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Evaluation of Vasculogenic Impotence by Monitoring of Cavernous Oxygen Tension
0022-534 7/93/1495-1276$03.00/0 Vol. 149, 1276-1279, May 1993 Printed in U.S.A.
THE JOURNAL OF UROLOGY Copyright© 1993 by AMERICAN UROLOGICAL ASSOCIATION, INC.
EVALUATION OF VASCULOGENIC IMPOTENCE BY MONITORING OF CAVERNOUS OXYGEN TENSION H. H. KNISPEL
AND
R. ANDRESEN
From the Departments of Urology and Radiology, Klinikum Steglitz, Free University Berlin, Germany
ABSTRACT
Color coded duplex sonography, regarded as the gold standard in penile vascular evaluation, does not yield data on cavernous oxygenation itself. In addition to using color coded duplex sonography to measure peak flow velocity in cavernous arteries after injection of 20 µg. prostaglandin El in 34 unselected patients with impotence, we monitored cavernous oxygen tension with an oxygensensitive Eppendorf needle electrode. During flaccidity the mean cavernous oxygen tension of 38 mm. Hg increased to 61 mm. Hg after injection of prostaglandin El. Peak flow shown with color coded duplex sonography and maximal oxygen tension correlated well in 24 men (71%). However, in 10 men (29%) normal peak flow did not result in a cavernous oxygen tension of greater than 65 mm. Hg, so this might have been isolated cavernous perfusion defects. In contrast, there was no case of impaired arterial inflow and high oxygen tension. Monitoring of cavernous oxygen tension allows for characterization of patients with cavernous perfusion deficiency. This new and simple diagnostic method might help to improve diagnosis and followup after penile vascular surgery. However, more data on patients and controls will be required to define normal ranges. KEY WORDS:
impotence, penile erection, oxygen, prostaglandins E, ultrasonography
Penile vascular surgery in impotence currently is based on angiography, duplex sonography and dynamic pharmacocavernosography. Failures in restoring erectile function might be due to inconsistent diagnosis and surgical technique. 1 • 2 In view of the central role of cavernous smooth muscle relaxation in inducing penile erection, the data suggest that vascular impotence might be linked to cavernous malfunction, rather than impaired flow in the cavernous arteries alone. 3 However, flow characteristics in the cavernous arteries, best measured with color coded duplex sonography, 4 • 5 do not indicate oxygenation itself. We identify impaired cavernous perfusion in impotent patients by combining color coded duplex sonography with a new and simple method of monitoring cavernous oxygen tension after injection of prostaglandin EL MATERIALS AND METHODS
After written informed consent, 34 unselected patients with impotence were included in the study. We obtained and examined thorough medical and sexual histories. Laboratory tests consisted of a blood count, urinalysis and measurement of glucose, triglycerides, cholesterol, prolactin and testosterone. All men underwent cavernous drug testing with 20 µg. prostaglandin El and recording of erectile response. Penile arterial evaluation was done by color coded duplex sonography with a 7.5 MHz. transducer (Philips/Quantum, slow-flow package). After cavernous injection of 20 µg. prostaglandin El via a previously described method6 peak flow velocity was measured in both cavernous arteries and all patients underwent dynamic pharmacocavernosography. Cavernous oxygen tension was measured with sterilizable, unbreakable needle probes coated with spring steel (diameter 350 µm., fig. 1) 7 at a polarographic membranized gold microcathode situated within a recess on the ground surface of the probe tip. Before and after insertion in the corpus cavernosum the probes were calibrated in buffered physiological saline that was alternately saturated with air and nitrogen. The probe current values obtained at intervals of 2 to 3 seconds were stored in an attached personal computer, which allowed us to recalibrate calculations. Accepted for publication February 12, 1993.
FIG. 1.
Oxygen tension Eppendorf needle electrode with probe tip
With local anesthesia of the sulcus coronarius we inserted a 22 gauge cannula longitudinally into the corpus cavernosum and obtained a blood sample for blood-gas analysis using a micropipet by slightly squeezing the penis. We then inserted the calibrated probe and took 50 to 80 oxygen tension values with the penis in the flaccid state. The data were processed by the attached personal computer and expressed as a mean. Monitoring of oxygen tension continued after injection of 20 µg. prostaglandin El into the contralateral corpus cavernosum until maximal oxygen tension was achieved. When a steady state had been reached, we took another 50 to 80 values and processed them as described previously. Finally, we took another cavernous blood sample for blood-gas analysis. RESULTS
The presence of neurovascular risk factors was evident in 25 of the 34 men (74%): 10 were smokers (more than 10 cigarettes per day), arterial hypertension was present in 12, 7 had diabetes mellitus, hyperlipidemia was diagnosed in 7 and 4 were "clean" alcohol abusers. After cavernous injection of 20 µg. prostaglandin El, peak flow velocity in the cavernous arteries of the 34 patients was 12 to 61 cm. per second (fig. 2). In 23 men (68%) peak flow velocity exceeded 25 cm. per second. Failure to reach that velocity indicated impaired perfusion in the cavernous arteries. Of 34 men 32 (94%) demonstrated penile tumescence
1276
1277
VASCULOGENIC IMPOTENCE EVALUATED BY CAVERNOUS OXYGEN TENSION mmHg
n 16 14
100 12
10
80
8
60.
