Aymon Ali: Hi there. My name is Aymon Ali. I'm an endourology fellow at the University of California Irvine, and I'm presenting our investigation into the effect of intravenous administration of a Rho-kinase inhibitor, namely Fasudil, on ureteral distensibility. Ureteral access remains a rate limiting step in retrograde intrarenal surgery, with reported ureteral injury rates as high as 46%. The Rho-kinase, or ROCK pathway, plays a central role in maintaining ureteral smooth muscle tone by inhibiting myosin light chain phosphatates. Fasudil is a selective ROCK inhibitor that has been clinically approved in Japan and China since 1995 for cerebral vasospasm with a well characterized safety profile. We hypothesized that systemic ROCK inhibition could pharmacologically relax the ureter and increase its distensibility.

To investigate this, 16 female Yorkshire pigs were allocated to a treatment arm of 10 animals, 20 ureters, and a control arm of six animals with 12 ureters. We performed bilateral baseline ureteral sizing by sequentially passing urethral dilators in two French increments at a predetermined safe insertion force of 3.5 newtons, measured with the UCI electronic force sensor.

The treatment arm received 80 to 160 milligrams of intravenous Fasudil and 100 milliliters of 50% dextrose. The control arm received the dextrose vehicle alone. Sizing was repeated at 15 and 30 minutes post-infusion, with serum drawn at each time point for pharmacokinetic and concentration analysis. Intravenous Fasudil produced a statistically significant increase in maximum dilator size, from a baseline of 13.88 French to 15.5 French at 30 minutes post-infusion, with a mean delta of 1.63 French representing approximately a dilator size increase.

The control arm, by contrast, showed no significant change. We saw no statistical difference between the 15 and 30-minute time points in the treatment arm, suggesting the effect is established early. Interestingly, neither serum Fasudil nor its active metabolite, Hydroxyfasudil, correlated with the magnitude of dilation, which raises questions about local versus systemic pharmacodynamics that we plan to explore in feature work.

Two animals were excluded from the study due to pulse grade three or higher injuries. In all instances in these animals, the insertion force inadvertently exceeded six newtons.

In conclusion, intravenous administration of Fasudil produced a clinically meaningful 1.63 French increase in ureteral distensibility in our porcine model. Given that even a one to two French gain can be the difference between a successful and failed ureteral access, ROCK inhibition represents a promising adjunct to retrograde intrarenal surgery and warrants- Thank you.