TSPO ligand FGIN-1-27 controls priapism in sickle cell mice via endogenous testosterone production.

Priapism, a prolonged penile erection in the absence of sexual arousal, is common among patients with sickle cell disease (SCD). Hypogonadism is also common in patients with SCD. While the administration of exogenous testosterone reverses hypogonadism, it is contraceptive. We hypothesized that the stimulation of endogenous testosterone production decreases priapism by normalizing molecular signaling involved in penile erection without decreasing intratesticular testosterone production, which would affect fertility. Treatment of SCD mice with FGIN-1-27, a ligand for translocator protein (TSPO) that mobilizes cholesterol to the inner mitochondrial membrane, resulted in eugonadal levels of serum testosterone without decreasing intratesticular testosterone production. Normalized testosterone levels, in turn, decreased priapism. At the molecular level, TSPO restored phosphodiesterase 5 activity and decreased NADPH oxidase-mediated oxidative stress in the penis, which are major molecular signaling molecules involved in penile erection and are dysregulated in SCD. These results indicate that pharmacologic activation of TSPO could be a novel, targetable pathway for treating hypogonadal men, particularly patients with SCD, without adverse effects on fertility.

Functional Consequences of Mannose and Asialoglycoprotein Receptor Ablation.

The mannose receptor (ManR, Mrc1) and asialoglycoprotein receptor (ASGR, Asgr1 and Asgr2) are highly abundant endocytic receptors expressed by sinusoidal endothelial cells and parenchymal cells in the liver, respectively. We genetically manipulated either receptor individually or in combination, revealing phenotypic changes in female and male mice associated with changes in circulating levels of many glycoproteins. Both receptors rise and fall in response to progesterone during pregnancy. Thirty percent of Asgr2(-/-) and 65% of Mrc1(-/-)Asgr2(-/-) mice are unable to initiate parturition at the end of pregnancy, whereas Mrc1(-/-) mice initiate normally. Twenty five percent of Mrc1(-/-)Asgr2(-/-) male mice develop priapism when mating due to thrombosis of the penile vein, but neither Mrc1(-/-) nor Asgr2(-/-) mice do so. The half-life for luteinizing hormone (LH) clearance increases in Mrc1(-/-) and Mrc1(-/-)Asgr2(-/-) mice but not in Asgr2(-/-) mice; however, LH and testosterone are elevated in all three knockouts. The ManR clears LH thus regulating testosterone production, whereas the ASGR appears to mediate clearance of an unidentified glycoprotein that increases LH levels. More than 40 circulating glycoproteins are elevated >3.0-fold in pregnant Mrc1(-/-)Asgr2(-/-) mice. Pregnancy-specific glycoprotein 23, undetectable in WT mice (<50 ng/ml plasma), reaches levels of 1-10 mg/ml in the plasma of Mrc1(-/-)Asgr2(-/-) and Asgr2(-/-) mice, indicating it is cleared by the ASGR. Elevation of multiple coagulation factors in Mrc1(-/-)Asgr2(-/-) mice may account for priapism seen in males. These male and female phenotypic changes underscore the key roles of the ManR and ASGR in controlling circulating levels of numerous glycoproteins critical for regulating reproductive hormones and blood coagulation.

Safety and efficacy of blood exchange transfusion for priapism complicating sickle cell disease.

BACKGROUND: Priapism is unwanted painful penile erection that affects about 36% of boys and men with sickle cell disease (SCD) most of whom have sickle cell anemia. Clinically, priapism could be stuttering, minor, or major. The first two types are mild, last < 4 h, are usually treated at home, have good prognosis with normal sexual function. The major type of priapism lasts >4 h, associated with severe pain, requires hospitalization; often does not respond to medical treatment and may require shunt surgery. Untreated major priapism and surgical intervention often cause impotence. In this study, we report our 15-year experience in treating adult patients with SCD and major priapism with blood exchange transfusion after being refractory to other medical therapies. METHODS: Adult male African Americans patients with SCD and major priapism were enrolled in this study and followed for 15 years. A Haemonitics V-50 machine was initially used for whole blood exchange and was later replaced with Cobe Spectra machine for RBC exchange. RESULTS: We used 239 blood exchanges requiring 1,136 RBC units. We maintained a post-exchange hemoglobin level of about 10 g/dL and hemoglobin S level < 30%. None of the patients had any neurological complications such as headache, seizures, neurological deficits, or obtundation post-exchange. CONCLUSION: Together, the data indicate that blood exchange transfusion for the treatment of patients with SCD and major priapism is efficacious and safe.

