Hemodynamics of Pelvic Nerve Induced Erection in a Canine Model. I. Pressure and Flow

0022-534 7/90/1443-0794$02.00/0 Vol. 144, September Printed in U.S.A.

THE JOURNAL OF UROLOGY

Copyright© 1990 by AMERICAN UROLOGICAL ASSOCIATION, INC.

HEMODYNAMICS OF PELVIC NERVE INDUCED ERECTION IN A CANINE MODEL. L PRESSURE AND FLOW Y. V ARDI*

AND

M. B. SIROKY

From the Urology Section/Department of Surgery, Veterans Affairs Medical Center, Boston, Massachusetts

ABSTRACT

Using a previously developed canine model of erection, we measured pudendal artery and venous flow as well as pressure in the corpora cavernosa, glans penis, pudenda! artery and vein. Penile erection was induced by pelvic nerve stimulation. Arterial flow increased by a factor of 2.5 within two seconds after the onset of stimulation. This was followed by a similar increase in venous flow about one second later. Spongiosal pressure began to rise about six seconds after nerve stimulation and always remained below cavernosal pressure. Cavernosal pressure began to rise after a latency of about 11 seconds. This latency period is accounted for by relaxation of the smooth muscle of the cavernosal sinusoids. Spongiosal pressure is maintained primarily by a high flow state through the glans penis while cavernosal pressure depends on a veno-occlusive mechanism. (J. Ural., 144: 794797, 1990) Penile erection is widely recognized to involve increased arterial inflow to the cavernosal space. A mechanism for regulating cavernosal outflow is also postulated. Although much has been learned from recent investigation in this area, many aspects of erectile physiology remain unclear. Since hemodynamic studies during erection are difficult in humans, animal models are commonly used in studies of erectile physiology. We have described a canine model that permits study of arterial, venous and cavernosal changes during nerve induced erection.1· 2 In the present study, we report the results of hemodynamic measurements in our canine model with particular emphasis on the changes in arterial and venous flow as well as intracavernosal pressure.

consists of multiple fine fibers coursing in the pararectal and paraprostatic fascia. The pelvic nerve was exposed unilaterally by tying and dividing the prostatic artery and vein as they lie superficial to the nerve. A Harvard subminiature electrode was placed around the pelvic nerve bundle proximal to the junction of the hypogastric nerve. The hypogastric nerves were divided bilaterally but the pelvic nerves were left intact. Unilateral pelvic nerve stimulation produced excellent bladder contraction as well as penile erection. There was no significant advantage to bilateral nerve stimulation. To prevent interference with HEMODYNAMICS OF ERECTION GLANS PENIS ---~

MATERIALS AND METHODS

Twenty-six male mongrel dogs weighing between 20 and 30 kg. were used. Anesthesia was induced with pentobarbital 30 mg./kg. intravenously and maintained with additional doses as required. The animals were placed on assisted ventilation using room air via an endotracheal cannula and hydrated with lactated Ringer's solution at 125 ml./hour. Systemic blood pressure was monitored via a cannula placed in the internal carotid artery. A 20 F tube was placed into the bladder via a cystotomy for urinary drainage. Flow measurements (fig. 1). Flow was measured by placing an appropriately sized blood flow probe around the internal iliac artery (1.5 mm.) or internal iliac vein (2.0 mm.). Since the internal pudendal artery is a major branch of the internal iliac artery, it was converted into an end vessel supplying the penis by tying the caudal gluteal and vesico-prostatic branches. In addition, the dorsal penile arteries, the major blood supply to the glans penis, were tied near the base of the penis (fig. 1). In most cases the dorsal penile veins were also tied but in some cases the dorsal veins were not ligated to observe the effect of unrestricted venous flow from the glans penis. Branches of the internal pudendal vein in the pelvis were ligated on the side bearing the flow probe. The contralateral internal iliac vein was tied to shunt venous flow to the side bearing the flow probe. All flow measurement were made using a two channel electromagnetic flow meter (Biotronix, Kensington, Md.). Pelvic nerve stimulation (PNS). The canine pelvic nerve Accepted for publication May 22, 1990. *Requests for reprints: Urology Section, VA Medical Center, 150 S. Huntington Avenue, Boston MA 02130. Supported by the Veterans Affairs Central Office.

