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International Journal of Impotence Research (2003) 15, Suppl 5, S80–S85 & 2003 Nature Publishing Group All rights reserved 0955-9930/03 $25.00 www.nature.com/ijir Priapism pathophysiology: clues to prevention

AL Burnett1*

1Department of , The James Buchanan Brady Urological Institute, The Johns Hopkins Hospital, Baltimore, Maryland, USA

Priapism, in which penile persists in the absence of sexual excitation, is an enigmatic yet devastating erectile disorder. Current endeavors to manage the disorder suffer from a poor fundamental knowledge of the etiology and pathogenesis of priapism. These endeavors have remained essentially reactive, which commonly fail to avert its pathological consequences of erectile tissue damage and erectile disability, not to mention its psychological toll. The role of preventative management seems paramount with respect to priapism. As a prerequisite to formulating prevention strategies, gaining understanding of its pathogenic features and likely pathophysiologic mechanisms is viewed to be quite important. This review combined an analysis of clinicopathologic reports as well as a summary of clinical and basic science investigations on the subject to date. These assessments support the basic classification of priapism into low-flow (ischemic) and high-flow (nonischemic) hemodynamic categories, resulting from venous outflow occlusion and unregulated arterial overflow of the , respectively. In addition, consistent with the hypothesis that dysregulative physiology of penile erection accounts for some presentations of priapism, several plausible molecular mechanisms influencing the functional state of the erectile tissue are discussed. Current progress in the field suggests prevention possibilities using androgenic suppressive therapy, adrenergic agonist therapies, and effectors of the nitric oxide-dependent erection regulatory pathway in the penis. New ideas for prevention may emerge from targeting molecular mechanisms involved in regulating erectile tissue function. International Journal of Impotence Research (2003) 15, Suppl 5, S80–S85. doi:10.1038/sj.ijir.3901077

Keywords: priapism; etiology; pathogenesis; penis; erection

Introduction interventions offered subsequent to the onset of priapism are frequently inadequate emphasizes the role of prevention of the problem. However, while Priapism, defined as prolonged penile erection in the optimal therapy for this disorder may be its the absence of sexual stimulation, probably repre- prevention, the key element in this management sents the greatest challenge in therapeutic manage- practice is having a sound understanding about the ment among erectile disorders. The disorder has an pathogenic basis of the disorder. At this time, obscure etiology and often unpredictably affects scientific ignorance persists in this regard. Such select individuals without a clear pathogenic basis. fundamental questions require resolution: What Furthermore, it may cause significant physical and causes priapism? Who is most susceptible? Are psychological debilitation, commonly rendering there predisposing factors or conditions pertaining complete impotence in a young man who before its to its onset or recurrence? Is there scientific occurrence was sexually intact. Finally, treatments evidence for a pathophysiologic mechanism that offered for the disorder often are administered too can be targeted for preventive treatment? late to redress the problem fully or restore normal To advance prevention objectives, further under- erectile function. standing about the pathophysiology of priapism is Conventional treatments in the field are mostly required. Insights, both now and in the future, will reactive, administered usually after the priapic draw from clinical study as well as from basic episode has already happened. The knowledge that science investigation in this field. Clinical study relates to epidemiologic approaches as well as to observations from procedures used to treat the *Correspondence: AL Burnett, MD, The Johns Hopkins disorder. Basic science investigation relates to Hospital, 600 North Wolfe Street, Marburg 407, Baltimore, unraveling the molecular determinants of the dis- MD 21287-2411, USA. order, akin to the type of progress made recently in E-mail: [email protected] the field of . In this essay, we Priapism prevention AL Burnett S81 discuss the pathophysiology of priapism, with Table 2 Conditions associated with high-flow priapism emphasis on these subject areas. The essay con- Traumatic arteriocavernous fistula cludes with the postulate that priapism results from Vasoactive drugs derangements in the complex, integrative control Penile revascularization surgery system involved in normal penile erection, from Neurologic conditions which new preventive strategies can be considered.

