C Eckhard

Christian G. Stief

CJ Carati

Emil A. Tanagho

FR Domer

Francois Benard

G Brindley

I Nadelhalft

JH Semans

JN Langley

JT Clark

LD Dorr

MB Siroky

NO Sjöstrand

Ruud J. L. H. Bosch

Sherif R. Aboseif

TF Lue

TJ Lue

VE Henderson

W Diederichs

WC Groat de

WD Steers

WG Dail

English

Crossref

Stief, Christian Georg

Bénard, Francois

Bosch, Ruud J. L. H.

Aboseif, Sherif R.

Tanagho, Emil A.

Open Access LMU ( Ludwig-Maximilians-Univ. München)

World J Urol (1990) 8:233-236 Free paper ~alof 1' 1 Urology World Journal of 9 Springer-Verlag 1990 The rabbit as a model for neurourologic studies of the lower genitourinary tract* Chr ist ian G. Stief**, Francois  Benard,  Ruud J. L. H. Bosch, Sheri f  R. Aboseif ,  and Emi l  A. Tanagho Department ofUrology, University of California, School of Medicine, San Francisco, CA 94143, USA Summary. We evaluated the rabbit as an animal model for the elucidation of the neurophysiology of erection, ejaculation, and bladder function. In 24 rabbits, stimula- t ion of the hypogastric nerves resulted in penile tumes- cence and contraction of the seminal vesicles and vasa deferentia. St imulat ion of the sympathetic trunks in- duced contraction of the penis, seminal vesicles, and vasa deferentia. Cavernous nerve st imulation induced penile erection with a mean intracavernous pressure of 113 cm H20. Pelvic nerve st imulat ion elicited bladder contrac- tion, but the intraluminal  pressure was low (mean, 9.6 cm H20 ) in comparison with that in other species. Our re- suits indicate that the rabbit may be an appropriate, rela- tively inexpensive, and readily available model for the study of ejaculatory and erectile systems in man. Howev- er, because of anatomic variations, the rabbit bladder ap- pears to be unsuitable for comparative studies in humans. Eckhard [8] first described the application of modern electrophysiologic methods to the penile erectile system of dogs in his classic article of 1863. After dissection, so- matic and autonomic nerves were stimulated and the erectile response was recorded. The same author reported similar experiments in the rabbit 13 years later [9]. Since then, similar neurourologic experiments have been de- scribed in dogs [2, 7, 11, 12, 17], monkeys [14], cats [6, 10, 15, 16], rabbits [18-20],  and rats [3, 4, 21]. An imal  studies are necessary for an understanding of the neurophysiology of the lower genitourinary tract and for assessment of the effect of different ypes of treat- ment. In recent years, ethical and f inancial considerations have reduced the number  of such studies. The rabbit is similar to the rat in cost and availability, but  its greater * This work was supported by grants from the Deutsche Forschungsge- meinschaft (DFG Sti 96/1 und Sti 96/2-1). ** To whom correspondence should be addressed at: Klinik ftir Urolo- gie, Medizinische Hochschule, Konstanty-Gutschow-Strasse 8, W-3000 Hannover 1, Federal Republic of Germany size offers more ease in dissection and in the recording of biologic effects. We undertook this study to evaluate the rabbit as a possible animal model for the study of the neurophysiology of the lower genitourinary tract. Materials and methods A total of 24 white New Zealand rabbits weighing 2.8 - 3.5 kg were used. After they had been given adequate anesthesia with i.p. pentobarbital (40 mg/kg), the rabbits were placed in a supine position a heating pad. Anesthesia w s maintained with 6.5mg i.v. bolus injections of pen- tobarbital as needed, and the rabbits received warm saline i.v. (2 ml/kg-~/h- 1). The animals breathed spontaneously. Systemic blood pressure was monitored through a 22-gauge angiocatheter in the l ft femoral artery. The abdomen was opened by a midline incision. The rectum was double-ligated and severed, and the mesentery of the proximal rectum and distal colon was di sected up to the inferior mesenteric artery. The distal colon was then placed in the upper abdomen. Hypogastric nerves, sympathetic trunks at the level of L6-S 1, pelvic nerves (distal to the branching of the cavernous nerve), and cavernous nerves w re dissected. Custom-made electrodes (coated platinum-iridium wires and medical quality silastic) were placed around these structures (Fig. 1). Stimula- tion parameters were: 1-4V, 20 Hz frequency, 1 ms pulse width, and 30-s duration. The abdomen was filled with paraffin oil at 37 ~ Addi- tional heat was provided with a heating lamp. Three sets of xperiments were done. Neurophysiology of the ejaculator), system In eight rabbits, a 