Duration of priapism is associated with increased corporal oxidative stress and antioxidant enzymes in a rat model.

Ischaemic priapism is characterised by hypoxia, hypercapnia and acidosis with resultant corporal fibrosis. Studies reported decreased erectile recovery after treatment of priapism longer than 36 h. However, a recent study revealed that half of patients with 3 days of priapism achieved recovery after T-shunt, although mechanism remains unclear. We aimed to investigate the effect of priapism duration on oxidative stress and antioxidant enzymes. Twenty-four male rats were divided into four groups. Group 1 served as control. Groups 2, 3 and 4 represented 1, 2 and 4 h, respectively, of priapism induced by vacuum device and rubber band placed at base of erect penis. After 30 min of reperfusion, penectomy and blood withdrawal were performed to investigate levels of malondialdehyde (MDA), protein carbonyl (PC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx). Corporal MDA progressively increased with priapism duration (P = 0.01). Corporal SOD significantly differed between groups 1, 2 and 4. Also, there were significant differences in corporal GPx in groups 1 and 4 (P = 0.004) and groups 2 and 4 (P = 0.01). Corporal CAT was higher in group 4, but multivariable analysis revealed insignificant differences. Plasma MDA of the experimental groups was significantly higher than that of controls. There were no differences among groups in terms of other parameters. Increased antioxidant enzymes according to duration of priapism suggest that immediate treatment to relieve oxidative stress should be initiated in prolonged cases. However, further studies should be conducted to determine resistance mechanisms of the corpora to prolonged ischaemia.

Does platelet activity play a role in the pathogenesis of idiopathic ischemic priapism?

PURPOSE: Mean platelet volume (MPV) is used to measure platelet size and is defined as a potential marker of platelet reactivity. Higher MPV levels have been defined as a risk factor for increased incidence of intravascular thrombosis and its associated diseases. We aimed to determine whether a relationship exists between the MPV and veno-occlusive component of idiopathic ischemic priapism (IIP). MATERIALS AND METHODS: Between 2010 and 2014, 38 subjects were analyzed in two groups. One was composed of 15 patients with diagnosis as IIP in our institute, and the other contained 23 healthy control subjects. Complete blood count reports were retrospectively evaluated in both groups. MPV, platelet count (PLT), platelet distribution width (PDW), white blood cells (WBC), red blood cells (RBC), hemoglobin (Hb), reticulocyte distribution width (RDW) were measured in both groups. RESULTS: The mean ages were similar in IIP patients (45.86±15.82) and control subjects (47.65±10.99). The mean MPV values of IIP patients were significantly higher than control subjects (p<0.05). In contrast, also PLT counts were significantly lower in IIP patients, compared to control subjects (p<0.05). The mean hemoglobin and WBC values were significantly lower in control group (p<0.05). There was no significant difference of RBC, PDW and RDW values in both groups. CONCLUSIONS: We found that the MPV was significantly higher in IIP patients compared to control subjects. The high MPV levels may have contributed to the veno-occlusive etiopathogenesis of IIP disease. We strongly suggest further prospective studies to recommend the use of MPV in routine practice.

Priapism in homozygous sickle cell patients: important clinical and laboratory associations.

OBJECTIVE: To evaluate the relationship between the occurrence of priapism and important steady-state clinical and laboratory parameters in homozygous sickle cell disease (SCD). SUBJECTS AND METHODS: Steady-state clinical and laboratory data were obtained from the medical records of 126 male patients seen in the clinic over a 7-year period. Estimated prevalence rates, correlation coefficients and independent t tests were calculated to assess the relationship between priapism and several important clinical and laboratory indices. Patient data on age, haemoglobin concentrations, the frequency of crises per annum, leucocyte counts, platelet counts, serum bilirubin and aspartate transaminase were evaluated. RESULTS: The prevalence of priapism was determined to be 21.4%, and 22.2% of those affected had erectile dysfunction. There was a significant positive correlation between priapism and older age (p = 0.049) and lower leucocyte counts (p = 0.008). There was no significant relationship with other clinical or laboratory indices. CONCLUSION: About 1 in 4 of all homozygous older SCD patients had priapism, and an approximately similar ratio developed erectile dysfunction; they also had lower steady-state leucocyte counts. Other clinical and laboratory indicators of disease severity in SCD did not positively correlate with the occurrence of priapism, and this may imply an alternative pathogenetic mechanism.