hematologic dyscrasias, which are also associated Abnormal penile blood flow with tumor infiltration and obstruction from hema- togenous spread.8,9 An additional concept for priapism resulting from Frank Hinman Sr1 can be credited with providing an disturbed blood flow is high-flow, nonischemic early, comprehensive study of the pathophysiology priapism, in which arterial overflow is considered of priapism. He understood the effects of and gave to be pathogenic.12,13 Trauma seems to be the primary relevance to ‘mechanical’ disturbances primary basis for this entity, either commonly from involving the penile circulation, which he asso- blunt trauma to the or genitalia14–16 or ciated with ‘thrombosis of the veins of the corpora’. from vascular laceration such as that resulting from He identified the relationship to priapism of such needle passage with intracavernosal pharmacother- clinical conditions as pelvic abscess formation, apy17 (see Table 2). Following trauma, the penile penile tumorous growths, perineal or genital injury, vasculature is structurally damaged, which permits and hematologic dyscrasias. His description pro- uncontrolled blood entry and filling within the vided the foundation for the concept of low-flow, corpora cavernosa. Commonly, a fistula forms ischemic priapism, in which a veno-occlusive between arterial inflow vessels and the venous and pathology is believed to be a major cause of sinusoidal outflow circulation of the penis. Penile priapism. arterial revascularization surgery for arteriogenic Distinctive veno-occlusive pathologies include impotence provides another setting for the compli- (see Table 1): , which is associated cation of high-flow priapism.18,19 with sickled erythrocytes producing a sludge ef- fect;2,3 parenteral hyperalimentation particularly combined with fat emulsion, which is associated Abnormal erection neuroregulation with increased intravascular viscosity, stimulated blood coagulability, or the development of fat A ‘neural’ variant of priapism was initially sup- embolism;4,5 hemodialysis, which is associated with ported by Hinman Sr, who recognized that a increased intravascular viscosity as a consequence substantial number of patients presenting with of hemoconcentration and hypovolemia following priapism exhibit neurologic disease.1 He suggested treatment;6 intracavernosal heparin administration, that this form of priapism affected ‘erectile centers’ which is associated with increased blood coagul- of the nervous system and included infections such ability paradoxically on the basis of its stimulating as syphilis, brain tumors, epilepsy, intoxication, and platelet aggregation;7 local primary or metastatic brain and injury as causative factors.1 neoplastic processes, which are associated with Several mechanisms have been proposed to explain direct tumor infiltration and obstruction;8–11 and how these neurologic diseases cause priapism, mostly in line with concepts related to the neuror- egulatory basis for penile . One explanation Table 1 Conditions associated with low-flow priapism pertains to abnormal activation of neural reflexo- Sickle cell disease and other genic mechanisms involved in erection following Vasoactive drugs genital stimulation.20–24 Another explanation relates Neoplastic disease (local or metastatic) to disturbances in central neurotransmission that Penis 25 Urethra mediates penile erection. Knowledge of the tradi- tional autonomic sympathetic nervous system that Bladder mediates detumescence and penile flaccidity has Kidney supported the general belief that pathogenic failure Gastrointestinal tract of this system could readily predispose to the Hematologic dyscrasias 26,27 development of priapism. Polycythemia Traumatic injury Hyperlipidic parenteral nutrition Priapism variants Hemodialysis Heparin treatment Fabry’s disease Neurologic conditions Priapism variants are worth examining briefly to acknowledge that they do not readily fit the contexts