21-gauge needle was inserted into a seminal vesicle for pressure monitoring. A 25-gauge needle was plac d into one of the vasa deferentia and then connected to a T-tube for continuous perfusion of warm saline (Harvard Apparatus; perfusion rate 0.068 ml/min) and simultaneous pressure recording (Fig. 2).Bilateral sympathetic trunks, hypogastric nerves, andcavernous nerves were independently stimulat- ed and the response of the vas deferens and seminal vesicle was record- ed. If the seminal vesicle contracted, the expulsed volume was replac d with warm saline. The first ejaculate was evaluated for the presence of sperm by optic microscopy (X 200). Simultaneous stimulations of the cavernous nerves and hypogastric nerves were also done. Neurophysiology of the erectile system The cavernous bodies were freed from the penile skin in e ght rabbits. A 21-gauge needle wasinserted into one cavernous body for pressure re- 234 ~ trunk ~ogast  ric trunk ~ Cavernous nerve J Urogenital artery Fig. 1. Custom-made lectrodes are placed around both sympathetic trunks, the hypogastric nerves, the left pelvic nerve, and the left cavern- ous nerve were done either alone or simultaneously with stimulation of the hypogastric nerves or sympathetic trunks. All catheters and fluid-filled lines were connected to a Statham (model 23 BC) transducer for pressure recording (Grass Polygraph mod- el 7). All stimulations or stimulation combinations were repeated three times in each rabbit and the results are expressed as the mean of these findings. Statistical analysis was done using Student's t-test. Results Neurophysiology of the ejaculatory system Baseline pressure within the seminal vesicles was 2 -7  (mean 4) cm H20. Stimulation of the hypogastric nerves induced contraction of the seminal vesicles in all rabbits, with an intraluminal pressure of 23 -37  (mean 28) cm HzO (Fig. 3A). This contraction was accompanied by emission of a white, sperm-containing fluid. The same re- sponse was observed after both sympathetic combined hypogastric and sympathetic stimulation. Stimulation of the cavernous nerve alone did not influence the in- traluminal pressure. However, when the cavernous nerve was stimulated before and/or during seminal vesicle con- traction, the intraluminal peak pressure was reduced by a mean of 7 cm H20 (Fig. 3 B). During perfusion, the intraluminal pressure of the vas deferens was 14-23 (mean 20) cm H20. Spontaneous contractions with an interval of 15-45 s between each wave and a mean pressure increase of 8 cm H20 were re- corded. Stimulation of the hypogastric nerves induced an intraluminal pressure increase of 8 -11  (mean 9.3) cm H20, and stimulation of the sympathetic trunks induced a mean pressure increase of 8 cm H20. Combined stimu- Fig. 2. Intraluminal pressure was recorded from the left seminal vesicle, the right vas deferens, the bladder, and the cavernous bodies. The vas deferens was also perfused with warm saline (0.068 ml/min) cording (Fig. 2). The tubing was filled with heparinized saline to prevent clotting. Bilateral sympathetic trunk, hypogastric nerve, and unilateral cavernous nerve stimulations were done independently. The hypogastric nerves and sympathetic trunks were also stimulated uring erection in- duced by cavernous nerve stimulation. Neurophysiology of the lower urinary tract In eight rabbits, a 3-F catheter was placed transurethrally into the blad- der (Fig. 2). The catheter was connected to a fluid-filled line via a three- way stopcock, which allowed for bladder filling and emptying. The bladder was emptied (volume 15 - 140 ml) and bladder capacity was de- termined cystometrically. All stimulations were done after the bladder had been filled to three-quarters of its capacity with warm saline. Bilat- eral sympathetic trunk, hypogastric nerve, and cavernous nerve stimula- tion were done independently. Stimulations of one or both pelvic nerves Intraluminal pressure (cm H20) 40 I 30 20 10 0 Hypogastric nerve A stimulation 30 s ,ol/ o 30 Intraluminal pressure 20 (cm H20) lO (3 30 s Hypogastric nerve stimulation Cavernous nerve R stimulation Fig. 3. A Stimulation of the hypogastric nerves or sympathetic trunks induced contraction of seminal vesicles. B Concomitant cavernous nerve stimulation reduced the pressure elevation provoked by hypogastric nerve stimulation, but this reduction was reversible on ter- mination of cavernous timulation lation of the hypogastric nerves and sympathetic trunks induced a mean pressure increase of 8.5 cm H20. Neurophysiology of