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International Journal of Impotence Research (1997) 9, 149±153 ß 1997 Stockton Press All rights reserved 0955-9930/97 $12.00 Cavernous oxygen tension in the patients with erectile dysfunction È zguÈl and O È CanguÈven F Tarhan, U KuyumcuogÏlu, A Kolsuz, A O Urology Clinic, Kartal Education and Research Hospital, Istanbul, Turkey We designed a study consisting of 27 consecutive patients with erectile dysfunction in order to evaluate the role of cavernous oxygen tension. Patients were completely evaluated by history, physical examination, multiple blood analyses, serum testosterone level measurements, papaverine test, color duplex sonography and dynamic infusion cavernosometry-cavernosography. Blood gas samples were obtained from femoral artery and corpus cavernosum before drug injection and also from corpus cavernosum at 5, 10, 20, 30, 40min following drug injection. Aetiologic classi®cation of erectile dysfunction in our patients was as follows: psychogenic in 8, cavernosal failure in 14 and arterial disease in 5 cases. At ¯accidity, no signi®cant differences were found in the mean pO2, sO2, pCO2 and pH values of patient groups. After injection of intracavernous papaverine, results of the cavernous pO2 (P < 0.05), sO2 (P < 0.05) levels were found to be statistically signi®cantly different between patients with vascular and psychogenic erectile dysfunction. Analysis of maximal cavernosal oxygen tension and PSV revealed statistically signi®cant correlation (r 0.66, P < 0.001). The results of this study suggest that changes in arterial and cavernosal pO2 and sO2 values may be contributing factors or co-factors in erectile failure. Keywords: corpus cavernosum; erection; oxygen; erectile dysfunction; papaverine Introduction Penile erection and detumescence are complex events and require intact vascular structure, endothelium, smooth muscle and nerves.1 In the ¯accid state, cavernosal smooth muscle tone is high and cavernous arteries are relatively contracted. At the initiation of erection, cavernous smooth muscles and arterioles relax and arterial blood ¯ow into corpora cavernosa increases, which is immediately re¯ected in the level of oxygenation rising from mixed venous levels to those of arterial blood.2±4 Cavernous smooth muscle compliance increases and the sinusoids distend, compressing the subtunicular venular plexus against the tunica albuginea and restricting venous out¯ow.1 It was noted previously that the basal tone of corporeal smooth muscle as well as the evoked response to stimulation depends on the state of oxygenation.5 Physiological concentrations of oxygen modulate penile erection by regulating nitric oxide (NO) synthesis in penile corpus cavernosum tissue.2 Low oxygen tension inhibits the release of Correspondence: Dr F Tarhan, TophaneliogÏlu Cad. Murat È skuÈdar, Istanbul, Sitesi, G Blok 92/18, TR-81190 C Ë amlica-U Turkey. Received 20 February 1996; revised/accepted 3 December 1996 the NO and NO synthetase activity in penile corpus cavernosum regardless of the normal or pathological state of the nerves and endothelium.2 Vascular disorders in cavernous arteries measured by color duplex sonography may be a sign of progressive disease. Erectile dysfunction may be related to cavernosal smooth muscle malfunction, besides impaired ¯ow in the cavernous arteries.6,7 Blood ¯ow in the normal range by color duplex sonography can not rule out cavernous malfunction since there may still be abnormal oxygenation of corpus cavernosum. The purpose of this study is to determine whether there is a role of cavernous oxygen tension in the aetiology of erectile dysfunction by evaluating systemic and cavernosal blood analysis and color duplex sonography. Patients and methods Twenty-seven unselected patients with complaints of erectile dysfunction, who came to our clinic between February 1995 and November 1995, were included in this study. After written informed consent, each patient underwent comprehensive evaluation consisting of a detailed history, physical examination, psychiatric counseling, blood chemistry panel (SMA 12), testosterone level determina- Oxygen tension and corpus cavernosum F Tarhan et al 150 Table 1 Results of femoral artery blood gas analyses in 27 patients Mean Mean Mean Mean Mean * age (y) PO2 (mmHg) SO2 (%) PCO2 (mmHg) pH Psychogenic Arterial disease Venous failure 38.4 6.5 99.0 0.7 98.3 0.3 35.1 1.1 7.4 0.01 58.4 3.1 87.2 5.2** 96.4 0.7 38.0 2.0 7.4 0.01 51.9 4.9 91.2 1.8* 96.9 0.3 38.9 1.1 7.4 0.01 Between psychogenic and arteriogenic groups P < 0.05. Between psychogenic and venogenic groups P < 0.001. ** tions, an intracavernosal drug injection test (60mg papaverine) and penile blood ¯ow studies by color duplex sonography. Additionally dynamic infusion cavernosometry-cavernosography (DICC) (Cavropump, Lifetec, USA) was performed in some patients. The erectile response to intracavernosal drug injections were categorized from E0 to E3 by a designated physician following inspection and palpation (E0: No erection, E1: Only tumescence, E2: Tumescence and partial rigidity, E3: Full erection). Erections graded as E2 or E3 were considered