Reasons and predictive factors for discontinuation of PDE-5 inhibitors despite successful intercourse in erectile dysfunction patients.

This study was aimed to identify characteristics of ED patients who discontinued PDE5i despite successful intercourse. Data were collected using a questionnaire from 34 urologic clinics regardless of the effect (success or failure) of PDE5i treatment by visiting the clinics (717), e-mail (64) or post (101) for 882 ED patients who had previously taken any kind of PDE5i on demand four or more times. Discontinuation of PDE5i was defined if the patient had never taken PDE5i for the previous 1 year despite successful intercourse. Of the 882 patients, 485 were included in the final analysis. Difference in the socio-demographic, ED- and partner-related data between the continuation and discontinuation group and factors influencing discontinuation of the PDE5i were analyzed. Among 485 respondents (mean age, 53.6), 116 (23.9%) had discontinued PDE5i use despite successful intercourse. Most common reasons for the discontinuation were 'reluctant medication-dependent intercourse' (31.0%), 'spontaneous recovery of erectile function without further treatment' (30.2%), and 'high cost' (26.7%). In multiple logistic regression analysis, independent factors influencing discontinuation of the drug were cause of ED (psychogenic), short duration of ED, low education (⩽ middle school), and religion (Catholic). In partner-related compliance, only partner's religion (Catholic) was a significant factor.

A double-blind, randomised- placebo, controlled, parallel group, multicentre, flexible-dose escalation study to assess the efficacy and safety of sildenafil administered as required to male outpatients with erectile dysfunction in Korea.

The efficacy and safety of sildenafil was evaluated in a randomiSed, double-blind, placebo-controlled, flexible-dose study in Korean men aged 28-78 y with erectile dysfunction (ED) of broad-spectrum aetiology and more than 6 months duration. A total of 133 patients were randomised at six centres in Korea to receive either sildenafil (50 mg initially, increased if necessary to l00 mg or decreased to 25 mg depending on efficacy and tolerance) (n=66) or matching placebo (n=67) taken on an 'as needed' basis l h prior to anticipated sexual activity for a period of 8 weeks. At the end of this time, the primary efficacy variables relating to the achievement and maintenance of erections sufficient for sexual intercourse, and the secondary efficacy variables, which included: (1) the five separate domains of sexual functioning of the International Index of Erectile Function (IIEF) scale, (2) the percentage of successful intercourse attempts, and (3) a global assessment of erections, were all statistically significantly improved by sildenafil in comparison with placebo (P&<0.0001). Treatment-related adverse events occurred in 56.1% of patients receiving sildenafil and 20.9% receiving placebo. The most common adverse events with sildenafil were vasodilatation (flushing), headache and abnormalities in colour vision (31.8, 22.7 and 6.1% of patients, respectively), and most were mild in nature. The efficacy and safety of sildenafil in this population of Korean men appears similar to that reported in other studies in western populations.

Synergistic effects of sildenafil on relaxation of rabbit and rat cavernosal smooth muscles when combined with various vasoactive agents.

OBJECTIVE: To evaluate which vasoactive agents have synergistic effects on the cavernosal smooth muscles of rabbits and rats when the agents are combined with sildenafil. MATERIALS AND METHODS: Relaxation responses of cavernosal smooth muscle to single agents (phentolamine, moxisylyte, sodium nitroprusside, forskolin, vasoactive intestinal peptide, VIP, papaverine and sildenafil) in the rabbit, and prostaglandin-E1 and sildenafil in the rat, and to combinations of each agent plus sildenafil, were assessed in vitro. The response to sildenafil of the rabbit strips with and without incubation with l-arginine (1 mmol/L) for 20 min was also evaluated. The effective concentrations for a half-maximal response of single agents and combination solutions were compared. RESULTS: All single agents induced concentration-dependent relaxation of the rabbit and rat cavernosal smooth muscles. There was significant synergism on rabbit cavernosal smooth muscle when the sildenafil was combined with forskolin, sodium nitroprusside, VIP or phentolamine. There was also significant synergism with sildenafil plus prostaglandin-E1 in rat cavernosal muscles. There were no synergistic effects of combinations of sildenafil plus moxisylyte, papaverine or l-arginine. CONCLUSIONS: These results suggest potentially effective combined therapies of sildenafil and intraurethral or intracavernosal prostaglandin-E1, intracavernosal forskolin or VIP, or oral phentolamine for patients with erectile dysfunction who have no success after monotherapy with these agents.