6 4
40.
2
0 X<15
25iX<35
15
351X<45
45
x,ss
20.
Hcm/s
FIG. 2. Peak flow velocity in cavernous arteries of 34 impotent patients after intracavernous injection of 20 µg. prostaglandin El.
p02
after PGE1
flaccid state
FIG. 4. Comparative oxygen tension (p0 2 ) values taken by electrode and blood gas analysis before and after intracavernous injection of 20 µg. prostaglandin El (PGEl).
"'""½i 11!1! !II 1!11 ?I !ill
.../ -
/~
56 1!11
:Ii
r"'
"l.
.,I
i!D fl!
-
ij
II
i!
~
5
min
t
Fm. 3. Monitoring of cavernous oxygen tension (pO,) in patient with full erectile response to prostaglandin El and maximal peak flow velocity in cavernous arteries of 52 cm. per second.
after injection of prostaglandin El but only 20 (59%) achieved erection sufficient for intercourse. During flaccidity the mean cavernous oxygen tension was 38 mm. Hg (range 28 to 47). Starting 35 to 60 seconds after injection prostaglandin El induced a continuous increase in oxygen tension up to a mean steady state of 61 mm. Hg (range 48 to 89, fig. 3), which was reached after a maximum of 8 minutes 30 seconds. In addition to measuring oxygen with the oxygen probe, sampling of cavernous blood for blood-gas analysis was successful in the flaccid state in 16 men and in the erect state in 24 men. Maximal differences between correspondingly measured oxygen tension values were 12.4% in flaccidity and 8. 7% after prostaglandin El. Comparative values before and after injection of prostaglandin El are given in figure 4. There was no statistically significant difference. Reproducibility of oxygen tension measurements taken with the needle electrode as well as blood-gas analysis have been tested in 5 patients and demonstratr :! only minimal differences intra-individually compared to inter-individually. According to the distribution of oxygen tension values (fig. 5) we arbitrarily set the cutoff value to characterize impaired cavernous perfusion at 65 mm. Hg. Cavernous perfusion was regarded as normal in 13 of 34 men (38%) and pathological in 21 (62% ). Correlation with peak flow in cavernous arteries after injection ofprostaglandin El as measured by color coded duplex sonography resulted in 3 groups (see table). In no patient did low flow appear with normal cavernous oxygen tension (group 4). Significant venous leakage, defined by maintenance flow rates exceeding 30 ml. per minute after injection of 20 µg. prostaglandin El, was shown in 12 of the 34 patients (35%). Assignment to groups 1 to 4 did not reveal any significant difference in leakage flow (see table). Further computerized processing of the data did not yield any correlation between erectile response after injection of prostaglandin El and max-
X<45
45iX<55
55,X<65
65,X<75
75,X<85
>85
•[mmHgJ
FIG. 5. Maximum cavernous oxygen tension in 34 impotent patients after intracavernous injection of 20 µg. prostaglandin El.