adequate for intercourse. Blood gas samples (1ml with 25 USP units/ml Na Heparine) were obtained from femoral artery and corpus cavernosum before drug injection and also from corpus cavernosum 5, 10, 20, 30, 40 mins. following drug injection. pO2, sO2, pCO2 and pH were evaluated by Gem-Stat (USA) blood chemistry analyzer. Blood pO2, pH were measured by polarographic and pCO2 by potantiometric methods. Cutoff values of normal systemic pO2, sO2 and pCO2 were set at 90 mmHg, 94% and 40 mmHg, respectively.8 Penile blood ¯ow studies were carried out with a Toshiba (270 SSA-270HG) 7.5 mHz probe following intracavernosal injection of 60 mg papaverine. Peak systolic velocity (PSV), increase in diameter and end diastolic velocity (EDV) of deep penile arteries were determined just before and until 30 min after the intracavernosal injections. Cutoff values for PSV, increase in diameter and EDV in deep arteries of the corpus cavernosum were set at 30 cm/s, 70%, and 5cm/s, respectively. A maintenance ¯ow value greater than 30 ml/s, initial decompression of corporeal pressure greater than 40 mmHg and a postinfusion steady state pressure less than 50 mmHg during DICC following 60 mg papaverine injection were the criteria for cavernosal insuf®ciency. Results are expressed as mean values s.e.m. Mann-Whitney U test and Spearman correlation analysis were used for statistical analyses. Results The age of 27 patients ranged from 20±70 (49.1 3.2) years; the duration of their erectile dysfunction varied between 10 months and 8 years (18.3 6.4 months). Aetiologic classi®cation of erectile dysfunction in the 27 patients was as follows: psychogenic in 8 cases (29.6%), cavernosal failure in 14 cases (51.9%) and arterial disease in 5 cases (18.5%). Medical histories of the 19 patients with vascular pathologies revealed diabetes mellitus in 5 cases (26.3%), hypertension in 4 cases (21.1%), coronary heart disease in 3 cases (15.8%) and chronic obstructive pulmonary disease in one case (5.3%). The erectile response to intracavernosal papaverine in 27 patients was as follows: E3 in 8 cases (29.6%), E2 in 6 cases (22.2%), E1 in 10 cases (37.1%) and E0 in 3 cases (11.1%). After intracavernous injection of 60 mg papaverine, PSV in the cavernous arteries of the 27 patients were between 22 and 70 cm/s. In 22 men (81.5%) PSV exceeded 30 cm/s. Mean femoral artery pO2, sO2, pCO2 and pH values of patients are shown in Table 1. The mean femoral pO2 and sO2 values in the psychogenic group were signi®cantly different from those of the arteriogenic (P < 0.05) and the venogenic (P < 0.001) groups. The mean pH and pCO2 values were not statistically different between these patient groups (P > 0.05). The femoral artery pO2 values were less than 90 mmHg in 3 (60.0%) of 5 patients with arterial disease and in 6 (42.9%) of 14 patients with corporeal failure and were greater than 90 mmHg in all 8 patients (100%) with psychogenic erectile dysfunction. The femoral artery pCO2 results were greater than 40 mmHg in 7 (36.8%) of 19 patients with organic erectile dysfunction and within normal limits in all 8 patients (100%) with psychogenic erectile dysfunction. The femoral artery sO2 and pH levels of all patients were within normal ranges. During ¯accidity, the mean cavernous pO2, sO2, and pH values were lower than femoral artery blood and the mean cavernous pCO2 levels were higher (Figures 1 and 2). Before the intracavernosal papaverine injection, no signi®cant difference was observed between the mean cavernous pO2, sO2, pH and pCO2 values of the patients with arteriogenic, venogenic and psychogenic erectile dysfunction (P > 0.05). The cavernous pO2, sO2 values increased and pH and pCO2 values decreased after injection of papaverine (Figures 1 and 2). Oxygen tension and corpus cavernosum F Tarhan et al 151 Figure 1 Comparison of time-related pO2 (a) and sO2 (b) analysis results in 27 patients with arterial disease (uÐu), cavernosal failure (nÐn) and psychogenic erectile dysfunction (sÐs). At 5, 10 and 40 mins. following injection of intracavernous papaverine, results of the cavernous pO2 and sO2 of the patients in psychogenic and arteriogenic groups were found to be statistically signi®cantly different (P < 0.05). The cavernous pO2 levels were also statistically different at 40 mins. following papaverine injection in the patients with psychogenic and venogenic erectile dysfunction (P < 0.05). Additionally, cavernous sO2 levels were different at 10 mins. following papaverine injection comparing the patients in the psychogenic and venogenic groups (P < 0.05). Cavernosal blood pCO2 and pH levels were not different after papaverine injection in the patient groups (P > 0.05). Correlation analysis of maximal cavernosal oxygen tension and PSV (r 0.66, P < 0.001) was statistically signi®cant (Figure 3), and sO2/PSV (r 0.07, P > 0.05) correlation was not found to be statistically signi®cant. Figure 2 Comparison of time-related pCO2 (a) and pH (b) analysis results in 27 patients with arterial disease (uÐu), cavernosal failure (nÐn) and psychogenic erectile dysfunction (sÐs). Discussion Studies have shown that intracavernosal blood in the ¯accid penis contains low