How I manage priapism due to sickle cell disease.

Priapism due to sickle cell disease is a common but less well characterized complication of the disorder. It represents a "medical emergency" with the key determinant of outcome being the duration of penile ischaemia and time to detumescence of <4 h associated with a successful treatment outcome. Management can be outpatient-based and consists of pre-emptive strategies for early stuttering attacks based on prior health education of the association between the 2 disorders, non pharmacological management, outpatient penile aspiration and irrigation with or without instillation of alpha and beta adrenergic agonists for acute episodes and secondary prophylaxis to prevent the high rates of recurrences. The evidence to recommend medical prophylaxis is sparse but based on a consensus of experts and small phase 2 or III clinical trials. A clearer understanding of the molecular mechanism(s) involving normal and dysregulated erectile physiology, scavenger haemolysis and nitric oxide pathway paves way for the use of phosphodiesterase type 5 inhibitors in medical prophylaxis of stuttering attacks. These agents will need to be studied in multi-centre randomized phase III trials before they become standard of care. A multidisciplinary team approach is required to enhance "sexual wellness" and prevent erectile dysfunction in this sexually vulnerable group.

Priapism in sickle-cell disease: a hematologist's perspective.

INTRODUCTION: Priapism is a familiar problem to hematologists, well known for its association with sickle-cell disease (SCD). It also occurs in a variety of other hematological illnesses, nearly all forms of congenital hemolytic anemia, including other hemoglobinopathies and red blood cell membranopathies and enzymopathies. AIM: Provide urologists with a comprehensive review of priapism in SCD, with an emphasis on the perspective of a practicing hematologist. METHODS: Medline searches through July 2010 were conducted using the terms priapism, erectile dysfunction, and sickle cell. MAIN OUTCOME MEASURES: Expert opinion was based on review of the medical literature related to this subject matter. RESULTS: In men with SCD, large epidemiological studies have linked the risk of priapism to clinical markers of the severity of intravascular hemolysis. Extracellular hemoglobin and arginase released during hemolysis has been implicated in reducing nitric oxide bioavailability, although the relevance of hemolysis to vascular dysfunction has been challenged by some scientists. Consistent with the role of impairment of the nitric oxide axis, mice genetically deficient in nitric oxide production have also been shown to develop priapic activity. Provocative new data indicate that hemolysis-linked dysregulation of adenosine signaling in the penis contributes to priapism in sickle cell mice. Serious questions have arisen regarding the efficacy of mainstays of textbook dogma for treatment of acute severe priapism, including intravenous fluids, alkalinization, and exchange transfusion, and there is increasing acceptance for early aspiration and irrigation of the corpus cavernosum. CONCLUSION: For patients with sickle cell with recurrent priapism, there is very limited evidence for a medical prophylaxis role for hydroxyurea, etilefrine, pseudoephedrine, leuprolide, sildenafil, and other agents. Recent publications have highlighted nitric oxide and adenosine signal transduction pathways as worthy of additional research. Research and clinical management of sickle-cell priapism is strengthened by multidisciplinary collaboration between hematologists and urologists.

Priapism in sickle cell disease: Associations between NOS3 and EDN1 genetic polymorphisms and laboratory biomarkers.

Priapism is a urologic emergency characterized by an uncontrolled, persistent and painful erection in the absence of sexual stimulation, which can lead to penile fibrosis and impotence. It is highly frequent in sickle cell disease (SCD) associated with hemolytic episodes. Our aim was to investigate molecules that may participate in the regulation of vascular tone. Eighty eight individuals with SCD were included, of whom thirty-seven reported a history of priapism. Priapism was found to be associated with alterations in laboratory biomarkers, as well as lower levels of HbF. Patients with sickle cell anemia using hydroxyurea and those who received blood products seemed to be less affected by priapism. Multivariate analysis suggested that low HbF and NOm were independently associated with priapism. The frequency of polymorphisms in genes NOS3 and EDN1 was not statistically significant between the studied groups, and the presence of the variant allele was not associated with alterations in NOm and ET-1 levels in patients with SCD. The presence of the variant allele in the polymorphisms investigated did not reveal any influence on the occurrence priapism. Future studies involving larger samples, as well as investigations including patients in priapism crisis, could contribute to an enhanced understanding of the development of priapism in SCD.