International Journal of Impotence Research Priapism prevention AL Burnett S82 of the classically described hemodynamic disorders. blunting sensory input conveyed in the dorsal nerve In addition, as unique priapism presentations, their of the penis of reflexive erectile pathways;61 oral consideration may reveal pathogenic aspects about and intracorporal alpha-adrenergic agonists, the disorder. Idiopathic priapism, which according which exert contractile effects on erectile tissue, to some investigators constitutes as much as half of thus indicating the likely pathogenic role of uncon- all registered cases,28–30 has long been recognized as trolled non-adrenergic factors;24,60,62,63 intracorpor- priapism occurring without a discernible clinical al methylene blue, an antagonist of the nitric oxide/ association. The variant has been associated with cyclic guanosine monophosphate/protein kinase G sporadic previous priapism episodes and particu- effector mechanism of corporal smooth muscle larly with erections that are sustained for prolonged relaxation, pointing to a possible pathogenic role durations of sexual activity.26,28–31 Nocturnal erec- of this biochemical pathway.64,65 tions have also been associated.1,26 ‘Stuttering’ priapism, familiarly observed as frequently recur- ring priapism episodes in men with sickle cell disease,32 has been associated with sleep and sexual Basic science investigation arousal.32–34 It is interesting that these episodes bear no relationship to other vaso-occlusive crises char- Basic research in the field has consisted mainly of acteristic of sickle cell disease35,36 and may not identifying and evaluating animal models featuring always predispose to complete erectile dysfunc- priapic behavior and molecular studies that suggest tion.32,33,35 possible mechanisms for the disorder. Transgenic Refractory priapism, in reference to the recurrent mouse models of sickle cell disease display priap- erectile state that follows aspiration or incision of ism supporting the idea that disturbed penile the corpora cavernosa for ischemic priap- vascular homeostasis associated with the hematolo- ism,2,31,37,38 has long been recognized but poorly gic disease is pathophysiologic.66 A mouse model of understood. Some have contended that the blood senility syndrome exhibits priapism, understood to flow pattern resembles high-flow priapism based on occur on the basis of degeneration of medullary radiographic study, in the absence of an arterial- reticular formation neurons that normally inhibit cavernosal fistula.37–40 High-flow priapism has been male spinal sexual reflexes.67 Mice lacking the genes clinically assessed in priapism related to medical for both neuronal and endothelial nitric oxide diseases including Fabry’s disease41 and sickle cell synthases display phasic erectile activity, indicating disease.37 Drug-induced priapism, which as sug- that the altered nitric oxide release affects the gested implies a -related phenomenon, control mechanisms associated with penile erec- represents another variant that has resulted from use tion.68 After induction of prolonged erections or of alpha-adrenergic antihypertensives, psychotropic conditions of priapism in isolated cavernosal tissue agents, , , and experimentally in animals, the cavernosal tissue pharmacotherapeutic agents for erectile dysfunc- loses responsiveness to adrenergically stimulated tion.42–56 The mechanism of action is contended to tissue contraction,69,70 undergoes destructive meta- relate to peripheral and central signaling pathways bolism via lipid peroxidation,71 and increases stimulated by the offending drug that produce expression of the tissue fibrosis marker transforming corporal smooth muscle relaxation. growth factor beta.72

Clinical study Dysregulatory mechanisms Besides observations of drug effectors of priapism, clinical assessments of the corrective effects of Since many regulatory factors are now known to therapeutic prospects for the disorder have contrib- influence the functional state of the cavernosal uted to understanding its pathophysiology. Pharma- tissue, it is not surprising to consider that situations ceutical approaches described to offer benefit in which any of these factors go awry may lead to the include: intracorporal thrombolytic agents, which development of priapism. This reference to erectile would support the pathogenic roles of blood stasis regulatory factors involved in priapism could apply and thrombosis,57,58 oral , which to factors involved in corporal smooth muscle by exerting antiandrogenic effects would imply that responses that operate somehow in a dysfunctional androgens permit aberrant penile erection;35 sys- manner or to factors activated under the pathologi- temic injections of gonadotropin-releasing hormone cal conditions of priapism that adversely affect analogues, which because they are also anti-andro- erectile tissue physiology. Dysregulatory mechan- genic would further hypotheses about the patho- isms of erectile tissue function may be associated genic role of androgens;59,60 lidocaine as a penile with idiopathic, stuttering, and other divergent anesthetic block, which is considered to work by presentations of priapism, conceivably distin-