PROSTATE

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\ ) CORPORAL I INTERNAL ILIAC ARTERY

~ PRESSURE CAUDAL GLUTEAL ARTERY

FIG. 1. Semi-schematic depiction of techniques used to measure hemodynamic changes during pelvic nerve induced erection. Major branches of the internal iliac artery are pudenda!, caudal gluteal (tied) and vesicoprostatic (not labeled; tied) arteries. Corporal pressure was measured in each cavernosal space separately but only one side is shown. Line used to measure pressure in glans penis is not shown. Corporal perfusion line shown in figure was not used in this series of experiments.

blood flow recording, flow measurement was carried out on one side of the pelvis while nerve stimulation was performed on the contralateral side. Square wave unidirectional stimulation was delivered for 25 seconds using a Grass SD-9 stimulator. Stimulation parameters were as follows: eight ms duration, supramaximal voltage (four to eight volts) at various frequencies. Pressure measurement. Intracavernosal and intraspongiosa! pressure were measured by placing an 18 G needle directly into the appropriate corporal space. In some animals, after dividing the dorsal arteries and veins near the base of the penis, 22 G

794

795

HEMODYNAMICS OF ERECTION

Data analysis. The latency was defined as the time from onset of stimulation to the point at which an increase in the measured parameter above baseline value could be observed. The rise time was defined as the time from the end of the latency period to the peak value. Total time was the time from the onset of stimulation to the point at which the parameter returned to within 10% of the baseline value.

BLOOD PRESSURE mm Hg

50

ARTERY FLOW

RESULTS ml/min

VEIN FLOW

RIGHT CORPORAL PRESSURE mm Hg

O

LEFT CORPORAL PRESSURE mm Hg

SPONGIOSUM PRESSURE mm Hg

FIG. 2. Measurement of multiple parameters during pelvic nerve induced erection in canine model, including (from above down) systemic blood pressure, pudenda! arterial flow, pudenda! venous flow, right intracorporal pressure, left intracorporal pressure, corpus spongiosum pressure. Note that, long after intracavernosal pressure has returned to baseline, spongiosal pressure remains elevated as long as dorsal veins are occluded. Opening of dorsal veins (down arrow) immediately results in venous flow spike and fall in spongiosal pressure to baseline. STIM = period of pelvic nerve stimulation.

plastic cannulae were placed into the proximal stumps of these vessels for pressure measurement. Since the dorsal arteries and veins are branches of the pudendal vessels, this allowed monitoring of pressure changes in the pudendal arteries and veins. Recording methods. An eight channel heat writing physiologic recorder (Hewlett-Packard, Lexington, Mass.) was used to obtain permanent records of pressure in each corpus cavernosum, the corpus spongiosum, pelvic arteries and pelvic veins, pudenda! arterial flow, pudendal venous flow, systemic blood pressure and electrocardiogram. TABLE 1.

Flow changes. Following the onset of pelvic nerve stimulation (PNS), a large and rapid increase in flow through the internal pudenda! artery and vein was observed (fig. 2). As summarized in table 1, there is a latency period of about two seconds following the onset of PNS before arterial flow begins to increase. Arterial flow increased from 24.4 ± 2.8 ml./min. (mean ± SEM) to 61.5 ± 5.3 ml./min. in less than five seconds. With the dorsal veins occluded, increased venous flow can be detected after about 3. 7 seconds and reaches a peak after 11 seconds. Spongiosal pressure changes (table 2). A pressure increase occurred earliest in the corpus spongiosum, beginning after a latency of 6.2 ± 3.6 seconds and reaching a peak of 58.3 ± 10.5 mm. Hg. Pressure in the spongiosal space remained elevated as long as the dorsal veins remained occluded (fig. 2). In contrast, cavernosal pressure was unaffected by occlusion of the dorsal veins. Opening the dorsal veins to the atmosphere resulted in an immediate fall in spongiosal pressure to baseline value but did not affect intracavernosal pressure. Intracavernosal pressure changes (table 2). Pressure in the corpus cavernosum did not begin to increase until 11.2 ± 4.4 seconds after pelvic nerve stimulation. In most cases this interval was occupied by a slight but noticeable pressure fall in both cavernosal spaces (fig. 3). Pressure in the corpora cavernosa reached a peak of 112.1 ± 19.2 mm. Hg. Slight differences in peak pressure between the two corpora were regularly observed. Arterial and venous pressure (figure 3). Arterial pressure fell by approximately 25% coincident with the increase in arterial flow. In fact, the arterial pressure tracing appeared to be a mirror image of the flow tracing. The fall in arterial pressure also coincided with the slight fall in corporal pressure that precedes the corporal pressure increase (fig. 3). Venous pressure increased slightly in conjunction with increase venous flow. Effect of stimulation frequency (figure 4). The best response was obtained at eight or 16 Hertz with much less response at frequencies higher or lower than this range. The corporal pressure increase appeared to be the most sensitive to stimulation frequency. Effect of repeated stimulation (figure 5). Repeated nerve stimulation was able to reproduce the arterial and venous flow increases. However, once the cavernosal pressure rose to its maximum, repeated nerve stimulation produced minimal changes in intracavernosal pressure. In particular, decline in

