| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Urology, New York University School of Medicine, New York, New York.
| Correspondence to: Dr Andrew McCullough, New York University School of Medicine, Department of Urology, 150 East 32 Street, New York, NY 10012 (e-mail: andy.mccullough{at}nyumc.org). |
| Received for publication July 27, 2006; accepted for publication September 18, 2006. |
 |
Abstract |
|---|
 Top Abstract Materials and MethodsResultsDiscussionConclusionsReferences |
|---|
Key words: Corporal oxygen saturation, tissue oximeter
Oxygenation of the cavernous tissue is important in regulation of local mechanisms of erection. Blood flow arterialization during erections is felt to be crucial in providing the free oxygen necessary for formation of NO by neuronal and endothelial nitric oxide synthase. Low oxygen tension inhibits NO synthetase activity and the release of NO in penile corpus cavernosum regardless of the normal or physiological state of the nerves and endothelium. The lack of free oxygen, transported to the penis by hemoglobin, is theoretically detrimental to the synthesis of NO and cGMP formation. Corporal hypoxia predisposes to cavernous fibrosis from the increased synthesis of collagen via TGF beta, resulting in erectile dysfunction (ED).
Limited invasive blood gas studies in human models have shown decreased oxygen tension in vasculogenic impotence and a hypoxic cavernosal state in the flaccid penis. Kim et al (1993, 1996) showed that isolated human and rabbit corpus cavernosum tissue strips exposed to arterial-like partial pressure of oxygen (pO2) relaxed with acetylcholine and to electrical stimulation of the autonomic dilator nerves. Decreasing pO2 to levels measured in the flaccid penis resulted in loss of the relaxation responses. Normoxic conditions readily restored endothelium-dependent and neurogenic relaxation. In the rabbit corpus cavernosum, low pO2 reduced basal levels of cGMP and prevented cGMP accumulation induced by stimulation of dilator nerves. Furthermore, low pO2 inhibited nitric oxide synthase activity in corpus cavernosum cytosol. It was concluded that physiological concentrations of oxygen modulate penile erection by regulating nitric oxide synthesis in corpus cavernosum tissue (Kim et al, 1993, 1996).
One theory is that progressive erectile dysfunction occurs due to the loss of rapid eye movement (REM) nocturnal penile tumescence (NPT). Whereas men without ED will demonstrate erectile activity for as much as 60% of their sleep time, men with ED have been shown to lose NPT. This loss of NPT occurs with numerous pathologic processes. This is seen with aging and in disease states, such as diabetes, hypogonadism, and radical pelvic surgery (Karacan et al, 1978, 1989). A dramatic loss of NPT is seen after a radical prostatectomy, due to denervation or nerve damage (McCullough, 2001; Padma-Nathan et al, 2004). Penile shrinkage, muscular atrophy, and associated penile tissue apoptosis and fibrosis have been documented in the animal model and in humans after cavernous nerve damage (Klein et al, 1997; Fraiman et al, 1999; User et al, 2003; Schwartz et al, 2004). The chronically flaccid state theoretically results in a chronic state of penile hypoxia.
The painful, invasive nature of blood gas determination has limited the accrual of normative data on penile oxygen saturation (StO2) levels in the flaccid and erect state in potent men and in men with or without ED. It has never been shown that men with ED have a chronic state of oxygen desaturation or a lower resting oxygen saturation state. The objective of this study was to noninvasively determine the StO2 levels in men with and without ED in the flaccid and erect states through the use of Optical Diffusion Imaging and Spectroscopy (ODIS) with the ODISsey Tissue Oximeter (Odissey).
|
Materials and Methods |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
Men undergoing diagnostic/therapeutic MUSE applications or PGE-1 penile injections as part of their treatment had additional StO2 measurements 10 to 15 minutes after the instillation of vasoactive material. No additional office visits were planned for measurements. Demographic data including age, race, partner status, comorbidities, surgeries, medications, and endothelial risk factors (diabetes, smoking, hypertension, hyperlipidemia, depression) were recorded.