International Journal of Impotence Research Priapism prevention AL Burnett S83 guished from the origins of classic hemodynamic predictable pattern of progression to erectile tissue types of priapism. destruction in which, it would seem, clinical The current description of mediators and signal opportunities exist to gain disease control. Pre- transduction pathways involved in penile erection sently, current pharmacologic treatment successes suggests several scientifically plausible mechanisms support the roles of androgenic suppressive that may contribute to the pathophysiology of agents,59,60 adrenergic agonist therapies,24,60,62,63 priapism. Such mechanisms include: physiologic and effectors of the nitric oxide-dependent erection increases in oxygen tension within the cavernosal regulatory pathway in the penis such as methylene tissue, which stimulate corporal smooth muscle cell blue.64,65 As promising as these therapies have been, production and release of vasorelaxant substances they still warrant certain considerations such as while inhibiting the production and release of when they should be administered, whether they vasoconstrictive substances;73,74 heightened andro- can be administered with minimal penile trauma genic milieu, which promotes corporal neuromus- and without causing adverse extra-penile effects, cular transmission of penile erection;75 altered and whether they can be offered with a regimen that composition of myosin isoforms and the extent of does not impair natural erections long term. myosin phosphorylation in the corporal smooth For the future, systematic development and musculature, which determines its level of basal application of therapies may result from improved tone;76,77 abnormal expression levels of ion chan- understanding of the role of dysregulatory mechan- nels and gap junctions in corporal smooth muscle isms of penile erection. This charge is consistent cells, which could affect the tonicity and synchro- with current objectives to better understand the nicity of these cells;78 aberrant nitric oxide regula- molecular mechanisms associated with the erectile tion in the penis, which has been correlated with tissue response. Therapies are anticipated that will supraphysiologic erectile responses;68,79 intracor- target mechanisms involved in neurovascular trans- poral blood flow-related ‘shear stress’ forces that mission unique to the penis, corporal smooth activate endothelial-based biochemical pathways muscle physiology, and biochemical regulation of sustaining penile erection.80 erectile responses.

Prevention strategies References The development of prevention strategies for priap- ism expectedly will revolve around surveillance and 1 Hinman F. Priapism. Ann Surg 1914; 60: 689 – 716. early implementation of effective therapies. Indivi- 2 Hinman Jr F. Priapism; reasons for failure of therapy. J Urol duals at risk for ischemic priapism, such as the 1960; 83: 420 – 428. 3 Hasen HB, Raines SL. Priapism associated with sickle cell hemodialysis patient or the patient with a hemato- disease. J Urol 1962; 88: 71 – 76. logic dyscrasia, should be cautioned about the 4 Klein EA, Montague DK, Steiger E. Priapism associated with possible occurrence of the disorder under these the use of intravenous fat emulsion: case reports and circumstances while understandably basic attempts postulated pathogenesis. J Urol 1985; 133: 857 – 859. 5 Hebuterne X, Frere AM, Bayle J, Rampal P. Priapism in a are undertaken to remedy the presumed causative patient treated with total parenteral nutrition. J Parenter etiology. Given the high level of alertness under Enteral Nutr 1992; 16: 171 – 174. these circumstances, standard therapies for manage- 6 Fassbinder W et al. Factors predisposing to priapism in ment of the veno-occlusive pathology should be haemodialysis patients. Proc Eur Dial Transplant Assoc readily available. The risk of priapism with vasoac- 1976; 12: 380 – 386. 7 Bschleipfer T et al. Heparin-induced priapism. Int J Impot Res tive pharmacotherapy for erectile dysfunction 2001; 13: 357 – 359. should be reduced with proper counseling regarding 8 Chan PTet al. Priapism secondary to penile metastasis: a report this risk and considerations for in-office test dosing, of two cases and a review of the literature. J Surg Oncol 1998; particularly for local or combined pharmacothera- 68: 51 – 59. 9 Morano SG et al. Treatment of long-lasting priapism in chronic pies, to establish the best dose that would limit the myeloid leukemia at onset. Ann Hematol 2000; 79: 644 – 645. risk subsequently. 10 Morga Egea JP et al. Metastasis priapism. Report of 4 new cases Notwithstanding cases of unprecedented is- and review of the literature. Arch Esp Urol 2000; 53: 447 – 452. chemic priapism, high-risk groups such as those 11 Hettiarachchi JA et al. Malignant priapism associated with with sickle cell disease manifesting ‘stuttering’ metastatic urethral carcinoma. Urol Int 2001; 66: 114 – 116. 12 Burt GB, Schirmer HK, Scott WW. A new concept in the priapism and those exhibiting recurrent ‘idiopathic’ management of priapism. J Urol 1960; 83: 60 – 61. or neurologic priapism may be considered to have 13 Hauri D, Spycher M, Bru¨hlmann W. Erection and priapism: a the greatest relevance for prevention efforts. These new physiopathological concept. Urol Int 1983; 38: 138 – 145. presentations arguably constitute the most clinically 14 Ricciardi Jr R et al. Delayed high flow priapism: pathophysiol- ogy and management. J Urol 1993; 149: 119 – 121. vexatious settings for priapism and would seem to 15 Winter CC, McDowell G. Experience with 105 patients with benefit most from taking advance measures against priapism: update review of all aspects. J Urol 1988; 140: the disorder. After all, these individuals fit a 980 – 983.