the erectile system The baseline intracavernous pressure was 13-24 (mean 19) cm H20. Stimulation of the sympathetic trunks in- duced visible penile shrinkage and an intracavernous pressure increase of 4 -11 (mean 6) cm H20. Unilateral stimulation of the hypogastric nerves (duration 60 s) re- suited in penile protrusion and moderate tumescence without intracavernous pressure changes. Stimulation of the cavernous nerve induced full penile erection, with an intracavernous pressure of 105-125 (mean 113) cm H20 (Fig. 4). The erectile response to cavernous nerve stimula- tion was not changed by either previous or concomitant hypogastric stimulation. Stimulation of the sympathetic trunks during full erection induced by cavernous nerve stimulation abolished the erection in five of eight rabbits. In the remaining three animals, it did not reduce the in- tracavernous pressure during cavernous nerve stimula- tion. Neurophysiology of the lower urinary tract After the bladder had been slowly filled to three-quarters of its capacity, the intravesical pressure was 3 -7  (mean 4) cm H20. Stimulation of the hypogastric nerves, sym- pathetic trunks, or cavernous nerves had no effect. Uni- lateral stimulation of the pelvic nerve induced an in- travesical pressure increase of 7-11 (mean 9.6) cm H20 (Fig. 5). Bilateral stimulation of the pelvic nerves resulted in an intravesical pressure increase of 11 - 15 (mean 13.2) cm H20. The difference between the increases induced by unilateral and bilateral pelvic nerve stimulation was statistically significant (P<0.05). Stimulation of the sympathetic trunks before and/or during unilateral or bi- lateral pelvic nerve stimulation did not influence the in- travesical pressure in comparison with pelvic nerve stimu- lation alone. Discussion To date, the monkey has been the preferred animal model for the study of the neurophysiology of ejaculation be- cause of the similarities between its ejaculatory system and that of man [1]. 235 Electrical stimulation of the hypogastric nerves or sympathetic trunks in the present study resulted in con- traction of the seminal vesicles and vasa deferentia, fol- lowed by the emission of semen. These observations in the rabbit are in accord with the findings of Brindley [1], who described ejaculation provoked by sympathetic trunk stimulation in monkeys. The reason for the de- crease in intraluminal pressure induced by cavernous nerve stimulation (see Fig. 3 B) is speculative. It may have been due to an enlargement of the opening of the seminal vesicle into the prostatic urethra during the erectile re- sponse or to a reflexogenic nhibition of the contraction via an afferent nerve pathway. As in other species [13, 21] cavernous nerve stimula- tion induced full penile erection in rabbits, with an in- tracavernous pressure of about 90~ of the systemic blood pressure. Intracavernous pressure recording in the rat is difficult, and measurements are less reliable than those obtained in the rabbit (penile length > 2 cm in the erect state). The rabbit presents everal advantages over the dog, which is an animal model commonly used for the study of erection. As in man, the rabbit corpora communicate, whereas the dog has two separate corpora, with venous drainage occurring via the cavernous veins only [2, 7]. The induction of erection in the dog results in penile rigidity with no visible tumescence. In contrast, penile erection in the rabbit is similar to that in man, with visible tumescence and rigidity. The response of the corpora cavernosa to basic pharmacologic substances (epineph- rine, norepinephrine, and acethylcholine) has been stud- ied in detail and correlates well with studies done in hu- mans [18]. Stimulation of the hypogastric nerves induced penile protrusion with a moderate increase in tumescence. Eckhard [9] as well as SjOstrand and Klinge [18] reported full penile tumescence after hypogastric stimulation. This different erectile response may have been due to the volt- age applied. We used 1 -4V,  whereas the above-men- tioned investigators applied supramaximal (15-25V)  voltage, which is less physiologic. As described in dogs [5, 14], stimulation of the sym- pathetic trunks led to penile contraction and abolished the erection induced by cavernous nerve stimulation in more than half of the rabbits in the present study. SjOstrand and Klinge [18] also described a decrease in penile volume in the rabbit after sympathetic trunk stim- 120 Intracavernous 80 / pressure (cm H20 ) 40 0 0 1 min t Cavernous nerve stimulation