junctions within the urothelium. Within the ureter, there are additional considerations. Firstly, the oral and intravenous route provides for uncertain specific delivery into the ureteral wall. Additionally, it is more difficult to administer drug locally due to requirement for retrograde infusion. It is also difficult to maintain the drug in the same location, due to urine production and ureteral peristalsis. Finally, the impermeability of the urothelium in the ureter also limits drug absorption.

To augment localized drug delivery, we have been researching Electromotive Drug Administration, or EMDA. EMDA enhances drug delivery with a small electrical current. EMDA has been used in the bladder, skin, eye, and the breast, and as urologists, we're likely familiar with EMDA and mitomycin C in the bladder.

Given the challenges of delivering drugs locally to the upper urinary tract, we sought to devise a method to optimize drug delivery within the ureter with EMDA, with a goal towards acutely increasing urethral distensibility to enhance passage of a larger urethral access sheet.

We created a novel EMDA catheter for this. The EMDA catheter is distally fenestrated for 20 centimeters, and the silver wire is exposed distally to match. Once the wire is placed in the catheter, a three-way adapter allows for the simultaneous addition of drugs and electrical current, along with the CVP line, to maintain low intrarenal pressure.

For proof of concept, we conducted in vivo porcine studies with methylene blue and EMDA. As you can see here, the left ureter with EMDA shows deep blue staining, whereas the right ureter without EMDA only shows faint staining. On light microscopy, there is dense staining of methylene blue with EMDA to the lamina propria layer, and only patchy faint staining without EMDA, as shown by the arrow here.

Given our initial success, we sought to apply this novel drug delivery method to three smooth muscle relaxants within the porcine ureter to assess their impact on dilation.

18 juvenile female Yorkshire pigs were enrolled for study. The pigs were positioned supine after anesthesia, and bilateral super stiff wires were placed.

The baseline diameter of both ureters was determined by sequential passage of urethral dilators using a proprietary UC Irvine force sensor. Dilators were passed at no more than three and a half Newtons of force each time.

EMDA catheters were positioned fluoroscopically in the ureter, and bladder drainage was maintained with a 12 French foley catheter. A CVP line for drug administration was set at 40 centimeters of water. An EMDA wire was passed into each catheter. A grounding pad was placed on the treatment side.

On one side, we am administered 0.9% sodium fluoride without EMDA as our control. And on the other side, we am administered our drug of choice with EMDA, at 10 milliamps for 20 minutes. The laterality for each treatment was randomized.

Ureteral diameter was reassessed immediately following EMDA treatment. Ureteroscopy was performed to exclude splitting of the ureter, which would increase its diameter as a false positive.

Dilator progression was scored in single units, one unit for each location of the ureter passed, distal, mid, and proximal. Therefore, each one French increase in dilator size works out to three units. We then conducted a non-parametric paired analysis of the data.

Here are the results. The graph shows a change in dilation score, whereby a positive number is a size increase, and a negative number is a size decrease. As you can see, EMDA with alfuzosin demonstrate a significant increase in dilation compared to control.

As you can see on the next set of bars, EMDA with isoproterenol and aminophylline did not result in dilation.

To prove that EMDA was indeed working, additional in vivo experiments were conducted to compare two ureters, one ureter with alfuzosin alone, and another ureter with alfuzosin and EMDA. MALDI mass spec, which can determine exact drug concentration location within biological tissue demonstrates a nine times higher concentration of alfuzosin in ureters when EMDA is applied.

MALDI imaging is currently being further analyzed to identify exact alfuzosin concentration and location within the ureter. Additional studies regarding EMDA and other drugs such as chemotherapy are pending.

In conclusion, ureteral infusion of alfuzosin using electromotive drug administration resulted in drug deposition deep into the ureteral wall and significantly increased porcine ureteral distensibility.

Thank you.