International Journal of Impotence Research Priapism prevention AL Burnett S84 16 Llado J, Peterson LJ, Fair WR. Priapism of the proximal penis. 43 Siegel S, Streem SB, Steinmuller DR. -induced J Urol 1980; 123: 779 – 780. priapism. Pathogenic and therapeutic implications. Br J Urol 17 Witt MA et al. Traumatic laceration of intracavernosal : 1988; 61: 165. the pathophysiology of nonischemic high flow arterial priap- 44 Vaidyanathan S et al. Prolonged penile erection association ism. J Urol 1990; 143: 129 – 132. with in a cervical patient. Spinal 18 Michal V et al. Vascular surgery in the treatment of impotence; Cord 1998; 36: 805. its present possibilities and prospects. Czech Med 1980; 3: 45 Abber JC et al. Priapism induced by and 213 – 217. : mechanism of action. J Urol 1987; 137: 1039 – 1042. 19 Jarow JP, DeFranzo AJ. Hypervascularity of the 46 Carson III CC, Mino RD. Priapism associated with trazodone following arterialization of the dorsal vein. J Urol 1992; 147: therapy. J Urol 1988; 139: 369 – 370. 706 – 708. 47 Segraves RT. Effects of psychotropic drugs on human erection 20 Wasmer JM, Carrion HM, Mekras G, Politano VA. Evaluation and ejaculation. Arch Gen Psychiatry 1989; 46: 275 – 284. and treatment of priapism. J Urol 1981; 125: 204 – 207. 48 Saenz de Tejada I et al. Pathophysiology of prolonged penile 21 Chin JL, Sharpe JR. Priapism and anesthesia: new considera- erection associated with trazodone use. J Urol 1991; 145: tions. J Urol 1983; 130: 371. 60 – 64. 22 Van Arsdalen KN, Chen JW, Smith MJV. Penile erections 49 Seftel AD et al. -associated priapism: a case report. complicating transurethral surgery. J Urol 1983; 129: 374 – 376. J Urol 1992; 147: 146 – 148. 23 Shantha TR, Finnerty DP, Rodriquez AP. Treatment of 50 Kulmala R, Lehtonen T, Nieminen P, Tammela T. Aetiology of persistent penile erection and priapism using terbutaline. J priapism in 207 patients. Eur Urol 1995; 28: 241 – 245. Urol 1989; 141: 1427 – 1429. 51 Virag R. About pharmacologically induced prolonged erec- 24 Dittrich A, Albrecht K, Bar-Moshe O, Vandendris M. Treat- tion. Lancet 1985; 1: 519 – 520. ment of pharmacological priapism with . J Urol 52 Halsted DS, Weigel JW, Noble MJ, Mebust WK. - 1991; 146: 323 – 324. induced priapism: 2 case reports. J Urol 1986; 136: 109 – 110. 25 Steers WD. Neural pathways and central sites involved in 53 Lomas GM, Jarow JP. Risk factors for papaverine-induced penile erection: neuroanatomy and clinical implications. priapism. J Urol 1992; 147: 1280 – 1281. Neurosci Biobehav Rev 2000; 24: 507 – 516. 54 Lue TF. Priapism after transurethral alprostadil. J Urol 1999; 26 Levine FJ, Saenz de Tejada I, Payton TR, Goldstein I. Recurrent 161: 725 – 726. prolonged erections and priapism as a sequela of priapism: 55 Bettocchi C, Ashford L, Pryor JP, Ralph DJ. Priapism after pathophysiology and management. J Urol 1991; 145: 764 – 767. transurethral alprostadil. Br J Urol 1998; 81: 926. 27 Melman A, Serels S. Priapism. Int J Impot Res 2000; 12: S133 – 56 Sur RL, Kane CJ. citrate-associated priapism. S139. Urology 2000; 55: 950. 28 Nelson III JH, Winter CC. Priapism: evolution of management 57 Gibel LJ, Reiley E, Borden TA. Intracorporeal cavernosa in 48 patients in a 22-year series. J Urol 1977; 117: 455 – 458. streptokinase as adjuvant therapy in the delayed treatment 29 Larocque MA, Cosgrove MD. Priapism: a review of 46 cases. J of idiopathic priapism. J Urol 1985; 133: 1040 – 1041. Urol 1974; 112: 770 – 773. 58 Rutchik S, Sorbera T, Rayford RW, Sullivan J. Successful 30 Pohl J, Pott B, Kleinhans G. Priapism: a three-phase concept of treatment of recalcitrant priapism using intercorporeal injec- management according to aetiology and prognosis. Br J Urol tion of tissue plasminogen activator. J Urol 2001; 166: 628. 