Priapism pathophysiology: clues to prevention

Burnett, Arthur L.

doi:10.1038/sj.ijir.3901077

Cited by 32 publications

(24 citation statements)

References 63 publications

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“…29 Low-flow priapism, the most common form in SCD, may be the result of venous outflow occlusion because of reduced NO availability. [30][31][32] Priapic activity and pronounced erectile responses to stimulation are seen in transgenic mice in which both neuronal (Nos1) and endothelial (Nos3) genes are knocked out and in sickle transgenic mice expressing HbS and lacking any murine hemoglobin. 33 This was a consequence of dysregulated activity of downstream signaling in the phosphodiesterase type 5 (Pde5a) pathway.…”

Section: Hemolysis and Sickle Priapism 3265mentioning

confidence: 99%

Hemolysis-associated priapism in sickle cell disease

Nolan

Wyszynski

Farrer

et al. 2005

Blood

182

150

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Priapism, although uncommon in the general population, is one of the many serious complications associated with sickle cell disease (SCD). Few studies have described the clinical and hematologic characteristics of individuals with priapism and SCD. Using data from the Cooperative Study for Sickle Cell Disease, we assembled 273 case subjects with priapism and 979 control subjects. Case subjects, compared with control subjects, had significantly lower levels of hemoglobin; higher levels of lactate dehydrogenase, bilirubin, and aspartate aminotransferase; and higher reticulocyte, white blood cell, and platelet counts. These findings suggest an association of priapism with increased hemolysis. IntroductionSickle cell disease (SCD) is an inherited condition caused by a point mutation in the ␤-globin gene (HBB), resulting in the substitution of valine for glutamic acid at position 6 of the ␤-globin chain (Glu6Val). This mutation results in the abnormal sickle hemoglobin (HbS). When deoxygenated, HbS polymerizes, damaging the sickle erythrocyte. 1 These sickle cells are short lived and can interact with endothelial cells, leukocytes, platelets, and other plasma components to initiate the vasoocclusive manifestations associated with SCD.Priapism is a sustained, painful, and unwanted erection of the penis that pathophysiologically is the result of either increased arterial inflow (ie, high flow) or, more commonly, the failure of venous outflow (ie, low flow), resulting in blood trapping within the erectile bodies. Although uncommon in the general population, 2 priapism was recognized as a serious complication of SCD as early as 1934. 3 Since then, many researchers have estimated its incidence and prevalence in various populations and the choices for its treatment. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] In general, about 30% of males with SCD under the age of 20 years reported having had at least one episode of priapism, 8,11,17 whereas frequencies of 30% to 45% are estimated for adult men. 18 Among patients with priapism, about 75% had their first occurrence before the age of 20 with the mean age being around 12 to 15 years. 17,18 Few published studies, however, have described the clinical characteristics of their participants with priapism. Using data from the Cooperative Study of Sickle Cell Disease (CSSCD), we assembled a large cohort of patients with priapism to study their clinical, laboratory, demographic, and social characteristics. Patients, materials, and methods Patient databaseThe CSSCD enrolled and followed more than 4000 patients with SCD who had visited 1 of 23 participating clinical centers across the United States between 1978 and 1998. 19,20 One of the primary aims of the CSSCD was to collect data on the clinical course of SCD from birth to death. Because of the clinical variability of SCD, data were collected on a large number of possible manifestations of the disease, including priapism. All incident events of priapism causing a participant to seek medical care were carefully recorded, ...

