ABSTRACT
INTRODUCTION: Receptors for natriuretic peptides have been demonstrated as potential targets for the treatment of male erectile dysfunction. AIM: This study investigates the relaxant effects of the atrial natriuretic peptide (ANP) and uroguanylin (UGN), and expression of natriuretic peptide receptors on strips of human corpora cavernosa (HCC). MAIN OUTCOME MEASURES: Quantitative analysis of natriuretic receptor expression and relaxation of precontracted strips were used to assess the membrane-bound guanylate cyclase-cyclic guanosine monophosphate (cGMP) pathway in HCC strips. METHODS: HCC was obtained from a cadaver donor at the time of collection of organs for transplantation (14-47 years) and strips were mounted in organ baths for isometric studies. RESULTS: ANP and UGN both induced concentration-dependent relaxation on HCC strips with a maximal response attained at 300 nM, corresponding to 45.4±4.0% and 49±4.8%, respectively. The relaxation is not affected by 30 µM 1H-[1,2,4]oxaolodiazolo[4,3-a]quinoxalin-1-one (ODQ) (a soluble guanylate cyclase inhibitor), but it is significantly blocked by 10 µM isatin, a nonspecific particulate guanylate cyclase (pGC) inhibitor. UGN was unable to potentiate electrical field stimulation (EFS) or acetylcholine-induced relaxations. The potential role of pGC activation and cGMP generation in this effect is reinforced by the potentiation of this effect by phosphodiesterase-5 inhibitor vardenafil (55.0±7.5-UGN vs. 98.6±1.4%-UGN+vardenafil; P<0.05). The relaxant effect was also partially (37.6%) blocked by the combination iberitoxin-apamin but was insensitive to glybenclamide. The expression of guanylate cyclase receptors (GC-A, GC-B, GC-C) and the expression of the natriuretic peptide "clearance" receptor (NPR-C) were confirmed by real-time polymerase chain reaction. The exposure of HCC strips to ANP (1 µM) and UGN (10 µM) significantly increased cGMP, but not cyclic adenosine monophosphate (cAMP) levels. CONCLUSIONS: UGN relaxes HCC strips by a guanylate cyclase and K(ca)-channel-dependent mechanism. These findings obtained in HCC reveal that the natriuretic peptide receptors are potential targets for the development of new drugs for the treatment of erectile dysfunction.
Subject(s)
Atrial Natriuretic Factor/metabolism , Erectile Dysfunction/drug therapy , Natriuretic Peptides/pharmacology , Penis/surgery , Adolescent , Adult , Atrial Natriuretic Factor/drug effects , Cadaver , Cyclic AMP/metabolism , Cyclic GMP/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 5/metabolism , Erectile Dysfunction/enzymology , Erectile Dysfunction/metabolism , Guanylate Cyclase/metabolism , Humans , Male , Middle Aged , Muscle Relaxation/drug effects , Muscle Relaxation/physiology , Muscle, Smooth/drug effects , Muscle, Smooth/physiology , Natriuretic Peptides/metabolism , Penis/drug effects , Receptors, Atrial Natriuretic Factor , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Peptide/drug effects , Receptors, Peptide/metabolism , Soluble Guanylyl Cyclase , Young AdultABSTRACT
INTRODUCTION: We evaluated the feasibility and describe the surgical technique of using the Ti-Knot device TK-5 to secure the dorsal vein complex (DVC) during 20 consecutive cases of laparoscopic radical prostatectomy and cystoprostatectomy. TECHNICAL CONSIDERATIONS: Bloodless DVC ligation and transection was successfully achieved in 19 (95.03%) of 20 cases. In only 1 case, venous bleeding occurred after DVC transection. However, in this case, the two stitches used to ligate the DVC were tightly tied, and the bleeding probably occurred because the stitches were passed too superficially on the DVC. In another case, a third stitch had to be placed and tied with the aid of the Ti-Knot device because the second 2-0 Vicryl stitch placed at the DVC broke. In only 1 case did we experience some degree of trouble with the knotting process because one of the ends of the Vicryl suture slipped back into the abdominal cavity. The time to tie each suture with the Ti-Knot device, defined after the moment the needle was passed underneath the DVC to the moment the titanium knot was crimped and the Vicryl suture trimmed, was less than 1 minute (median 50 seconds, range 45 to 56) in all cases, except the case described above. No cases of the Ti-Knot device misfiring or malfunction occurred in this series. CONCLUSIONS: In our experience, the Ti-Knot titanium knot placement device proved to be safe and efficient during laparoscopic ligation and control of the DVC.
Subject(s)
Cystectomy , Laparoscopy , Prostate/blood supply , Prostate/surgery , Prostatectomy , Suture Techniques/instrumentation , Titanium , Cystectomy/methods , Equipment Design , Feasibility Studies , Humans , Ligation , Male , Prostatectomy/methods , VeinsABSTRACT
Increasing evidence in published reports has suggested that titanium staples may be well tolerated inside the urinary tract. Recently, the Italian Group from Piedmont described an "easy, fast, and reliable" technique of a Y-shaped ileal neobladder that was created during open surgery with nonabsorbable mechanical staples. They observed an acceptable 6% rate of stone formation at a median follow-up of 20 months (range 8 to 47). We describe our initial experience with laparoscopic Y-shaped orthotopic ileal neobladder constructed entirely intracorporeally using titanium staples exclusively in an attempt to mitigate the time-consuming and skill-intensive task of freehand suturing required during laparoscopic creation of continent reservoirs.