Comparison of peripheral inhibitory effects of clomipramine with selective serotonin re-uptake inhibitors on contraction of vas deferens: in vitro and in vivo studies.

PURPOSE: We compared the peripheral inhibitory effects of the tricyclic antidepressant clomipramine with those of various selective serotonin re-uptake inhibitors on the contractile response of the vas deferens. MATERIALS AND METHODS: The contractile responses of 17 circular smooth muscle strips of human vas deferens to 10-4 M. norepinephrine were observed in the absence and presence of clomipramine, and the selective serotonin re-uptake inhibitors fluoxetine, sertraline and paroxetine. The intraluminal pressure response of rat vas deferens to electrical stimulation of the hypogastric nerve was measured in 5 rats in the central plus peripheral effect group before and after the intravenous injection of 4.2 mg./kg. clomipramine or 8.3 mg./kg. sertraline. The pressure response to each agent was also observed after the transection of all proximal sympathetic input to the hypogastric nerve in 5 animals in the peripheral effect group. RESULTS: Clomipramine was about 100-fold more potent than sertraline, fluoxetine or paroxetine for inhibiting the norepinephrine induced contraction of human vasal muscle strips. The inhibitory effect of sertraline on rat intravasal pressure in the peripheral effect group was significantly lower than in the central plus peripheral effect group (p <0.05), while no significant difference was noted in the 2 groups regarding clomipramine. The effect of clomipramine was significantly higher than that of sertraline in the central plus peripheral and peripheral effect groups (p <0.01). CONCLUSIONS: Differences in potency of the peripheral inhibitory effects of the selective serotonin re-uptake inhibitors and clomipramine may contribute to their differential effects on delaying ejaculatory latency in patients with premature ejaculation.

Risk factors for an early increase in dose of vasoactive agents for intracavernous pharmacotherapy.

AIMS: This study was to identify factors that influence the early increase in the dose of intracavernous vasoactive agents to maintain erection for satisfactory intercourse and to elucidate when the dose increase would begin. METHODS: Seventy-nine patients using intracavernous pharmacotherapy with tri-mix (PGE(1), papaverine, and phentolamine) over a 3- to 4-year period were enrolled. At 3-month intervals, patients were questioned about changes in dose to maintain erection for satisfactory intercourse and frequency of injection, and underwent examination of the penis. The patients were divided into 2 groups: group A, dose increase of > or = 20% after initiating home therapy, and group B, no change or an increase in dose < 20%. RESULTS: A significant increase (p < 0.01) in dose was started 2-3 years after initiating pharmacotherapy. The initial doses of group A at 2-3 and 3-4 years were significantly higher than those of group B (p < 0.01). There were no significant differences in the age of the patients, duration of erectile dysfunction, incidence of accompanying vascular risk factors, frequency of injection, or incidence of fibrous plaques between group A and group B, both at 2-3 and 3-4 years. CONCLUSION: The initial dose of intracavernous vasoactive agents (tri-mix) may be a unique risk factor for the early increase in dose to maintain erection for satisfactory intercourse.

Multicenter study of the treatment of erectile dysfunction with transurethral alprostadil (MUSE) in Korea.