1986; 58: 113 – 118. 59 Levine LA, Guss SP. Gonadotropin-releasing hormone analo- 31 Lue TF, Hellstrom WJG, McAninch JW, Tanagho EA. Priapism: gues in the treatment of sickle cell anemia-associated priap- a refined approach to diagnosis and treatment. J Urol 1986; ism. J Urol 1993; 150: 475 – 477. 136: 104 – 108. 60 Mantadakis E et al. Outpatient penile aspiration and epinephr- 32 Emond AM, Holman R, Hayes RJ, Serjeant GR. Priapism and ine irrigation for young patients with sickle cell anemia and impotence in homozygous sickle cell disease. Arch Intern Med prolonged priapism. Blood 2000; 95: 78 – 82. 1980; 140: 1434 – 1437. 61 Seftel AD, Resnick MI, Boswell MV. Dorsal nerve block for 33 Fowler Jr JE, Koshy M, Strub M, Chinn SK. Priapism management of intraoperative penile erection. J Urol 1994; associated with the sickle cell hemoglobinopathies: preva- 151: 394 – 395. lence natural history and sequelae. J Urol 1991; 145: 65 – 68. 62 Sayer J, Parsons CL. Successful treatment of priapism with 34 Hamre MR et al. Priapism as a of sickle cell intracorporeal epinephrine. J Urol 1988; 140: 827. disease. J Urol 1991; 145: 1–5. 63 Molina L, Bejany D, Lynne CM, Politano VA. Diluted 35 Serjeant GR, De Ceulaer K, Maude GH. Stilboestrol and epinephrine solution for the treatment of priapism. J Urol stuttering priapism in homozygous sickle-cell disease. Lancet 1989; 141: 1127 – 1128. 1985; 1274 – 1276. 64 Steers WD, Selby Jr JB. Use of methylene blue and selective 36 Tarry WF, Duckett Jr JW, Snyder III HM. Urological complica- embolization of thepudendal for high flow priapism tions of sickle cell disease in a pediatric population. J Urol refractory to medical and surgical treatments. J Urol 1991; 146: 1987; 138: 592 – 594. 1361 – 1363. 37 Ramos CE, Park JS, Ritchey ML, Benson GS. High flow 65 Martı´nez Portillo FJ et al. Methylene blue as a successful priapism associated with sickle cell disease. J Urol 1995; 153: treatment alternative for pharmacologically induced priapism. 1619 – 1621. Eur Urol 2001; 39: 20 – 23. 38 Seftel AD et al. High flow priapism complicating veno- 66 Beuzard Y. Transgenic mouse models of sickle cell disease. occlusive priapism: pathophysiology of recurrent idiopathic Curr Opin Hematol 1996; 3: 150 – 155. priapism? J Urol 1998; 159: 1300 – 1301. 67 Adams DD et al. A mouse genetic locus with death clock and 39 Matson S, Herndon CDA, Honig SC. Pathophysiology of ‘low life clock features. Mech Ageing Dev 2001; 122: 173 – 189. flow’ priapism: intermediate phaseFevidence of ‘high flow’ 68 Palese MA, Johns DG, Crone JK, Burnett AL. Priapic activity in defined with duplex ultrasonography. Int J Impot Res 1999; mice lacking neuronal and endothelial nitric oxide synthase 11: S79 (abstract B6). genes. J Urol 2002; 167: 238 (abstract 936). 40 Hakim LS et al. Evolving concepts in the diagnosis and 69 Broderick GA, Gordon D, Hypolite J, Levin RM. Anoxia and treatment of arterial high flow priapism. J Urol 1996; 155: corporal smooth muscle dysfunction: a model for ischemic 541 – 548. priapism. J Urol 1994; 151: 259 – 262. 41 Foda MM et al. High-flow priapism associated with Fabry’s 70 Saenz de Tejada I et al. Acidosis impairs rabbit trabecular disease in a child: a case report and review of the literature. smooth muscle contractility. J Urol 1997; 157: 722 – 726. Urology 1996; 48: 949 – 952. 71 Evliyaoglu Y, Kayrin L, Kaya B. Effect of allopurinol on lipid 42 Rubin SO. Priapism as a probable sequel to medication. Scand peroxidation induced in corporeal tissue by veno-occlusive J Urol Nephrol 1968; 2: 81 – 85. priapism in a rat model. Br J Urol 1997; 80: 476 – 479.