Plasma asymmetric dimethylarginine concentrations in sickle cell disease are related to the hemolytic phenotype.

Asymmetric dimethylarginine (ADMA) is associated with pulmonary hypertension (PHT) in sickle cell disease (SCD). We studied the relationship of ADMA to other SCD-related complications. Plasma ADMA and associated parameters were determined in 52 HbSS/HbSbeta(0)-thalassemia and 24 HbSC/HbSbeta(+)-thalassemia patients. As expected ADMA levels were higher in HbSS/HbSbeta(0)-thalassemia patients with PHT (p=0.018), but also in those with other hemolysis-associated complications such as leg ulcers (p=0.012), cholelithiasis (p=0.008) and priapism (p=0.02) compared with counterparts without these complications. ADMA levels did not differ between patients with and without other disease related complications such as retinopathy and avascular osteonecrosis. Higher ADMA concentrations therefore seem to be associated to the hemolytic phenotype of SCD.

Ischemic priapism as a model of exhausted metabolism.

In vivo metabolic studies typically concern complex open systems. However, a closed system allows better assessment of the metabolic limits. Ischemic priapism (IP) constitutes a special model of the compartment syndrome that allows direct sampling from a relatively large blood compartment formed by the corpora cavernosa (CC). The purpose of our study was to measure metabolic changes and the accumulation of end products within the CC during IP. Blood gas and biochemical analyses of aspirates of the CC were analyzed over an 8-year period. Mean ± SD pH, pCO2 , pO2 , O2 -saturation, lactate, and glucose of the aspirated blood were determined with a point-of-care analyzer. Forty-seven initial samples from 21 patients had a pH of 6.91 ± 0.16, pCO2 of 15.3 ± 4.4 kPa, pO2 of 2.4 ± 2.0 kPa, and an O2 -saturation of 19 ± 24% indicating severe hypoxia with severe combined respiratory and metabolic acidosis. Glucose and lactate levels were 1.1 ± 1.5 and 14.6 ± 4.8 mmol/L, respectively. pH and pCO2 were inversely correlated (R2  = 0.86; P < 0.001), glucose and O2 -saturation were positively correlated (R2  = 0.83; P < 0.001), and glucose and lactate were inversely correlated (R2  = 0.72; P < 0.001). The positive correlation of CO2 and lactate (R2  = 0.69; P < 0.001) was similar to that observed in vitro, when blood was titrated with lactic acid. The observed combined acidosis underscores that IP behaves as a closed system where severe hypoxia and glycopenia coexist, indicating that virtually all energy reserves have been consumed.

Low nitric oxide level is implicated in sickle cell disease and its complications in Ghana.

BACKGROUND: Nitric oxide (NO) plays a fundamental role in maintaining normal vasomotor tone. Recent clinical and experimental data suggest that NO may play a role in the pathogenesis and therapy of sickle cell disease (SCD). The aim of this study was to determine NO metabolites (NOx) in SCD patients at steady state and in vaso-occlusive crisis (VOC), as well as those with hemolytic clinical sub-phenotype that includes leg ulcers and priapism. METHODOLOGY: This was a case-control cross-sectional study conducted on a total of 694 subjects including 148 comparison group HbAA, 208 HbSS SCD patients in steady state, 82 HbSC SCD patients in steady state, 156 HbSS SCD patients in VOC, 34 HbSC SCD patients in VOC, 34 HbSS SCD patients in post VOC, 21 HbSS SCD patients with leg ulcer and 11 HbSS SCD patients with priapism, with age ranging from 15 to 65 years. Laboratory diagnosis of SCD was done at the Sickle Cell Clinic of the Korle-Bu Teaching Hospital. Plasma nitric oxide metabolites were measured using Griess reagent system by ELISA method. RESULTS: Mean NOx of 59.66±0.75 µMol/L in the comparison group was significantly different from those in steady state (P=0.02). During VOC, there was a significant reduction in mean NOx levels to 6.08±0.81 µMol/L (P<0.001). Mean NOx levels were however, significantly higher (50.97±1.68 µMol/L) (P<0.001) in the immediate postcrisis period. The mean NOx levels in the leg ulcer (21.70±1.18 µMol/L) (P<0.001) and priapism (28.97±1.27 µMol/L) (P<0.001) patients were significantly low as compared to the SCD patients in the steady state and comparison group. CONCLUSION: This study presents the first report on plasma NOx levels in SCD complication in Ghanaian SCD patients and confirms reduced plasma NOx levels in SCD patients in general.