A Korean multicenter study was conducted to assess the effectiveness of transurethral alprostadil with MUSE in 334 subjects with chronic erectile dysfunction (ED) who were enrolled in 21 clinical centers. Patients with psychogenic impotence comprised about 30% of subjects. Intraurethral alprostadil was titrated in a stepwise fashion in the clinics from 250 to 500 or 1000 mcg based on erectile response and tolerability. The erectile responses were evaluated using an erection assessment scale (score of 1-5). The dose that produced a maximal penile response of score 5 (full rigid erection) or 4 (full tumescence, partial rigidity) was selected for home treatment. Patients who showed partial erection (score of 3) with 1000 mcg were also included in the home-treatment group. In-clinic phase: 198 men (59.3%) had maximal penile responses of score 4 or 5. The rate of maximal responses was not related to patient age, etiology or duration of the ED. A total of 228 (68.3%) men progressed to home treatment. The overall level of comfort of the transurethral alprostadil was rated as uncomfortable or very uncomfortable in 12%. Home phase: During the two-month period of home treatment, 178 (78.1%) men had successful sexual intercourse at least once, and 78.2% of administrations (1976) resulted in successful intercourse. The main causes of drop-out were insufficient erectile response in 27 men (11.8%), adverse reactions (mostly penile or urethral pain) in 7 (3.1%) or both in 7 (3.1%). In conclusion, transurethral alprostadil could be a suitable treatment option for patients with ED regardless of age and etiology of ED. Efficacy in an Asian population (Korea) is comparable to that reported previously in Caucasians.

The effects of isolated lipoproteins and triglyceride, combined oxidized low density lipoprotein (LDL) plus triglyceride, and combined oxidized LDL plus high density lipoprotein on the contractile and relaxation response of rabbit cavernous smooth muscle.

The aim of this study was to investigate the effects of isolated lipoproteins and triglyceride (TG), and the effects of combined oxidized low density lipoprotein (LDL) plus TG and the combined oxidized LDL plus high density lipoprotein (HDL) on the contractility and relaxation response of rabbit cavernous smooth muscle. Cavernous muscle strips from New Zealand White rabbits were studied in organ chambers for isometric tension measurement. The strips were exposed to HDL, LDL, oxidized LDL, TG, combined oxidized LDL plus TG and combined oxidized LDL plus HDL for 30 min. Both HDL and LDL did not affect contraction and relaxation responses of the cavernous muscles. The oxidized LDL did not affect norepinephrine (NE)-induced contractility of the strips, but significantly (p < 0.05) decreased the relaxation response to endothelium-dependent agonist, acetylcholine (Ach). Non-specific NO synthase inhibitor (L-NAME) completely inhibited the relaxation response to Ach, and L-arginine partially improved the diminished relaxation. TG did not significantly change the relaxation responses to Ach, but decreased the contractility of cavernous muscle to NE. Neither the combined oxidized LDL plus TG nor oxidized LDL plus HDL had significant synergistic or detoxication effects on the contractility and relaxation responses. In conclusion, oxidized LDL may have acute toxic effects on the endothelium-dependent, NO-mediated relaxation, but not on the contractility, of rabbit cavernous smooth muscle. TG may decrease contractility of the cavernous muscle. There may be neither synergistic nor detoxication effects on the contractility and relaxation response when TG or HDL is added to the oxidized LDL.

Inhibitory effect of serotonergic drugs on contractile response of the rat vas deferens to electrical nerve stimulation: in vivo study.

PURPOSE: To evaluate, in vivo, the inhibitory effects of certain serotonergic drugs on the contractile response of the rat seminal tract to electrical stimulation of the hypogastric nerve. MATERIALS AND METHODS: Twenty-five Sprague Dawley rats (250 to 300 gm. each) were equally divided into 5 groups based on experimental agent; normal saline, clomipramine, sertraline, paroxetine, and fluoxetine. The hypogastric nerve was electrically stimulated and the intraluminal pressure of the vas deferens was measured, both pretreatment and 30 minutes after intravenous injection of four different doses (0.1 to 20 x the therapeutic dose) of each agent. Variations of responses relative to the time after administration of each agent (at 10- and 20-fold concentration) were also observed. RESULTS: All serotonergic drugs caused dose-dependent inhibition of elevation in intraluminal pressure of the vas deferens (p <0.05). The inhibitory effect of clomipramine was significantly better (p <0. 05) than that of fluoxetine at a 1-fold dose, while no significant differences were noted among clomipramine, sertraline and paroxetine. At doses of 10- and 20-fold, clomipramine had the strongest inhibitory effect, followed by sertraline and paroxetine, then fluoxetine (p <0.05). No differences were found in the inhibitory effects of the drugs studied, as a function of the time after injection. CONCLUSIONS: Clomipramine was the most potent drug for inhibition of elevation in intraluminal pressure of the rat vas deferens induced by electrical stimulation of the rat hypogastric nerve. The stronger inhibitory effect of clomipramine than the selective serotonin reuptake blockers suggests a possible peripheral action of clomipramine in addition to its central serotonergic action.