Penile StO2 measurements were performed with the use of a tissue oximeter, Odissey (Figure 1). The Odissey is based on optical diffusion infrared spectroscopy, ODIS. ODIS is a patent-protected, noninvasive method of characterizing tissue StO2 based on measurements of photon scattering and absorption. It is achieved by sending optical signals (continuous wave, pulse, or intensity-modulated wave) into tissue and measuring the corresponding diffuse reflectance or transmittance on the tissue surface. Absorption is caused by interaction with chromophores, which are light-absorbing units of tissue. Hemoglobin is one of the principal chromophores in tissue. Evaluation of reflected light gives clinical information about the biochemical status of these chromophores (Xu et al, 2003).
|
Each patient had a minimum of 5 measurements taken at 5 sites (right thigh, right corpora, mid-glans, left corpora, left thigh) using the hand-held probe (Figure 2). Thigh measurements were included as controls. A subset of 64 patients had prostaglandin E-1 urethral suppository or injections (PGE1) administered, with repeat StO2 measurements (after 10 minutes) as part of the therapeutic or diagnostic evaluation. The StO2 per site and the effect of vasoactive substance on penile and thigh oximetry was recorded. The StO2 recorded for this probe is an average of an approximate volume of 1 cm3 of tissue beneath the probe, well within the corporal body. The raw data was transferred via infrared port to the investigator's computer, where it was then converted into an Excel spreadsheet in which means and standard deviations were calculated for each measured site. Statistical analysis was performed by using the Student's t test and ANOVA with SAS software, JMP 5.1 (Cary, NC).
|
|
Results |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
7), 9% moderate ED (8–14), 27%
mild (15–21), and 16% no ED (22–25).
|
Corporal oxygenation was significantly lower in men with ED than in men
with no ED (Table 2). When
patients were segregated by ED severity, patients with more severe ED (SHIM
7, n = 79) had significantly lower corporal flaccid StO2 than
those with no ED (SHIM > 21, n = 27), though the age was also significantly
higher (Table 3). Sixty-seven
percent of the men with severe ED had undergone RRP, with a mean time from
surgery of 25 months (1–108) and age of 61. Glanular oxygenation was not
affected by ED status or age, by categorical or regression analysis. Age
appeared to have a significant effect on flaccid corporal StO2
after age 60. There appeared to be no consistent trend in men younger than 60
(Table 4).
|
|
|
Administration of PGE-1 intracorporally or intraurethrally resulted in arterialization of corporal and glanular StO2 without increases in thigh measurements. Table 5 contains baseline StO2 measurements for all 171 patients divided into the 5 sites by mean and standard deviation. The pre-PGE1 StO2, postvasoactive StO2, and percent of change for the 64 ED patients are also shown in Table 5. There was a significant mean percentage improvement in StO2 in the ED patients with vasoactive substance in both the corpora and midglans sites. Specifically, there is a 150% (P < .001) improvement in the right corpora, 105% (P < .001) improvement in the left corpora, and 26% (P < .001) improvement in the mid-glans following vasoactive administration. PGE1 had no significant effect on thigh StO2. In men receiving MUSE, the improvement in corporal and glanular StO2 occurred despite the marginal erection. Doses of MUSE used were 125 and 250 µg. The average dose of intracavernosal PGE-1 was less than 10 µg and was always accompanied by a partial or full erection.
|
|
Discussion |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
There was a tremendous improvement in the StO2 of the corpora and the glans with administration of intraurethral or injectable PGE1. As expected, the impotent group was older, had more endothelial risk factors, and included a larger proportion of individuals post-RRP. The StO2 in the flaccid state of the men with ED differed significantly from the non-ED patients Of the group of ED patients, approximately 50% were postprostatectomy. There was no significant difference in StO2 of men with ED after RRP vs non-RRP, despite a marginally significant difference in age (61 vs 56 years, P < .04) and a significant difference in SHIM score (3 vs 13, P < .001). Despite the etiology, there appears to be a chronic state of penile hypoxia seen with severe ED and with advancing age. This chronic hypoxia leads to less NPT with eventual corporal fibrosis and progressive and irreversible ED.