Fig. 4. Cavernous nerve stimulation induced a rise in intmcavernous pressure to about 90~ of the systemic blood pressure Intravesical pressure (cm H20 ) 15 10 5 0 0 30 s Pelvic nerve stimulation Fig. 5. Pelvic nerve stimulation induced bladder contraction with a mean intravesical pressure increase of 9.6 cm H20 236 ulation. This is an important finding, considering the well-known effect of stress on erection and its possible role in psychogenic mpotence. The rabbit does not mark his territory with urine and can store great amounts. This behavior may be responsi- ble for the thin bladder wall and the relatively low in- travesical pressure that occurs during bladder contrac- tions induced by pelvic nerve stimulation. In the dog, sympathetic stimulation before and during pelvic nerve stimulation increases the intravesical pressure over the level reached by pelvic nerve stimulation alone (unpub- lished results). In contrast, this combined stimulation does not change the intravesical pressure response in the rabbit. Our results indicate that the rabbit may be a useful animal model for the study of the physiology and pathophysiology of ejaculatory and erectile systems in man. It also has the advantages of ready availability and low cost. However, important differences between species must be considered, e.g., hypogastric stimulation induces penile tumescence in rabbits but not in dogs or monkeys. Due to its large bladder capacity and low pressure re- sponse to pelvic nerve stimulation, the rabbit does not seem to be a suitable model for the study of human blad- der (dys)function. Acknowledgement. Dr  Stief is the recipient of a grant from the Deutsche Forschungsgemeinschaft. References 1. Brindley G (1981) Electroejaculation: its technique, neurological implication and use. J Neurol Neurosurg Psychiatry 44:9 2. Carati C J, Creed KE, Keogh EJ (1987) Autonomic ontrol of penile erection in the dog. J Physiol 384:525 3. Clark JT, Smith EP, Davidson JM (1985) Evidence for the modula- tion of sexual behavior by alpha-adrenoreceptors in male rats. Neuroendocrinology 41:36 4. Dail WG, Evan AP (1974) Experimental evidence indicating that the penis of the rat is innervated by short adrenergic neurons. Am J Anat 141:203 5. Diederichs W, Stief CG, Benard F, Bosch RJLH, Lue TF, Tanagho EA (1988) Sympathetic effect on erection in dogs and monkeys: J Urol 139:253A 6. Domer FR, Wessler G, Brown RL, Charles HC (1978) Involvement of the sympathetic nervous ystem in the urinary bladder internal sphincter and in penile erection in the anesthetized cat. Invest Urol 15:404 7. Dorr LD, Brody MJ (1967) Hemodynamic mechanisms of erection in the canine penis. Am J Physiol 213:1526 8. Eckhard C (1863) Untersuchungen iiber die Erektion des Hundes. Beitr Anat Physiol 3:123 9. Eckhard C (1876) Qber den Verlauf der nn. erigentes innerhalb des Rtickenmarkes und Gehirns. Beitr Anat Physiol 3:69 10. Groat WC de, Ryall RW (1967) An excitatory action of 5-hydroxytryptamine on sympathetic preganglionic neurons. Exp Brain Res 3:299 11. Henderson VE, Roepke MH (1933) On the mechanisms of erection. Am J Physiol 106:441 12. Langley JN, Anderson HK (1895-1896) The innervation of the pelvic and adjoining viscera: III. The external generative organs. J Physiol 19:85 13. Lue TF (1986) The mechanism of penile erection in the monkey. Semin Urol 4:217 14. Lue TJ, Takamura T, Schmidt RA, Palubkinskas AJ, Tanagho EA (1983) Hemodynamics of erection in the monkey. J Urol 130:1237 15. Nadelhalft I, Groat WC de, Morgan C (1980) Location and mor- phology of parasympathetic preganglionic neurons in the sacral spinal cord of the cat revealed by retrograde axonal transport of horseradish peroxidase. J Comp Neurol 193:265 16. Semans JH, Langworthy OR (1938) Observation on the neurophysiology of sexual function in the male cat. J Urol 40:836 17. Siroky MB, Krane RJ (1983) Neurophysiology of erection. In: Krane RJ, Siroky MB, Goldstein I (eds) Male sexual dysfunction. Little Brown, Boston, pp 9-21 18. SjOstrand NO, Klinge E (1979) Principal mechanisms controlling penile retraction and protrusion in rabbits. Acta Physiol Scand 106:199 19. SjOstrand NO, Klinge E (1979) Changes in penile volume during some cardiovascular reflexes and reactions in rabbit. Acta Physiol Scand 106:327 20. Steers WD, McConnel J, Benson G (1984) Some pharmacologic ef- fect of yohimbine on human and rabbit penis. J Urol 131:799 21. Steers WD, Mallory B, Groat WC de (1987) Electrophysiological analysis of penile reflexes in the rat. J Urol 137:376A 