Arterial and venous flow during pelvic nerve induced erection (n

= 42/24)

Flow (ml./min.)

Flow Measured

Response Latency (s)

Rise Time (s)

Total Time (s)

Baseline

Peak

Percent Change

Arterial Venous DVopen DV closed

2.2 ± 0.2

4.7 ± 0.4

76.7 ± 7.8

24.4 ± 2.8

61.5 ± 5.3

+152%

3.7 ± 0.2 3.3 ± 0.4

11.0 ± 0.5 39.3 ± 4.7

100.4 ± 8.7 170.0 ± 36.5

29.5 ± 2.5 29.5 ± 2.5

72.9 ± 4.5 103.0 ± 7.2

+147% +249%

Mean ± SEM, n

= # measurements/# animals, DV = dorsal veins. TABLE

2. Intracorporal pressure changes following pelvic nerve stimulation Pressure (mm. Hg)

Location of Measurement Corpus cavernosum (n = 80/26) Corpus spongiosum (n = 11/6) Mean ± SEM, n

= # measurements/# animals.

Latency (s)

Rise Time (s)

11.2 ± 4.4 6.2 ± 3.6

29.1 ± 7.2 33.2 ± 5.0

Baseline

Peak

17.5 ± 4.3 9.0 ± 2.1

112.1 ± 19.2 58.3 ± 10.5

796

VARDI AND SIROKY

SPONGIOSUM

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ARTERY FLOW

PRESSURE

25

ml/min

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50

VEIN FLOW

25

ml/min

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250

LEFT CORPORAL PRESSURE

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mm Hg

PELVIC ARTERY PRESSURE

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250

BLOOD PRESSURE .

0

250

RIGHT CORPORAL PRESSURE

O

ECG

2000 [

mm Hg

LEFT CORPORAL PRESSURE mm Hg

RIGHT CORPORAL PRESSURE mm Hg

FIG. 5. Effect of multiple stimulation episodes on artery and vein flow, intracavernosal pressure. Note that marked increases as well as decreases in arterial and venous flow have little effect on intracorporal pressure. STIM = pelvic nerve stimulation.

125

0

125

0

FIG. 3. Measurement of same parameters as in figure 2 but also including pelvic arterial pressure and pelvic vein pressure. These pressure were measured by cannulating stump of dorsal artery and vein, respectively. Note time relationship between fall in arterial pressure, increase in arterial flow and initial fall in corporal pressure. Note also fall in corporal pressure immediately following onset of PNS. PNS = pelvic nerve stimulation.

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FIG. 4. Multiple parameters measured during pelvic nerve stimulation at various frequencies. Hz = Hertz STIM = pelvic nerve stimulation.

arterial and venous flow was not associated with any fall in intracavernosal pressure. DISCUSSION

Investigators have described a wide variety of animal models with the aim of studying the hemodynamics of penile erection. 3-6 However, many of these studies were limited by technical or conceptual difficulties. Henderson and Roepke 3 measured intracavernosal pressure and reported that, upon pelvic nerve stimulation, pressure increased until it approximated the pressure in the carotid artery. However, they measured flow in the dorsal penile veins and did not recognize that, in the dog, these veins drain only the glans penis and have no relation to