pO2 similar to venous blood.2,3,9,10 In the penile tumescence phase, parasympathetic stimulation or intracavernosal injection of drugs enhances intracavernosal pO2 to arterial levels by increased blood ¯ow.2±4,9,10 At these pO2 levels, autonomic dilator nerves and the endothelium are able to synthesize NO mediating cavernosal smooth muscle relaxation that is necessary for penile erection.2 A possible relationship between NO and pO2 was demonstrated; the synthesis of NO requires O2 as a substrate and NO synthetase activity is inhibited at low pO2.2 Arterial pO2 values in both arteriogenic and venogenic groups were statistically signi®cantly lower compared to the psychogenic group in our study. This was also supported by Sattar et al11 who Oxygen tension and corpus cavernosum F Tarhan et al 152 Figure 3 Correlation between maximal cavernosal oxygen tension and PSV (r 0.66, P < 0.001) in 27 patients with erectile dysfunction. found the cavernous-brachial oxygen tension index in the psychogenic group to be signi®cantly different from that of the venogenic and arteriogenic groups. Systemic diseases and advanced age may account for the low arterial pO2 levels found in groups with organic aetiology. Although these ®ndings may be expected in the group with arterial disease, surprisingly, arterial pO2 values were found as low in some patients with venous failure. For this reason, cavernosal blood pO2 as well as systemic blood pO2 analyses must be performed in patients with organic aetiology. Cavernous-brachial oxygen tension index suggested by Sattar et al11 can be used as a quantitative method. Low arterial blood pO2 by inadequate relaxation of cavernosal smooth muscle simulates organic erectile dysfunction. Erectile dysfunction may be reversed by increasing arterial pO2 in some patients with low arterial blood pO2.12 If we had not performed systemic arterial blood gas analysis in this study, we would have concluded that abnormal cavernosal blood gas values re¯ect a local disease. Since the results of concomitant systemic arterial blood gas analyses were not mentioned in previous studies on this subject, it is not known whether abnormal cavernosal pO2 results in patients with organic aetiology re¯ect a systemic disease or not. The clinical and experimental studies showed that O2 tension can be used to monitor the local arterial in¯ow to corpus cavernosum.9,10 Critical value of cavernous pO2 for impaired cavernous perfusion was reported to be about 50±65 mmHg.2,10 Knispel and Andresen10 reported that the erectile response after intracavernosal PGE1 was not correlated with the slope of increase in oxygen tension, and PSV and maximal pO2 of corpus cavernosum correlated well in 71% of the patients, however, we observed a correlation between maximal oxygen tension of corpus cavernosum and PSV. Results of cavernosal blood gas analyses in this study is supported by several studies.3,4,9,10,11,13 Sattar et al11 reported that after injection of PGE1, the mean cavernous pO2 in the control group was signi®cantly different from that in the venogenic and the arteriogenic groups. Furthermore, our data reveal that the femoral artery pO2 results as well as cavernous pO2 and sO2 results following intracavernosal papaverine injection were different in patients with organic erectile dysfunction compared to patients with psychogenic erectile dysfunction. Since papaverine has acidic pH ( < 4.0), the mean cavernous pH values decreased after injection of papaverine. Although, it is said that papaverine may have signi®cant in¯uence on cavernous blood gas analyses,14 our results of cavernous pO2 is similar to results of electroerection, visual-tactile sexual stimulation and intracavernosal injection of the PGE13,10,13 which have no adverse effects on cavernous pH. It was previously demonstrated that inhibition of complete corporeal smooth muscle relaxation has a role in erectile dysfunction with advancing age and corporeal failure.6,7 Furthermore, it was noted that O2 tension in¯uenced corporeal smooth muscle tone.5 We also concluded that low O2 tension affects the corporeal smooth muscle tone as mentioned above. Systemic or local hypoxia may cause erectile dysfunction in a short time period probably due to its effect on the synthesis of cavernous NO2 and/or cavernous smooth muscle tone.5 It was con®rmed that reversal of erectile dysfunction follows increase in arterial pO2 during long term O2 therapy in patients with chronic obstructive pulmonary disease.12 In a long-time period, hypoxia may cause erectile dysfunction by increased TGF-b1 expression leading to extracellular matrix deposition and eventually ®brosis.15 This idea was supported by a study observing a signi®cant correlation between cavernosal pO2 values and cavernous smooth muscle content.11 Although, results of this study is not suf®cient to point out a clear cut conclusion due to small number of cases, changes of arterial and cavernosal pO2 and sO2 values may be contributing factors or co-factor in the erectile failure. Acknowledgement Authors thank Dr Petek AriogÏlu for the language edition. References 1 Anderson KE. 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