(1863) Untersuchungen iiber die Erektion des Hundes.

(1876) Qber den Verlauf der nn. erigentes innerhalb des Rtickenmarkes und Gehirns.

An excitatory action of 5-hydroxytryptamine on sympathetic preganglionic neurons.

Anderson HK (1895-1896) The innervation of the pelvic and adjoining viscera: III. The external generative organs.

Autonomic control of penile erection in the dog.

Changes in penile volume during some cardiovascular reflexes and reactions in rabbit.

Electroejaculation: its technique, neurological implication and use.

Electrophysiological analysis of penile reflexes in the rat.

Evidence for the modulation of sexual behavior by alpha-adrenoreceptors in male rats.

Experimental evidence indicating that the penis of the rat is innervated by short adrenergic neurons.

Hemodynamic mechanisms of erection in the canine penis.

Involvement of the sympathetic nervous system in the urinary bladder internal sphincter and in penile erection in the anesthetized cat.

Location and morphology of parasympathetic preganglionic neurons in the sacral spinal cord of the cat revealed by retrograde axonal transport of horseradish peroxidase.

Neurophysiology of erection. In: Krane RJ, Siroky MB, Goldstein I (eds) Male sexual dysfunction. Little Brown,

Observation on the neurophysiology of sexual function in the male cat.

On the mechanisms of erection.

Principal mechanisms controlling penile retraction and protrusion in rabbits.

Some pharmacologic effect of yohimbine on human and rabbit penis.

Tanagho EA

The mechanism of penile erection in the monkey.