Classification of 34 impotent patients according to results of oxygen tension monitorings and color coded duplex sonography of cavernous arteries after intracavernous injection of 20 µg. prostaglandin El Group 1 2 3 4
Oxygen Tension (mm.Hg) More than 65 Less than 65 Less than 65 More than 65
Peak Flow Velocity (cm./sec.) More than 25 Less than 25 More than 25 Less than 25
No. Pts. (%)
13 (38.2) 11 (32.4) 10 (29.4) 0
No. With Leakage 5 4
3 0
imal oxygen tension levels or the slope of increase in oxygen tension. DISCUSSION
The high prevalence of vascular risk factors in our patients might indicate a high rate of impaired penile perfusion as demonstrated in previous series. 6 • 8 Peak flow velocity in cavernous arteries measured with color coded duplex sonography after injection of a vasoactive drug is currently regarded as the best measure of penile perfusion capacity. 4 • 5 Therefore, we used color coded duplex sonography as a reference method to define arteriogenic impotence in patients who did not exceed the cutoff line of 25 cm. per second in peak flow velocity. 9 • 10 Although recent data have cast some doubt on that cutoff value, there is no better parameter available yet. 5• 6 However, vascular disease might not be limited to supplying
1278
KNISPEL AND ANDRESEN
arteries. Radioisotopic methods, as first described by Shirai et al,11 avoid that limitation by including evaluation of a cavernous body as a single vascular unit. The techniques used, however, were too elaborate for routine application in diagnosis of impotence. 12• 13 Nevertheless, from a theoretical viewpoint, direct measurement of cavernous oxygen tension must be regarded as the best source of information on microperfusion. The development of unbreakable, small caliber oxygen-sensitive probes has advanced the clinical application of the method.7 In their pioneering work, Aoki et al used a polarographic technique to study penile hemodynamics in healthy men, which allowed them to estimate alterations of oxygen tension.14 Our investigation was done with the Eppendorf oxygen tension Histograph, which is more clinically adapted and expresses oxygen tension in mm. Hg. A high correlation between the values derived with the probe and from blood-gas analysis demonstrates the high validity of the method. It allowed for rapid and simple monitoring of oxygen tension before and after injection of prostaglandin El. Our data obtained during flaccidity confirm those of other investigators who compared cavernous oxygen tension with venous blood oxygen tension.14- 16 Flaccidity is associated with minimal flow rates in the cavernous arteries.5 Aoki et al used visual sexual stimulation and described a sudden increase in cavernous oxygen tension at the onset of penile tumescence.14 After injection of prostaglandin El in our patients, however, we found a delay of 35 to 60 seconds in the increase in oxygen tension, which might be the period between onset of smooth muscle relaxation and alterations of cavernous microcirculation. Our monitoring included oxygen tension values from penile flaccidity to steady tumescence after injection ofprostaglandin El and resulted in almost uniform curves, such as in figure 3, which were not significantly influenced by the presence of venous leakage. Vardi et al studied cavernous oxygen tension after injection of papaverine plus phentolamine by blood-gas analysis, reaching values of 80 to 105 mm. Hg. 16 The difference in oxygen tension levels to the presented series might be due to the vasoactive drugs used. While prostaglandin El can be dissolved in physiological saline, injection of papaverine requiring a pH of 4.0 will have significant influence on cavernous pH and, consequently, blood-gas analysis.17 A low correlation between erectile response to prostaglandin El and maximal cavernous oxygen tension might indicate that prostaglandin El influences arterial inflow, including cavernous perfusion of sinusoids, independently from venous outflow. Definition of normal values of cavernous oxygen tension monitoring requires evaluation of healthy controls. Invasiveness of the method, however, did allow first studies only in patients suffering from impotence due to ethical reasons. Therefore, we assigned patients arbitrarily, according to the distribution of oxygen tension levels at 65 mm. Hg, to low and high groups and compared them to findings in color coded duplex sonography. Assignment of patients to different groups according to the results of color coded duplex sonography and oxygen tension monitoring demonstrated results in the same direction in 71 % of the men (groups 1 and 3, see table) . However, 29 % of the patients had impaired cavernous perfusion despite normal arterial flow velocity, which might lead to the conclusion that impaired cavernous oxygenation cannot be ruled out by color coded duplex sonography alone and that common revascularization procedures could be useless in these patients. However, one may speculate about the role of a high anxiety level influencing cavernous perfusion in these patients by high epinephrine levels. More elaborate studies measuring oxygen tension simultaneously at different sites of the corpus cavernosum might provide more data on that question. No patient with low flow in the cavernous arteries had normal cavernous perfusion, which supports theories of primarily endothelium-mediated