Reproductive endocrine issues in men with sickle cell anemia.

In patients with sickle cell anemia, the sickling of red blood cells is known to cause end-organ damage by infarction. In some men who are affected by sickle cell anemia, the obstruction of venous outflow of the penis causes priapism, which could lead to erectile dysfunction. There is also evidence that the disease is linked to other reproductive issues in men-specifically delayed puberty, low testosterone, and sperm abnormalities-although the causes of these problems are less clear. Treatment of sickle cell anemia can have effects on the reproductive system as well. This review summarizes the findings from various publications pertaining to reproductive endocrinology, along with their conclusions and discrepancies.

Hematological parameters in sickle cell anemia patients with and without priapism.

BACKGROUND: Priapism was associated with certain hematological parameters in sickle cell anemia (SCA) patients in one report but not in another. We studied differences in haematological parameters between SCA patients with and without priapism. PATIENTS AND METHODS: Eighteen patients with SCA who presented with acute priapism during the years 2001-2004 were compared with age- and sex-matched SCA patients without priapism with respect to hematocrit, reticulocyte count, level of irreversibly sickled cells (ISC), percentage of haemoglobin F (Hb F), total leukocyte and platelet counts. RESULTS: SCA patients with priapism had a mean hematocrit of 0.28 L/L, which was significantly higher than the mean hematocrit value of 0.24 L/L (P<0.05) in patients without priapism. The mean reticulocyte count of 8% in patients with priapism was significantly lower than mean reticulocyte count of 12% (P<0.05) in patients without priapism. The level of ISC of 3% in patients with priapism was significantly lower than the level of 6.5% (P<0.05) in patients without priapism. There was no statistically significant difference in the mean levels of Hb F (7% vs. 6%). Patients with priapism had a mean leukocyte count and mean platelet count that did not significantly differ from values in patients without priapism. CONCLUSIONS: SCA patients with priapism had a lower rate of hemolysis, resulting in a higher hematocrit and greater blood viscosity, which increased the risk of corpora cavernosal sickling and blockade. Hence, a relatively high hematocrit is a risk factor for the development priapism in patients with sickle cell anemia.

Men with Sickle Cell Anemia and Priapism Exhibit Increased Hemolytic Rate, Decreased Red Blood Cell Deformability and Increased Red Blood Cell Aggregate Strength.

OBJECTIVES: To investigate the association between priapism in men with sickle cell anemia (SCA) and hemorheological and hemolytical parameters. MATERIALS AND METHODS: Fifty-eight men with SCA (median age: 38 years) were included; 28 who had experienced priapism at least once during their life (priapism group) and 30 who never experienced this complication (control group). Twenty-two patients were treated with hydroxycarbamide, 11 in each group. All patients were at steady state at the time of inclusion. Hematological and biochemical parameters were obtained through routine procedures. The Laser-assisted Optical Rotational Cell Analyzer was used to measure red blood cell (RBC) deformability at 30 Pa (ektacytometry) and RBC aggregation properties (laser backscatter versus time). Blood viscosity was measured at a shear rate of 225 s-1 using a cone/plate viscometer. A principal component analysis was performed on 4 hemolytic markers (i.e., lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT), total bilirubin (BIL) levels and reticulocyte (RET) percentage) to calculate a hemolytic index. RESULTS: Compared to the control group, patients with priapism exhibited higher ASAT (p = 0.01), LDH (p = 0.03), RET (p = 0.03) levels and hemolytic indices (p = 0.02). Higher RBC aggregates strength (p = 0.01) and lower RBC deformability (p = 0.005) were observed in patients with priapism compared to controls. After removing the hydroxycarbamide-treated patients, RBC deformability (p = 0.01) and RBC aggregate strength (p = 0.03) were still different between the two groups, and patients with priapism exhibited significantly higher hemolytic indices (p = 0.01) than controls. CONCLUSION: Our results confirm that priapism in SCA is associated with higher hemolytic rates and show for the first time that this complication is also associated with higher RBC aggregate strength and lower RBC deformability.