The rabbit as a model for neurourologic studies of the lower genitourinary tract

Universität München: Elektronischen Publikationen

World J Urol (1990) 8:233-236 
Free paper ~alof 1' 1 Urology 
World Journal of 
9 Springer-Verlag 1990 
The rabbit as a model for neurourologic studies 
of the lower genitourinary tract* 
C h r i s t i a n  G. Stief**, F ranco i s  Benard ,  R u u d  J. L. H.  Bosch, Sher i f  R. Abose i f ,  a n d  E m i l  A.  Ta na gho  
Department of Urology, University of California, School of Medicine, San Francisco, CA 94143, USA 
Summary.  We evaluated the rabbit  as an  animal  model  
for the elucidat ion of  the neurophysiology of erection, 
ejaculat ion,  and  b ladder  funct ion.  In  24 rabbits, s t imula-  
t ion  of  the hypogastr ic  nerves resulted in penile tumes-  
cence and  cont rac t ion  of  the seminal  vesicles and  vasa 
deferentia. S t imula t ion  of the sympathet ic  t runks  in- 
duced cont rac t ion  of  the penis, seminal  vesicles, and  vasa 
deferentia. Cavernous nerve s t imula t ion  induced penile 
erection with a mean  intracavernous pressure of  113 cm 
H20. Pelvic nerve s t imula t ion  elicited bladder  contrac-  
t ion, bu t  the in t ra lumina l  pressure was low (mean, 9.6 cm 
H20  ) in compar i son  with tha t  in other species. Our  re- 
suits indicate that  the rabbit  may be an appropriate,  rela- 
tively inexpensive, and  readily available model  for the 
study of  e jaculatory and  erectile systems in  man.  Howev- 
er, because of  anatomic  variations,  the rabbi t  b ladder  ap- 
pears to be unsui table  for comparat ive studies in  humans .  
Eckhard [8] first described the appl ica t ion of  m o d e r n  
electrophysiologic methods  to the penile erectile system 
of  dogs in his classic article of  1863. After  dissection, so- 
matic  and  au tonomic  nerves were s t imulated and  the 
erectile response was recorded. The same au thor  reported 
similar experiments in  the rabbi t  13 years later [9]. Since 
then, similar neurourologic  experiments have been de- 
scribed in  dogs [2, 7, 11, 12, 17], monkeys [14], cats [6, 
10, 15, 16], rabbits [18 -20] ,  and rats [3, 4, 21]. 
A n i m a l  studies are necessary for an under s t and ing  of  
the neurophysiology of  the lower geni tour inary  tract and  
for assessment of  the effect of  different types of  treat- 
ment.  In  recent years, ethical and f inancia l  considerat ions 
have reduced the n u m b e r  of  such studies. The rabbi t  is 
similar to the rat in  cost and  availability, bu t  its greater 
* This work was supported by grants from the Deutsche Forschungsge- 
meinschaft (DFG Sti 96/1 und Sti 96/2-1). 
** To whom correspondence should be addressed at: Klinik ftir Urolo- 
gie, Medizinische Hochschule, Konstanty-Gutschow-Strasse 8, W-3000 
Hannover 1, Federal Republic of Germany 
size offers more ease in dissection and  in the recording of  
biologic effects. We under took  this s tudy to evaluate the 
rabbi t  as a possible an imal  model  for the s tudy of  the 
neurophysiology of  the lower gen i tour inary  tract. 
Materials  and m e t h o d s  
A total of 24 white New Zealand rabbits weighing 2.8 - 3.5 kg were used. 
After they had been given adequate anesthesia with i.p. pentobarbital 
(40 mg/kg), the rabbits were placed in a supine position on a heating 
pad. Anesthesia was maintained with 6.5 mg i.v. bolus injections of pen- 
tobarbital as needed, and the rabbits received warm saline i.v. 
(2 ml/kg-~/h- 1). The animals breathed spontaneously. Systemic blood 
pressure was monitored through a 22-gauge angiocatheter in the left 
femoral artery. 
The abdomen was opened by a midline incision. The rectum was 
double-ligated and severed, and the mesentery of the proximal rectum 
and distal colon was dissected up to the inferior mesenteric artery. The 
distal colon was then placed in the upper abdomen. Hypogastric nerves, 
sympathetic trunks at the level of L6-S 1, pelvic nerves (distal to the 
branching of the cavernous nerve), and cavernous nerves were dissected. 
Custom-made electrodes (coated platinum-iridium wires and medical 
quality silastic) were placed around these structures (Fig. 1). Stimula- 
tion parameters were: 1-4 V, 20 Hz frequency, 1 ms pulse width, and 
30-s duration. The abdomen was filled with paraffin oil at 37 ~ Addi- 
tional heat was provided with a heating lamp. Three sets of experiments 
were done. 
Neurophysiology of  the ejaculator), system 
In eight rabbits, a 21-gauge needle was inserted into a seminal vesicle 
for pressure monitoring. A 25-gauge needle was placed into one of the 
vasa deferentia and then connected to a T-tube for continuous perfusion 
of warm saline (Harvard Apparatus; perfusion rate 0.068 ml/min) and 
simultaneous pressure recording (Fig. 2). Bilateral sympathetic trunks, 
hypogastric nerves, and cavernous nerves were independently stimulat- 
ed and the response of the vas deferens and seminal vesicle was record- 
ed. If the seminal vesicle contracted, the expulsed volume was replaced 
with warm saline. The first ejaculate was evaluated for the presence of 
sperm by optic microscopy (X 200). Simultaneous stimulations of the 
cavernous nerves and hypogastric nerves were also done. 
