[Animal experiment, can we replace?] / Expérimentation animale, peut-on s'en passer ?

Animal experiment is a subject of controversies. Some people, defenders of animals, think that it is not acceptable to use for scientific purposes at the risk of making them suffer or assert that the results obtained with animals are not transposable in the human beings. Others, in particular researchers in biology or medicine, think that the animal models are essential for the biomedical search. This confrontation of the opinions bases largely on an evolution of the place of animals in our society. The regulations authorize the use of animals for scientific purposes but oblige to make it under restrictive conditions. The application of 3Rs - replacement, reduction, and refinement - expressed in 1959 by Russel and Burch is an ethical guide to improve the welfare of animals in research. The alternative methods do not allow, in the present state of the knowledge, to answer all the scientific questions in biology and medicine research. They are, most of the time, complementary methods of the in vivo methods.

Experimental study of urodynamic changes after ovariectomy in 10 dogs.

The urodynamic changes in 10 bitches up to 18 months after they had undergone ovariectomy were investigated. There were significant decreases in the maximum urethral closure pressure, the functional urethral length and the total integrated pressure profile 18 months after spaying, resulting in a caudal shift of the urethral profile, and a deterioration of urethral closure function. Each urethral pressure profile was divided into three equal sections; the mean cranial and middle integrated pressure decreased significantly and consistently over the 18-month observation period whereas the caudal integrated pressure increased.

Bladder response to urethral flow in the awake ewe.

The flowing of fluid along the urethra can facilitate the bladder micturition contraction, a reflex appropriate to achieve complete bladder emptying. The response has been observed in animals studied in the decerebrate, spinal, or anesthetized intact state but is difficult to demonstrate in awake, healthy humans. The aim of this study was to investigate this reflex in the awake, intact state using urodynamics in the ewe. The animals were fully awake and lay gently restrained on a recording table. The bladder was catheterized, and urethral flows were obtained by slowly injecting saline at the level of the proximal urethra. Bladder and rectal pressure were monitored, and the responses to urethral flow were tested at various bladder volumes. Urethral flows consistently evoked detrusor contractions in all animals. The response started approximately 2 seconds after the beginning of the flow and largely outlasted the stimulus. Its amplitude was similar to that of the bladder-to-bladder micturition reflex, and, like the latter, it always required some degree of bladder filling to appear. The reflex was selectively suppressed by local anesthesia of the urethral mucosa, indicating that the effect must originate from urethral receptors. Small urethral flows thus appear to elicit large bladder micturition contractions in awake healthy animals, and the reflex could be quite significant during the normal micturition. That this reflex is found in all studied species further supports the notion that the negative results in normal awake humans are owing to descending inhibitory controls rather than to the lack of appropriate pathways.

Urodynamic parameters in scrapie-affected ewes and their modifications in the course of the disease.

The aim of this study was to determine the urological abnormalities linked to spontaneous spongiform encephalopathy and their occurrence in the course of the disease. The animals used in this were 11 healthy and 20 scrapie-affected ewes. The scrapie-affected ewes were studied at a rate of once a month (1 to 5 measures; mean, 2.55) until they died. Urodynamic explorations were performed. The bladder activity was explored using cystometry. The urethral activity was measured during cystometry and during a urethral pressure profile. Both were analyzed using International Continence Society recommendations. Results showed in scrapie-affected ewes a decrease in functional bladder capacity and an increase in detrusor contraction incidence during filling of the bladder and in the occurrence of significant urethral instability. Bladder abnormalities were seen only in scrapie-affected ewes and worsened during the course of the disease. Urethral instability was not typical of the disease but was significantly more frequent in scrapie-affected ewes. It was concluded that lower urinary tract dysfunction occurred in scrapie-affected ewes and worsened during the course of the disease. This dysfunction is in agreement with overactive detrusor function due to neurological lesions.

Effects of metoclopramide on the urethral pressure profile of healthy dogs.

PURPOSE: The purpose of the present work was to study the effect of metoclopramide on urethral pressure since urethral relaxation is an important factor in vesical voiding. MATERIALS AND METHODS: Urethral pressure was measured in 6 dogs, anesthetized with propofol before and 1, 5 and 10 minutes after the administration of metoclopramide (0.5 mg/kg.) or placebo. RESULTS: A single injection of metoclopramide induced a large decrease in maximal urethral closure pressure (53 to 90%; mean 71%, p < 0.001--Anova). The decrease with placebo, 5 to 44% (mean 26%), was not significant (Anova test: p = 0.06). CONCLUSION: It is argued that a central dopaminergic action most probably accounts for this effect of metoclopramide on urethral pressure.

Comparative effects of xylazine and propofol on the urethral pressure profile of healthy dogs.

The effects of 2 drugs, xylazine and propofol, on the urethral pressure profile were compared. Seven female dogs were sedated by administration of one drug, then the other, and urethral variables were measured. In the dogs sedated with propofol, the mean +/- SD, maximal urethral closure pressure (51 +/- 7.4 cm of H2O) was significantly (P < 0.05) higher than the value when dogs were sedated with xylazine (23.3 +/- 7.6 cm of H2O). Results were compared with those obtained by various authors, in particular for nonsedated dogs. It is concluded that propofol is a good drug for investigation of the urethral pressure profile, whatever its effect on maximal urethral closure pressure.

Intra- vs intermuscular injections in swine.

In order to determine the exact localization (intra- vs intermuscular) in which a drug is injected when administered by a so-called intramuscular injection technique, a radiopaque test article (2 ml) was injected into the cervical musculature (2 sites), the loins and the gluteal mass in anaesthesized pigs. Immediately after this, the pigs were euthanized and deep-frozen. Then they were cut into slices, which were X-rayed to determine the exact localization of the test material. Semi-quantitative scores were given to each injection site according to the amount of test article found in or out of muscle mass and also to the absence or the presence of test article subcutaneously. The loins area obtained the highest score for intramuscular location, but in this site, injections were almost always followed by a flowing back of the test article to the subcutaneous' area. It was shown that an injection in the neck perpendicular to the skin surface just behind the base of the ear was the most appropriate site for intramuscular injection in pigs.

[Effect of vasopressin on the motor profile of the reticulum and rumen in sheep]. / Effets de la vasopressine sur le profil moteur du réticulo-rumen chez le mouton.

Intravenous injections of lysine-vasopressin into sheep inhibited rumino-reticular phasic contractions and electric activity. Sometimes, a rapid electric pattern was observed and persisted even after reappearance of normal phasic contractions.