Functional Measurements of Penile Erection in Feline, Canine and Primate Animal Models

Functional measurements of penile erection in feline, canine and primate animal models

WJG Hellstrom1*

1Tulane Univeristy Health Sciences Centre, New Orleans, LA, USA

Basic science research on erectile dysfunction (ED) intracavernosally at the end of each experiment to has mainly focused on the mechanisms of corpus serve as a control comparison. In this model, one cavernosal smooth muscle relaxation. Current can measure changes in intracavernosal pressure pharmacotherapy for ED takes advantage of the and penile length, total duration of erectile re- biochemical and physiological mechanisms that sponse, and alterations in systemic arterial blood relax erectile tissue to achieve erectile function pressure (Table 1). The feline model is an excellent suf®cient for normal sexual activity. Animal models animal species to examine the physiology of penile have enabled researchers to carefully study smooth erection because both the cGMP and cAMP second muscle physiology and pharmacology in order to messenger systems are functional in this species and develop speci®c medications for the treatment of are very similar to the erectile mechanisms opera- sexual dysfunction. tional in humans. Other signi®cant advantages of In order to understand the various mechanisms this animal model are the relatively large size of the which govern corpora cavernosal smooth muscle penis and two corpora cavernosa which commu- tone and erectile function, one must investigate a nicate as in the human penis. Hence, one can place a number of variables in a systematic and scienti®c needle in one corpora for measurement of intra- manner. The ®rst animal model that was used to cavernosal pressures, and one can concurrently study the pharmacological effects of different agents inject pharmacological agents into the other corpora on erection was the cat.1 In this model, catheters are and observe instantaneous changes in pressure inserted into the external jugular vein for intrave- measurements. nous administration of drugs and into the carotid Another well-recognized and widely accepted artery for the measurement of systemic arterial model to study the physiology of human erections pressure (Figure 1). A vertical, circumcision-like is the primate model.3 The basic hemodynamics of incision is made to expose the two ventral corpora erection were established in this model, and our cavernosa and the dorsal corpus spongiosum.2 A overall understanding of the erectile process in 30-gauge needle is placed into the right corpus humans has been directly extrapolated from studies cavernosum to permit administration of drugs into performed on primates.4 The major advantages of the penis. A 25-gauge needle is placed midway into the primate model are the large size of the penis and the left corpus cavernosum for the continuous overall comparable penile structural anatomy of the measurement of intracavernosal pressure (mmHg) penis when compared with other laboratory ani- (Figure 1). In experiments in which the transurethral mals. However, there are some obstacles with the administration of a vasoactive agent is employed, use of this species. Problems with the scarcity of drugs are introduced into the urethra via a 20-gauge animals and ®nancial restraints limit the number of Jelco i.v. catheter (Figure 1). Systemic and intra- routine erection studies that can be performed with cavernosal pressures (mmHg) are measured with a the primate. polygraph, and mean pressures are obtained by The canine model has been extremely useful electronic averaging (Figure 1). Penile length (mm) when studying the pharmacokinetics of pharmaco- is measured with a ruler. After dose ± response logical agents and certain histological conditions.5,6 curves for pharmacological agents have been at- It has become the standard model for pharmaceu- tained, a standard control combination of papaver- tical evaluation of the safety and toxicology of ine (1.65 mg), prostaglandin E1 (PGE1) (0.5 mg), and cardiovascular agents. However, the ®rst major phentolamine (25 mg) is prepared and injected disadvantage with the dog is the presence of two separate corpora cavernosa which do not commu- nicate. Researchers must place two needles into the same corpora: one to measure intracavernosal *Correspondence: WJG Hellstrom, Section of Andrology and pressure and the other for drug delivery. Second, Male Infertility, Tulane Univeristy Health Sciences Center, Department of Urology, 1430 Tulane Ave. SL42, New Orleans, there is signi®cant inter-dog variability. Third, the LA 70112, USA. cAMP system is not a predominate second messen- E-mail: [email protected] ger system in canine erectile physiology. Therefore, Functional measurements of erection WJG Hellstrom 150

Figure 1 Components used in feline erection studies. A feline penis; B needle for intracavernosal injection of drugs; C catheter for transurethral delivery of drugs; D catheter connected with pressure transducer for intracavernosal pressure (ICP); E feline neck area; F catheter connected with pressure transducer for systemic arterial pressure (SAP); G catheter for delivering sedation drug; H polygraph.

Table 1 Parameters measured in the feline erection model hemodynamic measurements. One can anticipate (1) Maximal intracavernosal pressure that in the decades to come animal erection models (2) Duration of maximal intracavernosal pressure will likely become more a part of the drug develop- (3) Total duration of erectile response ment process, as scientists search for more selective (4) Changes in penile length pharmaceutical vasoactive agents with improved (5) Systemic arterial blood pressure ef®cacy and fewer side effects.

the dog model is an excellent model for the study of drug pharmacokinetics, but in other areas it is References dif®cult to apply scienti®c data to the human condition. 1 Domer FR, Wessler G, Brown RL, Charles HC. Involvement of In conclusion, each animal model of penile the sympathetic nervous system in the urinary bladder internal erection has contributed something to our under- sphincter and in penile erection in the anesthetized cat. Invest standing about the physiology and pharmacology of Urol 1978; 15: 404 ± 407. human erections. No single animal model will be 2 Wang R et al. Nitric oxide mediates penile erection in cats. J Urol 1994; 151: 234 ± 237. completely satisfactory, therefore we have to recog- 3 Hellstrom WJ et al. Penile erection in the primate: induction nize each of their strengths and limitations. The cat with nitric-oxide donors. J Urol 1994; 151: 1723 ± 1727. and primate are unique from most other animal 4 Lue TF. The mechanism of penile erection in the monkey. models of penile erection in that they both possess Semin Urol 1986; 4: 217 ± 224. 5 Juenemann KP et al. Blood gas analysis in drug-induced penile coupled cAMP and cGMP second messenger sys- erection. Urol Int 1986; 41: 207 ± 211. tems. The larger size of the penis in cats, dogs, and 6 Lue TF et al. Hemodynamics of canine corpora cavernosa primates allows for more accurate and reproducible during erection. Urology 1984; 24: 347 ± 352.

International Journal of Impotence Research