Fracture at the input tube-cylinder junction of AMS 700 inflatable penile prostheses as a complication of a modified implantation technique in a series of 99 patients.

OBJECTIVES: To compare the incidence of a specific failure mode of the penile implant, fracture at the input tube-cylinder junction, with respect to two methods of managing the input tube. METHODS: AMS 700 series three-piece inflatable penile prostheses were implanted in the first 26 patients using an ordinary technique in which the input tubing runs alongside the cylinder within the corpus and exits through the corporotomy (method A). In the subsequent 73 men, the input tube exited through a separate stab wound in the proximal corpus using a modification of the basic surgical technique (method C). The mean follow-up period was 136.4 months for method A and 69.0 months for method C. The incidence of fracture at the junction of the input tube and cylinder was compared according to the variables of input tube management, prosthesis type, and width of the proximal corpora. RESULTS: The overall incidence of mechanical failure was 12.1%. Fractures at the input tube-cylinder junction with leaking occurred in 7 patients. The cylinders in these patients were all implanted using method C. The incidence of fracture at the junction was significantly higher (P <0.05) in men with narrow corpora (17.1%) than in the others (0%), regardless of the type of prosthesis implanted. The average functional duration of the failed prostheses was 66.1 months. CONCLUSIONS: The modified surgical procedure (method C) should be avoided in patients with a narrow-width penis because of an increased likelihood of damage to the input tube-cylinder junction.

Involvement of endothelial nitric oxide synthase in the impaired endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbit.

The present study was designed to evaluate whether functional impairment and/or protein expression of constitutive nitric oxide synthase (cNOS; endothelial NOS [eNOS] and neuronal NOS[nNOS]) was involved in impairment of endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbits. New Zealand White rabbits were randomly divided into control and experimental groups. The control group (n=20) received a regular diet, while the two experimental groups (n=20 for each) were fed a 2% cholesterol diet for 4 and 8 weeks, respectively. We conducted isometric tension studies with endothelium-dependent and endothelium-independent vasodilators with or without preincubation with L-arginine and nonadrenergic, noncholinergic (NANC)-selective electrical field stimulation on isolated strips of corpus cavernosum. Expression of cNOS (eNOS and nNOS) protein was assessed by Western blot analysis. cNOS activities in both cytosolic and particulate fractions were measured by determining the conversion of L-[U-14C] arginine to L-[U-14C] citrulline. Blood levels of cholesterol were significantly higher (P < 0.01) in the experimental groups than in the control group. The relaxation responses to endothelium-dependent agents (acetylcholine and adenosine 5'-diphosphate [ADP]) were significantly reduced (P < 0.05) in both experimental groups, regardless of their incubation with L-arginine, compared with the control group. However, no differences were found among the three groups in the relaxation response to endothelium-independent agents (papaverine and nitroprusside) and to NANC-selective electrical field stimulation. There was no difference in immunoreactive nNOS from cytosolic and particulate fractions between the cavernous tissues of the control and experimental groups. nNOS protein levels in the particulate fractions were markedly lower than in the cytosolic fractions. The particulate cNOS activity was significantly decreased (P < 0.05) in the experimental groups compared with the control group, while the cytosolic cNOS activity in the experimental groups was not different from that found in the control group. Therefore, it is concluded that functional impairment of eNOS, rather than of nNOS, may lead to impairment of cavernous smooth muscle relaxation in response to endothelium-mediated stimuli in hypercholesterolemic rabbits.