the corpora cavernosa. In contrast, Deysach4 correctly recognized that the glans penis is a high flow system without venoocclusive characteristics while the corpora cavernosa are low flow, occlusive bodies. His work is among the earliest to emphasize the role of the veno-occlusive mechanism in the corpora cavernosa, especially in species lacking an os penis such as monkey and man. Christensen 5 produced now-classic anatomic studies of the canine penis but focused almost exclusively on engorgement of the glans penis in his discussion of the mechanism of erection. Similarly, Dorr and Brody6 measured only venous return from the dorsal veins and pressure in the glans penis. More recent studies using canine models have resulted in improved hemodynamic measurements (table 3). Lue and associates 7 have described simultaneous measurement of intracavernosal pressure and pudendal blood flow. However, no attempt was made to measure venous outflow directly. In contrast, the model of Andersson and associates 8 measured outflow from the dorsal veins and penile volume change. Arterial inflow, rather than being measured directly, was calculated from these measurements. More importantly, the model of Andersson, like previous studies, is based upon the glans penis rather than the corpus cavernosum. We feel that it is important to use the corpus cavernosum of the dog as a model for human erection since the specialized function of the canine glans penis has no human correlate. Carati and associates" did not measure flow but used dorsal artery pressure as a substitute. Penile erection consists of several distinct hemodynamic components occurring in rapid succession. In order to analyze this process, three parameters relating to the corpus cavernosum must be recorded simultaneously: 1) intracavernosal pressure, 2) arterial inflow, and 3) venous outflow. Simultaneous recording of spongiosal pressure adds further information regarding the events in that system. Of these parameters, the venous outflow from the corpus cavernosum has proved most difficult to measure and has been ignored in most studies. The venous drainage of the glans penis is via the dorsal veins which are constricted by a sub-pubic muscular ring during erection. The corpora cavernosa drain via the deep penile veins which join the dorsal veins to form the internal pudendal vein. Ultimately, the penis drains into the internal iliac veins. Measurement of the venous outflow specif-

797

HEMODYNAMICS OF ERECTION TABLE 3.

Recent quantitative studies of canine penile erection Results

Investigator Lue (1984) Andersson (1984) Carati (1987)

Flow Methods Pudenda! artery pressure and flow Dorsal vein flow; glans volume Dorsal penile artery pressure

ically from the corpus cavernosum requires surgical exclusion of the glans penis as we have described. 2 The arterial supply to the canine penis is primarily via the paired internal pudendal arteries. After giving off the ventral perineal artery, the internal pudendal artery trifurcates to terminate as the artery of the bulb, the deep (cavernosal) artery and the dorsal artery of the penis. The latter artery divides into a deep and superficial branch and is the main blood supply to the bulbus glandis, the specialized erectile tissue of the canine glans penis. Since the dorsal artery of the penis is a branch of the pudenda! artery, cannulating the dorsal artery as described herein permits measurement of pressure in the pudendal artery. Based on our studies, the sequence of events in pelvic nerve induced erection is as follows: arterial flow increases after two seconds and venous flow increases after 3. 7 seconds if the dorsal veins are occluded. This difference of 1. 7 seconds is explained by the time required for blood to circulate through the corpora cavernosa spaces. When the dorsal veins are permitted to drain the glans penis (table 1), a slightly different flow pattern emerges due to the contribution of the glans penis. Venous flow begins to rise after only 3.3 seconds, continues significantly longer and rises to a higher value because of the addition of blood return from the glans penis. Spongiosal pressure begins to rise after 6.2 seconds (table 2) and always reaches a peak well below that in the corpora cavernosa. Once the arterial flow has returned to baseline, opening the dorsal veins abruptly lowers the spongiosal pressure but has no effect on cavernosal pressure. This observation suggests that, while spongiosal pressure depends on the maintenance of a high flow state, this is not true of the corpus cavernosum. As observed by Deysach, 4 the glans penis appears to have no veno-occlusive ability and acts as an arteriovenous fistula during erection. The major physiologic role of this hemodynamic system appears to be to serve as a high flow, low resistance parallel circuit that can supply arterial blood to the cavernosal system as needed. This is shown also by the results of repeated pelvic nerve stimulation (figure 5). Arterial and venous flow rapidly rise and fall in response to nerve stimulation with little influence on the intracavernosal pressure, indicating that most of the excess flow must be routed around rather than through the cavernosal circuit. The last event is the rise in intracavernosal pressure observed after 11.2 seconds. Andersson and associates 8 have suggested that this delay is due to delayed opening of resistance vessels supplying the cavernosal space. We as well as others 7 have observed that most of the cavernosal latency period is occupied by a small drop in intracavernosal pressure (figure 3). The cavernosal pressure drop begins almost immediately after the onset of PNS and occurs at the same time as a profound pressure drop due to vasodilatation occurs in the pudenda! artery. If the hypothesis of Andersson were correct, one would expect to see a pressure drop in the pudenda! artery occur much later to coincide with the opening of resistance vessels and the rise in intracavernosal pressure. This suggests that the latency period is due mostly to relaxation of the smooth muscle of the cavernosal sinusoids and the time required to fill the now compliant cavernosal sinusoids with arterial blood. It must be remembered that the resistance vessels, even when dilated, are small in caliber and will require some time to fill the cavernous