Neurophysiology o f  the erectile system 
The cavernous bodies were freed from the penile skin in eight rabbits. 
A 21-gauge needle was inserted into one cavernous body for pressure re- 
234 
~ trunk 
~ o g a s t  ric trunk 
~ Cavernous nerve 
J Urogenital artery 
Fig. 1. Cus tom-made electrodes are placed around both sympathetic 
trunks,  the hypogastric nerves, the left pelvic nerve, and the left cavern- 
ous nerve 
were done either alone or simultaneously with stimulation of  the 
hypogastric nerves or sympathetic trunks. 
All catheters and fluid-filled lines were connected to a Sta tham 
(model 23 BC) transducer for pressure recording (Grass Polygraph mod-  
el 7). All stimulations or stimulation combinat ions were repeated three 
t imes in each rabbit and the results are expressed as the mean of  these 
findings. Statistical analysis was done using Student 's  t-test. 
Results 
Neurophysiology of the ejaculatory system 
Baseline pressure within the seminal vesicles was 2 - 7  
(mean 4) cm H20. Stimulation of  the hypogastric nerves 
induced contraction of  the seminal vesicles in all rabbits, 
with an intraluminal pressure of  2 3 - 3 7  (mean 28) cm 
HzO (Fig. 3A). This contraction was accompanied by 
emission of a white, sperm-containing fluid. The same re- 
sponse was observed after both sympathetic combined 
hypogastric and sympathetic stimulation. Stimulation of  
the cavernous nerve alone did not influence the in- 
traluminal pressure. However, when the cavernous nerve 
was stimulated before and/or  during seminal vesicle con- 
traction, the intraluminal peak pressure was reduced by a 
mean of  7 cm H20  (Fig. 3 B). 
During perfusion, the intraluminal pressure of  the vas 
deferens was 14-23  (mean 20) cm H20. Spontaneous 
contractions with an interval of  1 5 - 4 5  s between each 
wave and a mean pressure increase of  8 cm H20  were re- 
corded. Stimulation of  the hypogastric nerves induced an 
intraluminal pressure increase of  8 - 1 1  (mean 9.3) cm 
H20, and stimulation of  the sympathetic trunks induced 
a mean pressure increase of  8 cm H20. Combined stimu- 
Fig. 2. Intraluminal pressure was recorded from the left seminal vesicle, 
the right vas deferens, the bladder, and the cavernous bodies. The vas 
deferens was also perfused with warm saline (0.068 ml /min)  
cording (Fig. 2). The tubing was filled with heparinized saline to prevent 
clotting. Bilateral sympathetic trunk,  hypogastric nerve, and unilateral 
cavernous nerve stimulations were done independently. The hypogastric 
nerves and sympathetic t runks were also stimulated during erection in- 
duced by cavernous nerve stimulation. 
Neurophysiology of the lower urinary tract 
In eight rabbits, a 3-F catheter was placed transurethrally into the blad- 
der (Fig. 2). The catheter was connected to a fluid-filled line via a three- 
way stopcock, which allowed for bladder filling and emptying. The 
bladder was emptied (volume 15 - 140 ml) and bladder capacity was de- 
termined cystometrically. All stimulations were done after the bladder 
had  been filled to three-quarters of  its capacity with warm saline. Bilat- 
eral sympathetic trunk, hypogastric nerve, and cavernous nerve stimula- 
tion were done independently. Stimulations of one or both  pelvic nerves 
Intraluminal 
pressure 
(cm H20) 
40 I 30 
20 
10 
0 
Hypogastric nerve 
A stimulation 
30 s 
,ol/ o 30 Intraluminal pressure 20 
(cm H20) 
lO 
(3 30 s Hypogastric nerve 
stimulation 
Cavernous nerve 
R stimulation 
Fig. 3. A Stimulation of  the hypogastric nerves or sympathetic t runks  
induced contraction of  seminal vesicles. B Concomitant  cavernous 
nerve stimulation reduced the pressure elevation provoked by 
hypogastric nerve stimulation, but  this reduction was reversible on ter- 
minat ion of cavernous st imulation 
lation of the hypogastric nerves and sympathetic trunks 
induced a mean pressure increase of 8.5 cm H20. 
Neurophysiology of the erectile system 
The baseline intracavernous pressure was 13 -24  (mean 
19) cm H20. Stimulation of  the sympathetic trunks in- 
duced visible penile shrinkage and an intracavernous 
pressure increase of 4 - 1 1  (mean 6) cm H20. Unilateral 
stimulation of  the hypogastric nerves (duration 60 s) re- 
suited in penile protrusion and moderate tumescence 
without intracavernous pressure changes. Stimulation of  
the cavernous nerve induced full penile erection, with an 
intracavernous pressure of 105-125 (mean 113) cm H20 
(Fig. 4). The erectile response to cavernous nerve stimula- 
tion was not changed by either previous or concomitant 
hypogastric stimulation. Stimulation of the sympathetic 
trunks during full erection induced by cavernous nerve 
stimulation abolished the erection in five of eight rabbits. 
In the remaining three animals, it did not reduce the in- 
tracavernous pressure during cavernous nerve stimula- 
tion. 
Neurophysiology of the lower urinary tract 
After the bladder had been slowly filled to three-quarters 
of  its capacity, the intravesical pressure was 3 - 7  (mean 
4) cm H20. Stimulation of  the hypogastric nerves, sym- 
pathetic trunks, or cavernous nerves had no effect. Uni- 
lateral stimulation of  the pelvic nerve induced an in- 
travesical pressure increase of 7 - 1 1  (mean 9.6) cm H20 