vascular impairment as a main cause of erectile dysfunction.3 Vascular disorders in cavernous arteries measured by color coded duplex sonography might be a sign of progressive disease. Influence of oxygen tension on contractility of vascular smooth muscle, as demonstrated in several studies, 18 might have an important role in penile erection, since smooth muscle relaxation is regarded as the main event in erection. Nitric oxide has been shown to be the chief producer of relaxation of penile smooth muscle, 19 so the importance of cavernous oxygen tension is evident. The half-life of nitric oxide depends mainly on concentrations of molecular oxygen, superoxide anions and hydroxyl radicals, which are directly proportional to tissue oxygen tension. 20 In conclusion, monitoring of cavernous oxygen tension after injection of prostaglandin El allows for identification of impaired cavernous perfusion in impotent patients. It also contributes knowledge about the role of nitric oxide in relaxation of cavernous smooth muscle. However, a greater number of control subjects will be required to define normal ranges and studies on isolated cavernous smooth muscle will have to prove the physiological role of oxygen tension in penile erection. Prof. Dr. K. Reinhardt, Department of Anesthesiology and Intensive Care, Free University Berlin, Klinikum Steglitz, provided technical equipment. REFERENCES 1. Hauri, D.: A new operative technique in vasculogenic erectile impotence. World J . Urol., 4: 237, 1986. 2. Sohn, M. , Sikora, R. , Bohndorf, K. and Deutz, F.-J.: Selective microsurgery in arteriogenic erectile failure. World J . Urol., 8: 104, 1990. 3. Saenz de Tejada, I., Goldstein, I., Azadzoi, K. , Krane, R. J. and Cohen, R. A.: Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence. New Engl. J . Med., 320: 1025, 1989. 4. Lopez, J. A., Espeland, M.A. and Jarow, J.P.: Interpretation and quantification of penile blood flow studies using duplex ultrasonography. J . Urol., 146: 1271, 1991. 5. Meuleman, E. J. H., Bemelmans, B. L. H., van Asten, W. N . J.C., Doesburg, W. H., Skotnicki, S. H. and Debruyne, F. M. J.: Assessment of penile blood flow by duplex ultrasonography in 44 men with normal erectile potency in different phases of erection. J . Urol., 147: 51, 1992. 6. Knispel, H. H. and Andresen, R.: Color-coded duplex sonography in impotence: significance of different flow parameters in patients and controls. Eur. Urol., 21: 22, 1992. 7. Fleckenstein, W., Weiss, C., Heinrich, R. , Schomerus, H. and Kersting, T.: A new method for the bed-side recording of tissue pOrhistograms. Verh. Dtsch. Ges. Inn. Med., 90: 439, 1984. 8. Shabsigh, R. , Fishman, I. J ., Schum, C. and Dunn, J . K.: Cigarette smoking and other vascular risk factors in vasculogenic impotence. Urology, 38: 227, 1991. 9. Lue, T. F., Hricak, H., Marich, K. W. and Tanagho, E. A.: Vasculogenic impotence evaluated by high-resolution ultrasonography and pulsed Doppler spectrum analysis. Radiology, 155: 777, 1985. 10. Benson, C. B. and Vickers, M . A.: Sexual impotence caused by vascular disease: diagnosis with duplex sonography. AJR, 153: 1149, 1989. 11. Shirai, M., Ishii, N., Mitsukawa, S., Matsuda, S. and Nakamura, N.: Hemodynamic mechanism of erection in the human penis. Arch. Androl., 1: 345, 1978. 12. Kim, S. C., Kim, K. B. and Oh, C. H.: Diagnostic value of the radioisotope erection penogram for vasculogenic impotence. J. Urol., 144: 888, 1990. 13. Esen, A., Kitapci, M., Ergen, A., Erbas, B., Remzi, D. and Bekdik, C.: Dual radioisotopic study: a technique for the evaluation of vasculogenic impotence. J . Urol., 147: 42, 1992. 14. Aoki, H., Tkagane, H., Banya, Y., Fujioka, T ., Seo, K. , Kubo, T. and Ohhori, T.: Human penile hemodynamics studied by a polarographic method. J . Urol., 13 5: 872, 1986. 15. Juenemann, K. P ., Lue, T . F., Abozeid, M., Hellstrom, W. J . and
VASCULOGENIC IMPOTENCE EVALUATED BY CAVERNOUS OXYGEN TENSION
Tanagho, E. A.: Biood gas analysis in drug-induced penile erection. Urol. Int., 41: 207, 1986. 16. Vardi, Y., Lidgi, S. and Levin, D.R.: Intracavernous p02 response to vasoactive drugs as an indicator of corporal vascular dysfunction. Int. J. Impotence Res., suppl. 2, 2: 242, 1990. 17. Seidmon, E. J. and Samaha, A. M., Jr.: The pH analysis of papaverine-phentolamine and prostaglandin El for pharmacologic erection. J. Urol., 141: 1458, 1989. 18. Grote, J., Siegel, G., Zimmer, K. and Adler, A.: The influence of
1279
oxygen tension of membrane potential of canine carotid artery smooth muscle. Adv. Exp. Med. Biol., 222: 481, 1988. 19. Knispel, H. H., Goessl, C. and Beckmann, R.: Nitric oxide mediates relaxation in rabbit and human corpus cavernosum smooth muscle. Urol. Res., 20: 253, 1992. 20. Kelm, M., Feelisch, M., Deu/1,en, A., Schrader, J. and Strauer, B. E.: The role of nitric oxide in the control of coronary vascular tone in relation to partial oxygen pressure, perfusion pressure, and flow. J. Cardiovasc. Pharmacol., suppl. 3., 17: 895, 1991.