Comparison of relaxation responses of cavernous and trigonal smooth muscles from rabbits by alpha1-adrenoceptor antagonists; prazosin, terazosin, doxazosin, and tamsulosin.

Alpha1a-adrenergic receptor (AR) primarily mediates the contraction of the prostatic and cavernous smooth muscles. Among clinically available alpha1-AR antagonists for the medical management of benign prostatic hyperplasia (BPH), tamsulosin has a modest selectivity for alpha1A- and alpha1D- over alpha1B-ARs. To compare the effects of various alpha1-AR antagonists on relaxation responses of cavernous and trigonal smooth muscles, isometric tension studies with relatively selective (tamsulosin) and non-selective (prazosin, doxazosin, and terazosin) alpha1A-AR antagonists, were conducted in the cavernous and trigonal muscle strips of rabbits (n=10 each). Tamsulosin had the strongest inhibitory effect on contraction of trigonal smooth muscle among the various alpha1-AR antagonists, and the inhibitory activities of prazosin, doxazosin, and terazosin were not statistically different. All alpha1-AR antagonists caused concentration-dependent relaxation of the cavernous muscle strips. Tamsulosin was shown to have greater potency than prazosin (more than 100-fold), doxazosin (more than 1000-fold), and terazosin (more than 1000-fold), in relaxation of cavernous smooth muscle. In conclusion, tamsulosin might be the most effective drug among the four commonly used alpha1-AR antagonists for the medical management of BPH. Tamsulosin might be a potential substitute for phentolamine in combination with vasoactive agents as an intracavernous injection therapy for patients with erectile dysfunction.

Effects of bacterial endotoxin on the contraction and relaxation responses of the rabbit cavernous smooth muscles.

PURPOSE: We evaluated effects of bacterial endotoxin during septicemia on contraction and relaxation responses of cavernous smooth muscles in rabbits. MATERIALS AND METHODS: We performed isometric tension studies with norepinephrine (NE), endothelium-dependent and endothelium-independent vasodilators, and nonadrenergic noncholinergic (NANC)-selective electrical field stimulation on the muscle strips of control and endotoxin (lipopolysaccharide; LPS)-treated rabbits. To determine reversibility of the LPS effects on the cavernous smooth muscle, the contraction and relaxation studies were repeated after resting the strips for 1 day at 4C. We also investigated the effect of the nonspecific nitric oxide synthase (NOS) inhibitor (NW-nitro-L-arginine methyl ester; L-NAME) and the selective immunologic NOS inhibitor (aminoguanidine) on reactivity of the strips to NE and acetylcholine. RESULTS: Contractile response to NE was significantly (p <0.01) reduced in the cavernous smooth muscles from the systemically and locally LPS-treated rabbits, compared with control group. Both aminoguanidine and L-NAME markedly improved the diminished contraction of the strips. Relaxation response to endothelium-dependent agonists (acetylcholine and bradykinin) was significantly (p <0.05) decreased in the LPS-treated groups, compared with the control group but not to endothelium-independent vasodilators (papaverine and verapamil) and NANC-selective electrical field stimulation. L-NAME completely inhibited the relaxation response to acetylcholine in the control and LPS-treated groups but aminoguanidine did not. The impaired contraction and relaxation of the strips was completely restored after resting for 1 day. CONCLUSIONS: Bacterial endotoxin may cause non-endothelial overproduction of NO and inhibition of endothelium-derived NO production, which may contribute to impairment of contraction and relaxation of rabbit cavernous smooth muscles.

Comparison of the synergistic effects of tamsulosin versus phentolamine on penile erection: in vitro and in vivo studies.