(Fig. 5). Bilateral stimulation of  the pelvic nerves resulted 
in an intravesical pressure increase of 11 - 15 (mean 13.2) 
cm H20. The difference between the increases induced 
by unilateral and bilateral pelvic nerve stimulation was 
statistically significant (P<0.05).  Stimulation of the 
sympathetic trunks before and/or  during unilateral or bi- 
lateral pelvic nerve stimulation did not influence the in- 
travesical pressure in comparison with pelvic nerve stimu- 
lation alone. 
Discussion 
To date, the monkey has been the preferred animal model 
for the study of  the neurophysiology of  ejaculation be- 
cause of the similarities between its ejaculatory system 
and that of man [1]. 
235 
Electrical stimulation of  the hypogastric nerves or 
sympathetic trunks in the present study resulted in con- 
traction of  the seminal vesicles and vasa deferentia, fol- 
lowed by the emission of  semen. These observations in 
the rabbit are in accord with the findings of  Brindley [1], 
who described ejaculation provoked by sympathetic 
t runk stimulation in monkeys. The reason for the de- 
crease in intraluminal pressure induced by cavernous 
nerve stimulation (see Fig. 3 B) is speculative. It may have 
been due to an enlargement of the opening of the seminal 
vesicle into the prostatic urethra during the erectile re- 
sponse or to a reflexogenic inhibition of  the contraction 
via an afferent nerve pathway. 
As in other species [13, 21] cavernous nerve stimula- 
tion induced full penile erection in rabbits, with an in- 
tracavernous pressure of  about 90~ of the systemic 
blood pressure. Intracavernous pressure recording in the 
rat is difficult, and measurements are less reliable than 
those obtained in the rabbit (penile length > 2 cm in the 
erect state). 
The rabbit presents several advantages over the dog, 
which is an animal model commonly used for the study 
of  erection. As in man, the rabbit corpora communicate, 
whereas the dog has two separate corpora, with venous 
drainage occurring via the cavernous veins only [2, 7]. 
The induction of  erection in the dog results in penile 
rigidity with no visible tumescence. In contrast, penile 
erection in the rabbit is similar to that in man, with visible 
tumescence and rigidity. The response of  the corpora 
cavernosa to basic pharmacologic substances (epineph- 
rine, norepinephrine, and acethylcholine) has been stud- 
ied in detail and correlates well with studies done in hu- 
mans [18]. 
Stimulation of  the hypogastric nerves induced penile 
protrusion with a moderate increase in tumescence. 
Eckhard [9] as well as SjOstrand and Klinge [18] reported 
full penile tumescence after hypogastric stimulation. This 
different erectile response may have been due to the volt- 
age applied. We used 1 - 4 V ,  whereas the above-men- 
tioned investigators applied supramaximal ( 1 5 - 2 5 V )  
voltage, which is less physiologic. 
As described in dogs [5, 14], stimulation of the sym- 
pathetic trunks led to penile contraction and abolished 
the erection induced by cavernous nerve stimulation in 
more than half of  the rabbits in the present study. 
SjOstrand and Klinge [18] also described a decrease in 
penile volume in the rabbit after sympathetic t runk stim- 
120 
Intracavernous 80 / 
pressure 
(cm H20 ) 40 
0 
0 1 min 
t 
Cavernous nerve 
stimulation 
Fig. 4. Cavernous nerve st imulation induced a rise in intmcavernous 
pressure to about  90~ of  the systemic blood pressure 
Intravesical 
pressure 
(cm H20 ) 
15 
10 
5 
0 
0 30 s 
Pelvic nerve 
stimulation 
Fig. 5. Pelvic nerve st imulation induced bladder contraction with a 
mean  intravesical pressure increase of 9.6 cm H20  
236 
ulation. This is an important finding, considering the 
well-known effect of stress on erection and its possible 
role in psychogenic impotence. 
The rabbit does not mark his territory with urine and 
can store great amounts. This behavior may be responsi- 
ble for the thin bladder wall and the relatively low in- 
travesical pressure that occurs during bladder contrac- 
tions induced by pelvic nerve stimulation. In the dog, 
sympathetic stimulation before and during pelvic nerve 
stimulation increases the intravesical pressure over the 
level reached by pelvic nerve stimulation alone (unpub- 
lished results). In contrast, this combined stimulation 
does not change the intravesical pressure response in the 
rabbit. 
Our results indicate that the rabbit may be a useful 
animal model for the study of the physiology and 
pathophysiology of ejaculatory and erectile systems in 
man. It also has the advantages of ready availability and 
low cost. However, important differences between species 
must be considered, e.g., hypogastric stimulation induces 
penile tumescence in rabbits but not in dogs or monkeys. 
Due to its large bladder capacity and low pressure re- 
sponse to pelvic nerve stimulation, the rabbit does not 
seem to be a suitable model for the study of human blad- 
der (dys)function. 
Acknowledgement. Dr. Stief is the recipient of  a grant from the 
Deutsche Forschungsgemeinschaft. 
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The rabbit as a model for neurourologic studies of the lower genitourinary tract

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