THE JOURNAL OF UROLOGY Copyright© 1993 by AMERICAN UROLOGICAL ASSOCIATION, INC.
EVALUATION OF VASCULOGENIC IMPOTENCE BY MONITORING OF CAVERNOUS OXYGEN TENSION H. H. KNISPEL
AND
R. ANDRESEN
From the Departments of Urology and Radiology, Klinikum Steglitz, Free University Berlin, Germany
ABSTRACT
Color coded duplex sonography, regarded as the gold standard in penile vascular evaluation, does not yield data on cavernous oxygenation itself. In addition to using color coded duplex sonography to measure peak flow velocity in cavernous arteries after injection of 20 µg. prostaglandin El in 34 unselected patients with impotence, we monitored cavernous oxygen tension with an oxygensensitive Eppendorf needle electrode. During flaccidity the mean cavernous oxygen tension of 38 mm. Hg increased to 61 mm. Hg after injection of prostaglandin El. Peak flow shown with color coded duplex sonography and maximal oxygen tension correlated well in 24 men (71%). However, in 10 men (29%) normal peak flow did not result in a cavernous oxygen tension of greater than 65 mm. Hg, so this might have been isolated cavernous perfusion defects. In contrast, there was no case of impaired arterial inflow and high oxygen tension. Monitoring of cavernous oxygen tension allows for characterization of patients with cavernous perfusion deficiency. This new and simple diagnostic method might help to improve diagnosis and followup after penile vascular surgery. However, more data on patients and controls will be required to define normal ranges. KEY WORDS:
impotence, penile erection, oxygen, prostaglandins E, ultrasonography
Penile vascular surgery in impotence currently is based on angiography, duplex sonography and dynamic pharmacocavernosography. Failures in restoring erectile function might be due to inconsistent diagnosis and surgical technique. 1 • 2 In view of the central role of cavernous smooth muscle relaxation in inducing penile erection, the data suggest that vascular impotence might be linked to cavernous malfunction, rather than impaired flow in the cavernous arteries alone. 3 However, flow characteristics in the cavernous arteries, best measured with color coded duplex sonography, 4 • 5 do not indicate oxygenation itself. We identify impaired cavernous perfusion in impotent patients by combining color coded duplex sonography with a new and simple method of monitoring cavernous oxygen tension after injection of prostaglandin EL MATERIALS AND METHODS
After written informed consent, 34 unselected patients with impotence were included in the study. We obtained and examined thorough medical and sexual histories. Laboratory tests consisted of a blood count, urinalysis and measurement of glucose, triglycerides, cholesterol, prolactin and testosterone. All men underwent cavernous drug testing with 20 µg. prostaglandin El and recording of erectile response. Penile arterial evaluation was done by color coded duplex sonography with a 7.5 MHz. transducer (Philips/Quantum, slow-flow package). After cavernous injection of 20 µg. prostaglandin El via a previously described method6 peak flow velocity was measured in both cavernous arteries and all patients underwent dynamic pharmacocavernosography. Cavernous oxygen tension was measured with sterilizable, unbreakable needle probes coated with spring steel (diameter 350 µm., fig. 1) 7 at a polarographic membranized gold microcathode situated within a recess on the ground surface of the probe tip. Before and after insertion in the corpus cavernosum the probes were calibrated in buffered physiological saline that was alternately saturated with air and nitrogen. The probe current values obtained at intervals of 2 to 3 seconds were stored in an attached personal computer, which allowed us to recalibrate calculations. Accepted for publication February 12, 1993.
FIG. 1.
Oxygen tension Eppendorf needle electrode with probe tip
With local anesthesia of the sulcus coronarius we inserted a 22 gauge cannula longitudinally into the corpus cavernosum and obtained a blood sample for blood-gas analysis using a micropipet by slightly squeezing the penis. We then inserted the calibrated probe and took 50 to 80 oxygen tension values with the penis in the flaccid state. The data were processed by the attached personal computer and expressed as a mean. Monitoring of oxygen tension continued after injection of 20 µg. prostaglandin El into the contralateral corpus cavernosum until maximal oxygen tension was achieved. When a steady state had been reached, we took another 50 to 80 values and processed them as described previously. Finally, we took another cavernous blood sample for blood-gas analysis. RESULTS
The presence of neurovascular risk factors was evident in 25 of the 34 men (74%): 10 were smokers (more than 10 cigarettes per day), arterial hypertension was present in 12, 7 had diabetes mellitus, hyperlipidemia was diagnosed in 7 and 4 were "clean" alcohol abusers. After cavernous injection of 20 µg. prostaglandin El, peak flow velocity in the cavernous arteries of the 34 patients was 12 to 61 cm. per second (fig. 2). In 23 men (68%) peak flow velocity exceeded 25 cm. per second. Failure to reach that velocity indicated impaired perfusion in the cavernous arteries. Of 34 men 32 (94%) demonstrated penile tumescence
1276
1277
VASCULOGENIC IMPOTENCE EVALUATED BY CAVERNOUS OXYGEN TENSION mmHg
n 16 14
100 12
10
80
8
60.