In vitro and in vivo studies were performed to determine the potential use of tamsulosin (TAM) versus phentolamine (PHE) for intracavernosal injection (ICI) therapy when mixed with papaverine (PAP) and/or prostagladin E1 (PGE1) or with vasoactive intestinal polypeptide (VIP) for the treatment of erectile dysfunction. We performed isometric tension studies on rabbit (n = 15), dog (n = 5), and human (n = 10) cavernous smooth muscle strips with TAM, PAP, PHE, VIP, PGE1, and the combinations of PAP and PHE; PAP and TAM; VIP and PHE; VIP and TAM; PAP, PGE1 and PHE; and PAP, PGE1 and TAM. TAM-containing trimix (PAP 18.75 mg, PGE1 6.25 micromg, and TAM 0.875 mg per ml) or PHE-containing trimix (PAP, PGE1, and PHE 0.625 mg per ml) were also injected into the cavernous bodies of ten mongrel dogs. Among the single agents, TAM and PGE1 (only in human) had the strongest effect on the relaxation of cavernous muscles in rabbit, dog, and human strips (P<0.05). Relaxation responses to 2- or 3-drug mixtures containing tamsulosin were also significantly better (P<0.05) than PHE-containing ones in rabbit, dog, and human strips. The increase in intracavernosal pressure with a TAM-containing trimix was higher than with a PHE-containing one (0.03 ml; 81.2 vs. 75.8 mm Hg, 0.04 ml; 103.2 vs. 94.3 mm Hg), although not statistically different. The drop in systemic blood pressure was lower after injection of a TAM-containing trimix than a PHE-containing one, although not statistically different. In conclusion, tamsulosin might be a more efficacious and safer agent to use for ICI therapy than phentolamine.

Efficacy and safety of fluoxetine, sertraline and clomipramine in patients with premature ejaculation: a double-blind, placebo controlled study.

PURPOSE: We compared the efficacy and safety of fluoxetine, sertraline, clomipramine and placebo for the oral pharmacotherapy of premature ejaculation. MATERIALS AND METHODS: The study included 36 men (mean age 44 years) who had intravaginal ejaculation latency of less than 2 minutes. Patients took each of 3 drugs and the placebo consecutively during a 4-week period per each agent. Efficacy and side effects data were obtained by a self-reported patient questionnaire that rated intravaginal ejaculation latency, sexual satisfaction of patient and partner, and possible side effects. RESULTS: After 4 weeks of treatment with placebo, fluoxetine, sertraline and clomipramine the mean intravaginal ejaculation latency time was significantly increased from 46 seconds to 2.27 minutes, 2.30 minutes, 4.27 minutes and 5.75 minutes, respectively (all p <0.01). However, treatment with clomipramine or sertraline caused a greater increase in mean intravaginal ejaculation latency time than fluoxetine or placebo (p <0.01). Patient sexual satisfaction rate after treatment with clomipramine was significantly higher (p <0.05) than with sertraline, fluoxetine or placebo. Partner sexual satisfaction rate was also higher with clomipramine than with sertraline or fluoxetine but no statistical difference was found. The incidence of side effects with clomipramine was significantly higher (p <0.05) compared to that of fluoxetine, sertraline and placebo, while no significant difference among sertraline, fluoxetine and placebo was noted. CONCLUSIONS: In men with premature ejaculation clomipramine was the most useful drug in terms of efficacy. Treatment with sertraline was nearly as effective and had a lower incidence of side effects.

Changes in erectile response to repeated audiovisual sexual stimulation.

OBJECTIVES: To determine changes in erectile response to repeated audiovisual sexual stimulation in patients with psychogenic impotence and normal men. METHODS: The same erotic video was shown to 45 men (20 patients with psychogenic impotence and 25 normal men) for 3 consecutive days. Their erectile responses during the audiovisual stimulation were monitored using RigiScan (Dacomed, Minneapolis, Minn., USA), and the maximal rigidity of erection, sustained for more than 5 min, was measured. The rigidities on the first, second and third days were comparatively analyzed. Whether previous multiple viewings of the erotic movie and previous exposure to the same or a similar movie influenced the erectile response were also evaluated. RESULTS: Rigidity on the third day was significantly decreased compared to that on the first day in both patients with psychogenic impotence and normal controls (p < 0.05), regardless of the frequency of previous viewings and the previous exposure to a similar movie. Rigidity on the first day was significantly lower in the group with multiple viewings than in the group with fewer viewings (p < 0.05). CONCLUSIONS: Real-time monitoring of penile erection during audiovisual sexual stimulation may result in false-negative responses when patients are repeatedly exposed to the stimulation.

