PURPOSE:Digoxin use has long been recognized to affect adversely male sexual function but the underlying mechanism is poorly understood. Digoxin is a known inhibitor of sodium/potassium adenosine triphosphatase (sodium pump), a plasma membrane enzyme that has a role in the regulation of smooth muscle tone. We investigated the effects of digoxin on human corpus cavernosum smooth muscle contractility and overall erectile function.MATERIALS AND METHODS:In human corporeal smooth muscle strips the in vitro effects of digoxin were assessed on sodium pump activity as measured by digoxin inhibitable uptake of 86rubidium, basal tone and endothelium dependent, neurogenic and nitric oxide donor induced relaxation. An in vivo prospective double-blind, placebo controlled, crossover, 4-period investigation was performed in 6 healthy male volunteers. The effects of digoxin on serum hormones, erectile function questionnaire, visual sexual stimulation and nocturnal penile tumescence were recorded.RESULTS:In vitro digoxin caused concentration dependent inhibition of 86rubidium uptake (half maximum effect at 0.01 microM.) and contraction of corporeal smooth muscle (half maximum effect at 0.8 microM.). Therapeutic concentrations of digoxin (2 nM.) also inhibited relaxation induced by acetylcholine and electrical field stimulation, which release nitric oxide from corpus cavernosum endothelial cells and nonadrenergic noncholinergic nerves, respectively. In vivo digoxin diminished penile rigidity during visual sexual stimulation and nocturnal penile tumescence testing compared to placebo without influencing libido or serum testosterone, estrogen or luteinizing hormone levels.CONCLUSIONS:Digoxin associated alteration of human erectile function may be explained, in part, by inhibition of corporeal smooth muscle sodium pump activity, which promotes contraction and impedes nitric oxide induced relaxation. Such findings suggest therapeutic use of digoxin for treatment of recurrent priapism states.

Transforming growth factor-beta(1) (TGF-beta(1)) induces fibrillar collagen synthesis in human corpus cavernosum smooth muscle cells (HCC SMC). TGF-beta(1) also induces TGF-beta(1) mRNA expression as well as TGF-beta receptors on HCC SMC, Prostaglandin E-1 (PGE(1)) suppresses TGF-beta(1) effects on HCC SMC, The aim of this study was to determine if HCC SMC synthesize PGE and if TGF-beta(1) expression and PGE synthesis are modulated by the oxygen tension. Both PGE and TGF-beta(1) were synthesized by HCC SMC in vitro. Reduced oxygen tensions consistent with in vivo penile flaccidity (30 mm Hg PO2) inhibited PGE synthesis by 68% and induced TGF-beta(1) mRNA by two to three fold. Examination of corporal tissue biopsies by immunohistochemistry staining revealed TGF-beta(1) limited to myocytes, with intense cytoplasmic immunoreactivity, These results are consistent with a PGE:TGF-beta(1) paradigm; that is, PGE and TGF-beta(1) modulate each other to regulate collagen synthesis in human corpus cavernosum smooth muscle, Synthesis of PGE is favored at increased oxygen tension, conditions that suppress TGF-beta(1) production and collagen synthesis, whereas reduced oxygen tension inhibits prostanoid production and favors TGF-beta(1) and collagen synthesis. Because functional erectile tissue depends on the smooth muscle/connective tissue ratio, the advent of therapeutic PGE(1) would suggest a potential prophylactic means of maintaining a functional collagen/smooth muscle balance.

Purpose: We investigated forskolin, a direct adenylate cyclase activator, as an intracavernosal vasoactive agent in management of vasculogenic impotence.Materials and Methods: Concentration responses for forskolin and prostaglandin El induced relaxation of phenylephrine precontracted strips of human corpus cavernosum smooth muscle were constructed in vitro. Cyclic adenosine monophosphate (cAMP) synthesis was determined with papaverine, phentolamine, prostaglandin El and forskolin in human corpus cavernosum smooth muscle cell cultures. Dose-dependent hemodynamic responses to intracavernosal forskolin (5 to 20 mu g.)were evaluated in a New Zealand White rabbit model. Safety and efficacy outcome data were obtained in vasculogenically impotent patients who signed informed consent and met strict inclusion and exclusion criteria that included having had standard self-injection therapies fail.Results: In vitro forskolin and prostaglandin El alone caused concentration dependent relaxation with an EC50 of approximately 200 nm, and 16 nm,, respectively, When the 2 agents were combined, the concentration response curve for relaxation shifted to the left. cAMP production was highest in cells treated with prostaglandin El and forskolin and was unaffected by papaverine or phentolamine. In 3 animals, equilibrium intracavernosal pressure and duration of erection had a dose dependent increase. Clinical investigation in 31 patients showed no adverse events with a mean of 14 +/- 4, range 11 to 18 months of followup. Overall 61% reported improvement in rigidity and/or erection duration using intracavernosal forskolin (98 mu g./ml.), papaverine (29 mg,/ml,), phentolamine (0.98 mg./ml,) and prostaglandin EB (9.8 mu g./ml.).Conclusions: Forskolin is a United States Food and Drug Administration nonapproved vasoactive agent that acts in synergism with prostaglandin El to induce smooth muscle relaxation. In combination with other vasoactive agents, forskolin has demonstrated preliminary safety and efficacy in patients with vasculogenic impotence resistant to standard 3-agent pharmacotherapy.

New video imaging technologies have significantly improved the development of minimally invasive surgical and laparoscopic procedures. The next step in this evolution, the advent of more complex procedures performed under minimally invasive conditions, demands a greater need for accurate depth perception; further improvements in imaging technology as well as instrumentation are needed for the surgeon to perform difficult manipulative tasks with the same skill, accuracy, and speed as in open surgery. Two different techniques are currently available to produce 3-dimensional image: the 'with glasses' technique and the 'glasses-free' technique. The purpose of this experiment is twofold. First, to objectively compare the 3-D images created by the 'glasses-free' monitor, the passive glasses 3-D system, and a 2-D monitor. The second objective was to subjectively assess the quality of each screen as perceived by the operator.

three-dimensional screen, and a two-dimensional imaging system. An objective analysis consisting of two experiments was conducted. The first experiment was designed to assess depth perception. Both 3-D imaging systems were compared to each other and a 2-D imaging system. A statistically significant difference existed between the 2-D screen and both of the 3-D screens (p < 0.001). There was no statistical difference found between the ''glasses-free'' 3-D screen and the passive glasses 3-D screen in either experiment. The second experiment was task oriented designed to compare the new, ''glasses-free'' 3-D imaging screen with the passive glasses 3-D screen. In this inanimate setting, the task of passing a needle and suture through a series of hoops was performed faster with the passive glasses 3-D screen but this difference was not statistically significant.Conclusion: The 3-D screens clearly produced more accurate assessment of depth than the 2-D screen. The new, ''glasses-free'' 3-D screen produced comparable results to the established passive glasses 3-D screen.