6 4
40.
2
0 X<15
25iX<35
15
351X<45
45
x,ss
20.
Hcm/s
FIG. 2. Peak flow velocity in cavernous arteries of 34 impotent patients after intracavernous injection of 20 µg. prostaglandin El.
p02
after PGE1
flaccid state
FIG. 4. Comparative oxygen tension (p0 2 ) values taken by electrode and blood gas analysis before and after intracavernous injection of 20 µg. prostaglandin El (PGEl).
"'""½i 11!1! !II 1!11 ?I !ill
.../ -
/~
56 1!11
:Ii
r"'
"l.
.,I
i!D fl!
-
ij
II
i!
~
5
min
t
Fm. 3. Monitoring of cavernous oxygen tension (pO,) in patient with full erectile response to prostaglandin El and maximal peak flow velocity in cavernous arteries of 52 cm. per second.
after injection of prostaglandin El but only 20 (59%) achieved erection sufficient for intercourse. During flaccidity the mean cavernous oxygen tension was 38 mm. Hg (range 28 to 47). Starting 35 to 60 seconds after injection prostaglandin El induced a continuous increase in oxygen tension up to a mean steady state of 61 mm. Hg (range 48 to 89, fig. 3), which was reached after a maximum of 8 minutes 30 seconds. In addition to measuring oxygen with the oxygen probe, sampling of cavernous blood for blood-gas analysis was successful in the flaccid state in 16 men and in the erect state in 24 men. Maximal differences between correspondingly measured oxygen tension values were 12.4% in flaccidity and 8. 7% after prostaglandin El. Comparative values before and after injection of prostaglandin El are given in figure 4. There was no statistically significant difference. Reproducibility of oxygen tension measurements taken with the needle electrode as well as blood-gas analysis have been tested in 5 patients and demonstratr :! only minimal differences intra-individually compared to inter-individually. According to the distribution of oxygen tension values (fig. 5) we arbitrarily set the cutoff value to characterize impaired cavernous perfusion at 65 mm. Hg. Cavernous perfusion was regarded as normal in 13 of 34 men (38%) and pathological in 21 (62% ). Correlation with peak flow in cavernous arteries after injection ofprostaglandin El as measured by color coded duplex sonography resulted in 3 groups (see table). In no patient did low flow appear with normal cavernous oxygen tension (group 4). Significant venous leakage, defined by maintenance flow rates exceeding 30 ml. per minute after injection of 20 µg. prostaglandin El, was shown in 12 of the 34 patients (35%). Assignment to groups 1 to 4 did not reveal any significant difference in leakage flow (see table). Further computerized processing of the data did not yield any correlation between erectile response after injection of prostaglandin El and max-
X<45
45iX<55
55,X<65
65,X<75
75,X<85
>85
•[mmHgJ
FIG. 5. Maximum cavernous oxygen tension in 34 impotent patients after intracavernous injection of 20 µg. prostaglandin El.