Priapism and impotence in homozygous sickle cell disease.

A questionnaire study of Jamaican patients with homozygous sickle cell (SS) disease indicated a 42% prevalence of priapism, with a median age at onset of 21 years. Two predominantly different patterns of priapism were recorded: short "stuttering" episodes lasting less than three hours, with normal consequent sexual function, and severe prolonged attacks (generally more than 24 hours) commonly followed by impotence. Stuttering episodes were frequently a prodrome to a major attack. Over one fourth of those who had suffered priapism had some degree of impotence. Hematologic analysis indicated that priapism was significantly associated with low hemoglobin F levels and high platelet counts. Patients with severe attacks of priapism had lower hemoglobin F levels and reticulocyte count, and a higher mean corpuscular volume, than patients with only stuttering episodes. Priapism and impotence contribute to the morbidity of SS disease more frequently than previously recognized.

Is testosterone deficiency a possible risk factor for priapism associated with sickle-cell disease?

PURPOSE: The purpose of this study was to determine the association of testosterone deficiency and priapism in adult men with sickle cell disease (SCD). METHODS: A cross-sectional study of 50 adult men with SCD (hemoglobin SS) was performed. All patients had early morning blood taken for total and free testosterone, FSH, LH, prolactin, lipid levels, LDH and hematological indices. Patients completed an interviewer-administered questionnaire regarding priapism frequency, duration and treatment. Testosterone deficiency was defined as a serum total testosterone<12 nmol/L (346 ng/dL). RESULTS: The mean age of the study population was 34.2±8.9 years. Priapism was noted in 24 (48%) patients and was most frequently seen in men between ages 18-25 years. Testosterone deficiency was observed in 11 of the 50 (22%) patients, particularly in 6 of 24 (25%) patients with histories of priapism. There was no difference in mean total testosterone levels in patients with and without a history of priapism (16.7±4.9 nmol/L and 15.4±5.9 nmol/L, respectively) (p=0.43). Similarly, there was no difference in serum LH and FSH levels based on history of priapism. CONCLUSION: Testosterone deficiency is prevalent in patients with SCD; however, we did not identify an association based on a history of priapism. Larger, prospectively gathered data are needed to define the priapism profile of SCD patients with testosterone deficiency.

[Metaraminol in therapy of various forms of priapism]. / Metaraminol in der Therapie verschiedener Priapismusformen.

A total of 19 patients (aged 17-66 years) with priapism received primarily conservative treatment in the form of aspiration of blood from the cavernous bodies and subsequent intracavernous (i.c.) administration of the alpha-adrenergic drug metaraminol. In 15 patients the priapism was due to i.c. injection of vasoactive agents; 1 patient each it had developed after hemodialysis, during oral prazosin medication, and in conjunction with Fabry's disease; and in 1 patient the etiopathogenesis was unknown. Treatment of priapism with metaraminol was successful in the first 15 patients and in 2 patients with priapism due to hemodialysis and oral prazosin medication. Therapy failed in long-lasting priapism associated with Fabry's disease and in priapism of unknown etiopathogenesis. Penile detumescence took place in the first 15 patients 3 min to 2.5 h after the injection of 2-4 mg metaraminol. Hemodialysis- and prazosin-linked priapism was treated with 5 and 2 mg metaraminol, respectively; in these patients erection subsided within 15 and 4 min after onset of therapy. In a further 2 patients in whom therapy had failed Al-Ghorab shunts were constructed, with the subsequent postoperative complication of erectile impotence. Injection of metaraminol must be carried out under strict supervision of the patient's circulatory system: doses of 4 mg metaraminol or more led to an increase in blood pressure and heart rate. In 15 patients with priapism induced by i.c. application of vasoactive agents, the analysis of blood gas parameters demonstrated a severe hypercapnia (70.3 +/- 10.0 mm Hg) and acidosis (pH 7.08 +/- 0.08) 5-10 h after the onset of erection, but severe hypoxia (37.0 +/- 16.6 mm Hg) was not found until erection had lasted for more than 10 h.(ABSTRACT TRUNCATED AT 250 WORDS)