International Journal of Impotence Research Priapism prevention AL Burnett S85 72 Ul-Hasan M et al. Expression of TGF-(-1 mRNA and 76 DiSanto ME et al. Expression of myosin isoforms in smooth ultrastructural alterations in pharmacologically induced pro- muscle cells in the . Am J Physiol longed penile erection in a canine model. J Urol 1998; 160: 1998; 275: C976 – C987. 2263 – 2266. 77 Chitaley K, Webb RC, Mills TM. RhoA/Rho-kinase: a novel 73 Moreland RB. Pathophysiology of erectile dysfunction: player in the regulation of penile erection. Int J Impot Res the contributions of trabecular structure to function and 2001; 13: 67 – 72. the role of functional antagonism. Int J Impot Res 2000; 12: 78 Christ GJ et al. Ion channels and gap junctions: their role in S39 – S46. erectile physiology dysfunction and future therapy. Mol Urol 74 Moreland RB et al. O2-dependent prostanoid synthesis 1999; 3: 61 – 73. activates functional PGE receptors on corpus cavernosum 79 Burnett AL et al. Noncholinergic penile erection in mice smooth muscle. Am J Physiol Heart Circ Physiol 2001; 281: lacking the gene for endothelial nitric oxide synthase. J Androl H552 – H558. 2002; 23: 92 – 97. 75 Zargooshi J. Priapism as a complication of high dose 80 Hurt KJ et al. Akt-dependent phosphorylation of endothelial testosterone therapy in a man with hypogonadism. J Urol nitric-oxide synthase mediates penile erection. Proc Natl 2000; 163: 907. Acad Sci U S A 2002; 99: 4061 – 4066.

International Journal of Impotence Research