Classification of 34 impotent patients according to results of oxygen tension monitorings and color coded duplex sonography of cavernous arteries after intracavernous injection of 20 µg. prostaglandin El Group 1 2 3 4
Oxygen Tension (mm.Hg) More than 65 Less than 65 Less than 65 More than 65
Peak Flow Velocity (cm./sec.) More than 25 Less than 25 More than 25 Less than 25
No. Pts. (%)
13 (38.2) 11 (32.4) 10 (29.4) 0
No. With Leakage 5 4
3 0
imal oxygen tension levels or the slope of increase in oxygen tension. DISCUSSION
The high prevalence of vascular risk factors in our patients might indicate a high rate of impaired penile perfusion as demonstrated in previous series. 6 • 8 Peak flow velocity in cavernous arteries measured with color coded duplex sonography after injection of a vasoactive drug is currently regarded as the best measure of penile perfusion capacity. 4 • 5 Therefore, we used color coded duplex sonography as a reference method to define arteriogenic impotence in patients who did not exceed the cutoff line of 25 cm. per second in peak flow velocity. 9 • 10 Although recent data have cast some doubt on that cutoff value, there is no better parameter available yet. 5• 6 However, vascular disease might not be limited to supplying
1278
KNISPEL AND ANDRESEN
arteries. Radioisotopic methods, as first described by Shirai et al,11 avoid that limitation by including evaluation of a cavernous body as a single vascular unit. The techniques used, however, were too elaborate for routine application in diagnosis of impotence. 12• 13 Nevertheless, from a theoretical viewpoint, direct measurement of cavernous oxygen tension must be regarded as the best source of information on microperfusion. The development of unbreakable, small caliber oxygen-sensitive probes has advanced the clinical application of the method.7 In their pioneering work, Aoki et al used a polarographic technique to study penile hemodynamics in healthy men, which allowed them to estimate alterations of oxygen tension.14 Our investigation was done with the Eppendorf oxygen tension Histograph, which is more clinically adapted and expresses oxygen tension in mm. Hg. A high correlation between the values derived with the probe and from blood-gas analysis demonstrates the high validity of the method. It allowed for rapid and simple monitoring of oxygen tension before and after injection of prostaglandin El. Our data obtained during flaccidity confirm those of other investigators who compared cavernous oxygen tension with venous blood oxygen tension.14- 16 Flaccidity is associated with minimal flow rates in the cavernous arteries.5 Aoki et al used visual sexual stimulation and described a sudden increase in cavernous oxygen tension at the onset of penile tumescence.14 After injection of prostaglandin El in our patients, however, we found a delay of 35 to 60 seconds in the increase in oxygen tension, which might be the period between onset of smooth muscle relaxation and alterations of cavernous microcirculation. Our monitoring included oxygen tension values from penile flaccidity to steady tumescence after injection ofprostaglandin El and resulted in almost uniform curves, such as in figure 3, which were not significantly influenced by the presence of venous leakage. Vardi et al studied cavernous oxygen tension after injection of papaverine plus phentolamine by blood-gas analysis, reaching values of 80 to 105 mm. Hg. 16 The difference in oxygen tension levels to the presented series might be due to the vasoactive drugs used. While prostaglandin El can be dissolved in physiological saline, injection of papaverine requiring a pH of 4.0 will have significant influence on cavernous pH and, consequently, blood-gas analysis.17 A low correlation between erectile response to prostaglandin El and maximal cavernous oxygen tension might indicate that prostaglandin El influences arterial inflow, including cavernous perfusion of sinusoids, independently from venous outflow. Definition of normal values of cavernous oxygen tension monitoring requires evaluation of healthy controls. Invasiveness of the method, however, did allow first studies only in patients suffering from impotence due to ethical reasons. Therefore, we assigned patients arbitrarily, according to the distribution of oxygen tension levels at 65 mm. Hg, to low and high groups and compared them to findings in color coded duplex sonography. Assignment of patients to different groups according to the results of color coded duplex sonography and oxygen tension monitoring demonstrated results in the same direction in 71 % of the men (groups 1 and 3, see table) . However, 29 % of the patients had impaired cavernous perfusion despite normal arterial flow velocity, which might lead to the conclusion that impaired cavernous oxygenation cannot be ruled out by color coded duplex sonography alone and that common revascularization procedures could be useless in these patients. However, one may speculate about the role of a high anxiety level influencing cavernous perfusion in these patients by high epinephrine levels. More elaborate studies measuring oxygen tension simultaneously at different sites of the corpus cavernosum might provide more data on that question. No patient with low flow in the cavernous arteries had normal cavernous perfusion, which supports theories of primarily endothelium-mediated