The hemoglobin dissociation curve is useful in understanding penile StO2 measurement. This curve relates StO2 and pO2 in the blood and tissues. The relationship between StO2 and the tissue pO2 is dependent on many factors, but like the hemoglobin dissociation curve is nonlinear. The affinity of hemoglobin (Hb) for oxygen increases as successive molecules of oxygen bind until saturation, at which point the curve plateaus (60 mm Hg). Below 60 mm Hg, small fluctuations in pO2 lead to a significant drop in StO2 and significant hypoxia. P50 is a conventional measure of affinity for oxygen, indicating the pO2 at which Hb is 50% saturated (26.83 mm Hg). In our ED population the flaccid corporal saturation averaged less than 50%. With the loss of NPT, particularly after RRP, the corpora are chronically a profoundly hypoxic microenvironment. The difference between the corporal and glanular saturation probably reflects the different blood supply. Though the thinness of the glanular epithelial layer might be implicated as a reason for increased StO2, the thigh with its much thicker dermis and subcutaneous layer consistently had a higher StO2 than the flaccid corpora.
Application of PGE1 to this group resulted in near arterialization of the corpora. PGE1 raised the StO2 150 percent to 76.58%, which corresponds to a pO2 of 41.8 mm Hg. The increase in corporal StO2 with PGE-1 supports the studies of Montorsi showing the value of postoperative PGE-1 injections in the recovery of erectile function after RRP.
This study serves to provide data on flaccid and erect StO2 levels in men with and without ED. We demonstrate the use of a novel, noninvasive, accurate method of measuring intracavernosal oxygenation both in the flaccid and erect state.
|
Conclusions |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
|
Footnotes |
|---|
|
References |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionConclusionsReferences |
|---|
Fraiman MC, Lepor H, McCullough AR. Changes in penile morphometrics in men with erectile dysfunction after nerve-sparing radical retropubic prostatectomy. Mol Urol. 1999; 3: 109 –115.[Medline]
Karacan I, Salis PJ, Hirshkowitz M, Borreson RE, Narter E, Williams RL. Erectile dysfunction in hypertensive men: sleep-related erections, penile blood flow and musculovascular events. J Urol. 1989; 142: 56 –61.[Medline]
Karacan I, Salis PJ, Ware JC, Dervent B, Williams RL, Scott FB,
Attia SL, Beutler LE. Nocturnal penile tumescence and diagnosis in diabetic
impotence. Am J Psychiatry. 1978; 135: 191
–197.
Kim N, Vardi Y, Padma-Nathan H, Daley J, Goldstein I, Saenz de Tejada I. Oxygen tension regulates the nitric oxide pathway. Physiological role in penile erection. J Clin Invest. 1993; 91: 437 –442.[Medline]
Kim NN, Kim JJ, Hypolite J, Garcia-Diaz JF, Broderick GA, Tornheim K, Daley JT, Levin R, Saenz de Tejada I. Altered contractility of rabbit penile corpus cavernosum smooth muscle by hypoxia. J Urol. 1996;155: 772 –778.[CrossRef][Medline]
Klein LT, Miller MI, Buttyan R, Raffo AJ, Burchard M, Devris G, Cao YC, Olsson C, Shabsigh R. Apoptosis in the rat penis after penile denervation. J Urol. 1997;158: 626 –630.[CrossRef][Medline]
McCullough AR. Prevention and management of erectile dysfunction following radical prostatectomy. Urol Clin North Am. 2001; 28: 613 –627.[CrossRef][Medline]
Padma-Nathan H, McCullough A, Forest C. Erectile dysfunction secondary to nerve-sparing radical retropubic prostatectomy: comparative phosphodiesterase-5 inhibitor efficacy for therapy and novel prevention strategies. Curr Urol Rep. 2004; 5: 467 –471.[Medline]
Schwartz EJ, Wong P, Graydon RJ. Sildenafil preserves intracorporeal smooth muscle after radical retropubic prostatectomy. J Urol. 2004;171: 771 –774.[CrossRef][Medline]
Tamura M, Kawanishi Y, Furukawa A, Numata A, Yusa M, Imagawa A. [Ligation of the crura penis: surgical treatment for venous impotence]. Hinyokika Kiyo. 1990; 36: 127 –130.[Medline]
User HM, Hairston JH, Zelner DJ, McKenna KE, McVary KT. Penile weight and cell subtype specific changes in a post-radical prostatectomy model of erectile dysfunction. J Urol. 2003; 169: 1175 –1179.[CrossRef][Medline]
Xu X, Zhu W, Padival V, Xia M, Cheng X, Bush R, Christenson L, Chan T, Doherty T, Latridis A. Validation of NIRS in measuring tissue hemoglobin concentration and oxygen saturation on ex vivo and isolated limb models. Proc SPIE. 2003; 4955: 369 .[CrossRef]
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
