The underlying pathophysiological mechanism of urinary incontinence after spaying is a reduced closure pressure of the urethra, known as "urethral sphincter mechanism incompetence" (USMI). Within one year after spaying the urethral closure pressure is significantly reduced. Because many bitches only become incontinent years after surgery it took a long time until spaying was considered to be the cause. In one study, 83 (=20%) of 412 bitches, incontinence occurred 3 to 10 years after surgery (1).
The medical treatment of USMI is the method of choice and should always precede a surgical therapy. The action of the used substances implies an increase of the urethral closure pressure. In the first line alpha-adrenergic agonists are used. The effect of these sympathomimetic drugs is explained by the fact, that 50% of the urethral closure pressure is generated by the sympathetic nervous system. Alpha-adrenergic agonists improve the urethral closure pressure by stimulation of the alpha-receptors of the smooth urethral musculature (2-7). The treatment with alpha-adrenergic agonists results in continence in 75% of incontinent bitches.
An alternative is the treatment with estrogens, which is successful in 65% (1,8,9). But with estrogens unwanted side effects can occur such as swelling of the vulva and attractiveness for male dogs (8). Nowadays only short-acting estrogens (Estriol, Incurin®, Intervet, Netherlands) are used (10). The depot preparations used in the past are obsolete, in part because they can potentially cause a bone narrow depression (11). Estrogens indirectly increase the urethral closure pressure; they sensitize the alpha-receptors for endogenous and exogenous catecholamines (12). If therapy with alpha-adrenergic agonists is unsatisfactory, a combination with estrogens may potentiate the effect.
The alpha-receptors are divided in alpha1- and alpha2-subtypes. These receptor subtypes are distributed differently in each single effector. Alpha-1 receptors are found in many target organs of the sympathetic nervous system. With a few exceptions, alpha-2 receptors are not present in target organs of the sympathetic nervous system, but in neuronal synapses. It is now known, that the alpha-receptors at the bladder neck and proximal urethra of the bitch, which are responsible for continence, belong to the subtype 1 (13).
The side effects of alpha-adrenergic agonists is explained by the fact that alpha-1 receptors are not just found at the bladder neck, but also in other organs, especially in the wall of blood vessels. Phenylpropanolamine (PPA) acts selectively on alpha-1 receptors.
The older substance Ephedrine is less selective than PPA. It also stimulates beta-receptors and therefore has the tendency to have more side effects (2,3). In contrast to PPA a habituation to Ephedrine occurs. Because of these reasons PPA is the therapy of first choice.
In humans treatment with PPA sometimes causes side effects, such as an increase in blood pressure and headache. It may occasionally trigger a stroke or a heart attack and is therefore no longer used. With PPA used in dogs, at the recommended dose of 1.5 mg/Kg BW bid or tid, an increase in blood pressure was not observed (5, 14). The side effects observed in dogs were never life threatening and usually were self-limiting; diarrhoea, vomiting, anorexia, apathy, nervousness and aggressiveness (1,7,15).
For refractory cases different surgical therapies are available, of which colposuspension (16), urethropexy (17) and the endoscopic injection of collagen (18) are mainly used, with a success rate of 50-75%. With all three techniques a deterioration in the response rate was seen over time. At our clinic, we prefer the endoscopic injection of collagen as this method is least invasive, with a minimal rate of complications and the results are as good as the more invasive techniques.
References
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