vascular impairment as a main cause of erectile dysfunction.3 Vascular disorders in cavernous arteries measured by color coded duplex sonography might be a sign of progressive disease. Influence of oxygen tension on contractility of vascular smooth muscle, as demonstrated in several studies, 18 might have an important role in penile erection, since smooth muscle relaxation is regarded as the main event in erection. Nitric oxide has been shown to be the chief producer of relaxation of penile smooth muscle, 19 so the importance of cavernous oxygen tension is evident. The half-life of nitric oxide depends mainly on concentrations of molecular oxygen, superoxide anions and hydroxyl radicals, which are directly proportional to tissue oxygen tension. 20 In conclusion, monitoring of cavernous oxygen tension after injection of prostaglandin El allows for identification of impaired cavernous perfusion in impotent patients. It also contributes knowledge about the role of nitric oxide in relaxation of cavernous smooth muscle. However, a greater number of control subjects will be required to define normal ranges and studies on isolated cavernous smooth muscle will have to prove the physiological role of oxygen tension in penile erection. Prof. Dr. K. Reinhardt, Department of Anesthesiology and Intensive Care, Free University Berlin, Klinikum Steglitz, provided technical equipment. REFERENCES 1. Hauri, D.: A new operative technique in vasculogenic erectile impotence. World J . Urol., 4: 237, 1986. 2. Sohn, M. , Sikora, R. , Bohndorf, K. and Deutz, F.-J.: Selective microsurgery in arteriogenic erectile failure. World J . Urol., 8: 104, 1990. 3. Saenz de Tejada, I., Goldstein, I., Azadzoi, K. , Krane, R. J. and Cohen, R. A.: Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence. New Engl. J . Med., 320: 1025, 1989. 4. Lopez, J. A., Espeland, M.A. and Jarow, J.P.: Interpretation and quantification of penile blood flow studies using duplex ultrasonography. J . Urol., 146: 1271, 1991. 5. Meuleman, E. J. H., Bemelmans, B. L. H., van Asten, W. N . J.C., Doesburg, W. H., Skotnicki, S. H. and Debruyne, F. M. J.: Assessment of penile blood flow by duplex ultrasonography in 44 men with normal erectile potency in different phases of erection. J . Urol., 147: 51, 1992. 6. Knispel, H. H. and Andresen, R.: Color-coded duplex sonography in impotence: significance of different flow parameters in patients and controls. Eur. Urol., 21: 22, 1992. 7. Fleckenstein, W., Weiss, C., Heinrich, R. , Schomerus, H. and Kersting, T.: A new method for the bed-side recording of tissue pOrhistograms. Verh. Dtsch. Ges. Inn. Med., 90: 439, 1984. 8. Shabsigh, R. , Fishman, I. J ., Schum, C. and Dunn, J . K.: Cigarette smoking and other vascular risk factors in vasculogenic impotence. Urology, 38: 227, 1991. 9. Lue, T. F., Hricak, H., Marich, K. W. and Tanagho, E. A.: Vasculogenic impotence evaluated by high-resolution ultrasonography and pulsed Doppler spectrum analysis. Radiology, 155: 777, 1985. 10. Benson, C. B. and Vickers, M . A.: Sexual impotence caused by vascular disease: diagnosis with duplex sonography. AJR, 153: 1149, 1989. 11. Shirai, M., Ishii, N., Mitsukawa, S., Matsuda, S. and Nakamura, N.: Hemodynamic mechanism of erection in the human penis. Arch. Androl., 1: 345, 1978. 12. Kim, S. C., Kim, K. B. and Oh, C. H.: Diagnostic value of the radioisotope erection penogram for vasculogenic impotence. J. Urol., 144: 888, 1990. 13. Esen, A., Kitapci, M., Ergen, A., Erbas, B., Remzi, D. and Bekdik, C.: Dual radioisotopic study: a technique for the evaluation of vasculogenic impotence. J . Urol., 147: 42, 1992. 14. Aoki, H., Tkagane, H., Banya, Y., Fujioka, T ., Seo, K. , Kubo, T. and Ohhori, T.: Human penile hemodynamics studied by a polarographic method. J . Urol., 13 5: 872, 1986. 15. Juenemann, K. P ., Lue, T . F., Abozeid, M., Hellstrom, W. J . and
VASCULOGENIC IMPOTENCE EVALUATED BY CAVERNOUS OXYGEN TENSION
Tanagho, E. A.: Biood gas analysis in drug-induced penile erection. Urol. Int., 41: 207, 1986. 16. Vardi, Y., Lidgi, S. and Levin, D.R.: Intracavernous p02 response to vasoactive drugs as an indicator of corporal vascular dysfunction. Int. J. Impotence Res., suppl. 2, 2: 242, 1990. 17. Seidmon, E. J. and Samaha, A. M., Jr.: The pH analysis of papaverine-phentolamine and prostaglandin El for pharmacologic erection. J. Urol., 141: 1458, 1989. 18. Grote, J., Siegel, G., Zimmer, K. and Adler, A.: The influence of
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oxygen tension of membrane potential of canine carotid artery smooth muscle. Adv. Exp. Med. Biol., 222: 481, 1988. 19. Knispel, H. H., Goessl, C. and Beckmann, R.: Nitric oxide mediates relaxation in rabbit and human corpus cavernosum smooth muscle. Urol. Res., 20: 253, 1992. 20. Kelm, M., Feelisch, M., Deu/1,en, A., Schrader, J. and Strauer, B. E.: The role of nitric oxide in the control of coronary vascular tone in relation to partial oxygen pressure, perfusion pressure, and flow. J. Cardiovasc. Pharmacol., suppl. 3., 17: 895, 1991.