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Section: Hemolysis and Sickle Priapism 3265mentioning

confidence: 99%

Hemolysis-associated priapism in sickle cell disease

Nolan

Wyszynski

Farrer

et al. 2005

Blood

182

150

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“…Priapism is a condition of persistent penile erection in the absence of sexual excitation (1,2). This condition is common among males with sickle cell disease (SCD), 40% of whom display priapism (3,4).…”

Section: Introductionmentioning

confidence: 99%

Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling

Mi¹,

Abbasi²,

Zhang³

et al. 2008

J. Clin. Invest.

136

221

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Priapism, abnormally prolonged penile erection in the absence of sexual excitation, is associated with ischemia-mediated erectile tissue damage and subsequent erectile dysfunction. It is common among males with sickle cell disease (SCD), and SCD transgenic mice are an accepted model of the disorder. Current strategies to manage priapism suffer from a poor fundamental understanding of the molecular mechanisms underlying the disorder. Here we report that mice lacking adenosine deaminase (ADA), an enzyme necessary for the breakdown of adenosine, displayed unexpected priapic activity. ADA enzyme therapy successfully corrected the priapic activity both in vivo and in vitro, suggesting that it was dependent on elevated adenosine levels. Further genetic and pharmacologic evidence demonstrated that A 2B adenosine receptor-mediated (A 2B R-mediated) cAMP and cGMP induction was required for elevated adenosine-induced prolonged penile erection. Finally, priapic activity in SCD transgenic mice was also caused by elevated adenosine levels and A 2B R activation. Thus, we have shown that excessive adenosine accumulation in the penis contributes to priapism through increased A 2B R signaling in both Ada -/-and SCD transgenic mice. These findings provide insight regarding the molecular basis of priapism and suggest that strategies to either reduce adenosine or block A 2B R activation may prove beneficial in the treatment of this disorder.

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“…Priapism is defined as a prolonged and usually painful penile erection that is not initiated by sexual stimuli. While most cases of high‐flow priapism are related to penile or perineal trauma, the use of trazodone and sildenafil, and an intracavernous injection of papaverine and phentolamine, the causes of low‐flow priapism are diverse [17,18]. One‐third of low‐flow priapism patients may be idiopathic.…”

Section: Discussionmentioning

confidence: 99%

Expression and Activity of Heme Oxygenase-1 in Artificially Induced Low-Flow Priapism in Rat Penile Tissues

Jin

Gam

Jung

et al. 2008

The Journal of Sexual Medicine

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Introduction The inducible isoform of heme oxygenase (HO)-1 regulates the vascular smooth muscle tone and responds to hypoxia. Aim To investigate the role of HO-1 in a low-flow priapism. Materials and Methods Sixty male Sprague-Dawley rats were divided into five groups of six rats each. Each group of rats was sacrificed at 0 hour (group 1, control), 4 hours (group 2), 8 hours (group 3), 12 hours (group 4), and 24 hours (group 5) after inducing an artificial veno-occlusive priapism. The changes of the expression and activity of HO-1, and the expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS), and levels of cyclic guanosine monophosphate in the penis were examined in a low-flow priapism. In addition, the HO-1 expression level in the aortas from each group was simultaneously measured to determine whether the changes in HO-1 were systemic. Main Outcome Measures The expression and activity of HO-1 was examined in artificially induced veno-occlusive priapism in rat penile tissues. Results The expression of the HO-1 protein and the HO-1 enzyme activities in the penile tissues were gradually increased as time increased from 0 to 24 hours (P < 0.01). HO-1 immunoreactivities were localized in the endothelial layer of the cavernosal sinusoids. The expression of iNOS were also increased at 12 and 24 hours. The cyclic guanosine monophosphate level was also significantly increased at 24 hours (P < 0.05). However, the expression of the eNOS protein showed no statistically significant change with time, and the expression of the HO-1 protein in the aorta also showed no significant change with time. Conclusion A higher induction of HO-1 with time was observed in artificially induced veno-occlusive priapism, which might play a protective role against hypoxic injury. However, this may also play an important role in the vicious circle observed in a low-flow priapism.

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Priapism pathophysiology: clues to prevention

Cited by 32 publications

References 63 publications

Hemolysis-associated priapism in sickle cell disease

Hemolysis-associated priapism in sickle cell disease

Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling

Expression and Activity of Heme Oxygenase-1 in Artificially Induced Low-Flow Priapism in Rat Penile Tissues

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