Characteristics of pain following intracavernous injection of prostaglandin E1.

The aim of this study was to determine the incidence and characteristics of pain following intracavernous injection of prostaglandin E1 (PGE). We injected PGE into the cavernous tissues of 156 patients with erectile dysfunction who had never previously been injected with PGE. The incidence and characteristics of pain after injection were evaluated by the patients' response to a questionnaire. The intensity of pain was determined by the degree of impediment to intercourse, verbal rating scale (VRS), numerical rating scale (NRS), and visual analogue scale (VAS). Patients scoring 'no pain' on the VRS, NRS, and VAS were 11.5%, 7.7%, and 7.7%, respectively. Overall incidence of pain was 91%. There was 'much' or 'very much' impediment to intercourse because of pain in 14 (9.1%) patients. The most common kind of pain was 'heavy pain' in 90% of the patients followed by 'throbbing' in 38%, 'aching' in 21%, 'tightening' in 18%, and 'shooting' in 13%. The mean duration of pain was 101.2 +/- 63.7 minutes and it lasted during the entire erection period in 71(50.4%) patients. There were significant correlations among the degree of impediment to intercourse, VRS, NRS, and VAS scores (all p < 0.01). However, no association was noted between pain intensity and both erectile response to PGE and injected dose. The higher incidence of intracavernous PGE-induced pain reported here compared to other studies might be related to difference in pain thresholds among races. The high incidence of pain but low frequency of much impediment to intercourse would be related to the pain characteristics as well as the intensity of pain.

Involvement of superoxide radical in the impaired endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbits.

Involvement of the superoxide radical in impaired relaxation of penile cavernous smooth muscle in hypercholesterolemia was investigated. New Zealand White rabbits (n = 40) were randomly divided into control and treatment groups. The control group (n = 20) received a regular diet while the treatment group (n = 20) was fed a diet of 2% cholesterol for 8 weeks. Blood level of cholesterol in the cholesterol-fed group was significantly higher than that of the control group. The contraction responses of cavernous tissues to norepinephrine were not significantly different in the two groups. The relaxation responses to endothelium-dependent agents (acetylcholine, bradykinin) were significantly reduced in the hypercholesterolemic group compared with the control group. However, the relaxation responses to endothelium-independent agents (papaverine, verapamil) were not significantly different in the two groups. The production of superoxide radicals was significantly higher in the hypercholesterolemic group than in the control group (P < 0.01). The activity of superoxide dismutase (total SOD, Mn-SOD, Cu,Zn-SOD) increased significantly in the hypercholesterolemic group compared with the control group (P < 0.05). The activities of catalase and glutathione peroxidase also increased in the hypercholesterolemic group, but were not significantly higher than those of the control group. Therefore, production of the superoxide radicals in rabbit cavernous tissues increases in the state of hypercholesterolemia, which may lead to functional impairment of cavernous smooth muscle relaxation in response to endothelium-mediated stimuli.

Corporeal blood gas changes according to duration of drug-induced prolonged erection.

The corporeal blood gas changes in accordance with the duration of the prolonged erection which developed after intracorporeal pharmacotherapy with papaverine and phentolamine were investigated in 62 impotence patients. The picture of the corporeal blood taken from 15 psychogenic impotence patients (a control group) at 10 minutes after intracavernous injection when they showed full erections was arterial but there was pCO2 rise and pH drop compared to femoral artery blood taken simultaneously. As the erection lasted longer, significant gas changes of the cavernous blood began to appear (p < 0.0001): increase in pCO2 and decrease in pO2 from 4 hours, decrease in pH from 5 hours, decrease in O2 saturation from 6 hours. Erections lasting for more than 16 hours showed significantly worse hypoxia (p < 0.05). Therefore, to prevent hypoxia and metabolic acidosis, drug-induced prolonged erection would be better decompressed before it lasts for more than 4 hours.