Arterial Flow

Peak Cavernosal Pressure

2.5 fold flow increase 40 mm. Hg pressure drop Not measured

10 mm. Hg< systolic BP

10-40% decrease in pressure

Not measured 60%-100% of mean BP

spaces. These considerations, rather than delayed opening of the resistance vessels, appear to account adequately for the observed latency of corporal erection. Comparing the hemodynamics of the spongiosal and cavernosal systems allows one to appreciate the central role of the veno-occlusive mechanism of the corpora cavernosa. Not only does this mechanism permit the achievement of higher pressure within the cavernosal space than in the spongiosal space, it does so at a flow minimally above baseline flow. It thus permits the maintenance of high intracavernosal pressure with minimal energy expenditure. In addition, the veno-occlusive mechanism acts to convert the corpora cavernosa into closed spaces that can be squeezed by striated perinea! muscles to further increase intracavernosal pressure for short periods of time. While species differences exist, the hemodynamics of the canine corpus cavernosum are comparable in many ways to that of the human and the canine model remains a valuable means of studying erectile physiology. In both species, increased arterial flow characterizes the initiation of erection. 2 • 10 In addition, a veno-occlusive mechanism exists within the corpora cavernosa in both species. Wagner 11 demonstrated decreased outflow from the human penis during full erection. Our results demonstrate the complex and rapid hemodynamic changes induced by pelvic nerve stimulation, elucidate the differing hemodynamic mechanisms of the spongiosal circulation and the cavernosal circulation and emphasize the central role of the veno-occlusive mechanism in the corpora cavernosa. The characteristics of the corporal occlusion mechanism are the subject of current investigation. REFERENCES

1. Vardi, Y., Padma-Nathan, H. and Siroky, M. B.: Hemodynamics of canine penile erection: direct measurement of venous outflow. Surg. Forum, 38: 649, 1987. 2. Vardi, Y. and Siroky, M. B.: A canine model for hemodynamic study of isolated corpus cavernosum. J. Urol., 138: 663, 1987. 3. Henderson, V. E. and Roepke, M. H.: On the mechanism of penile erection: a neuropharmacologic study. Am. J. Physiol., 106: 441, 1933. 4. Deysach, L. J.: The comparative morphology of the erectile tissue of the penis with special emphasis on the probable mechanism of erection. Am. J. Anat., 64: 111, 1939. 5. Christensen, G. C.: Angioarchitecture of the canine penis and the process of erection. Am. J. Anat., 95: 227, 1954. 6. Dorr, L. D. and Brody, M. J.: Hemodynamic mechanisms of erection in the canine penis. Am. J. Physiol., 213: 1526, 1967. 7. Lue, T. F., Takamura, T., Umraiya, M., Schmidt, R. and Tanagho, E.: Hemodynamics of canine corpora cavernosa during erection. Urology, 24: 347, 1984. 8. Andersson, P-0., Bloom, S. R. and Mellander, S.: Haemodynamics of pelvic nerve induced penile erection in the dog: possible mediation by vasoactive intestinal polypeptide. J. Physiol., 350: 209, 1984. 9. Carati, C. J., Creed, K. E. and Keogh, E. J.: Autonomic control of penile erection in the dog. J. Physiol., 384: 525, 1987. 10. Newman, H. F., Northrup, J. D. and Devlin, J.: Mechanism of human penile erection. Invest. Urol., 1, 350, 1964. 11. Wagner, G.: Erection: physiology and endocrinology. In: Impotence: Physiological, Psychological, Surgical Diagnosis and Treatment. Edited by Wagner, G. and Green, R. R. Plenum Press, New York:1981.