Download Cavernous oxygen tension in the patients with erectile

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 ˆ 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 ˆ 0.66, P < 0.001) was
statistically signi®cant (Figure 3), and sO2/PSV
(r ˆ 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 ˆ 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.
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