Presentation Authors: Laith Alzweri*, New Orleans, LA, Serap Gur, New Orleans, Turkey, Sudha Talwar, Amit Reddy, Suresh Sikka, Omer Raheem, Asim Abdel-Mageed, Wayne Hellstrom, New Orleans, LA
Introduction: Collagenase Clostridium histolyticum (CCH) (XiaflexÂ®; Endo, Chesterbrook, PA) is the first licensed drug for the treatment of Peyronie&[prime]s disease (PD). Although PD is strongly associated with erectile dysfunction, there are no studies of the effects of CCH on isolated human corpus cavernosum (HCC) smooth muscle function. A clinical study did not show any significant changes on penile duplex Doppler ultrasound after four cycles of CCH (0.58 mg). We aimed to evaluate the effects of different concentrations of CCH on nitric oxide (NO)-dependent and -independent nitrergic relaxations of HCC in organ bath studies, in order to understand if CCH can improve HCC relaxation, and, thus, ED in PD patients.
Methods: HCC samples were obtained from men undergoing penile prosthesis implantation (n = 10). After phenylephrine (Phe) contraction, electrical field stimulation (EFS) and acetylcholine (ACh)-induced relaxation of [0.23 and 0.9 mg] CCH incubations of HCC strips were performed using organ bath preparations. HCC measurements of endothelial NO synthase, neuronal, and vascular endothelial growth factor were evaluated through immunostaining and Western blotting. Type I and III collagen levels were evaluated by Western blot analysis
Results: Pre-incubation with various doses of CCH did not reduce the maximal contractile response of Phe and the relaxant response to EFS (20Hz) in HCC. Nevertheless pre-incubation with CCH significantly reduced contractile tension evoked by EFS (80 Hz) by 37.5%, and increased ACh-induced relaxation (10-3M) five-fold at 0.23 and 0.9 mg. CCH appeared to be safe and possibly reduced corporal fibrosis, as well as collagen type I and III expressions in the high-dose CCH treated HCC samples when compared with the untreated HCC samples.
Conclusions: The potential relaxant effect of CCH on HCC smooth muscle may enhance parasympathetic cholinergic response and inhibit sympathetic adrenergic receptors, resulting in reduced EFS-induced contraction (80Hz). The relaxation response to CCH is likely to be dependent of NO-cGMP pathway and structural changes in HCC collagen. Incubating HCC with 0.9 mg CCH may have in vitro pro-erectile effects on the penile vasculature. This adds to the safety profile of CCH. More studies are required to examine the therapeutic potential of CCH pro-erectile effects with increased dosing in vivo to better address PD and the associated erectile dysfunction.