Urodynamic action of clonidine in the chronic spinal cat

Abstract

Spinalization produces a central micturition dysreflexia characterized by weak vesical contraction reflexes and by an exaggerated urethro-urethral contraction reflex, causing the peripheral syndromes of underactive detrusor and detrusor-sphincter dys-synergia. We explored the action of catecholaminergic drugs of central action on these micturitional dysfunctions.Twenty-four male cats were spinalized by transection of the spinal cord at C S C 6 level and studied 1-18 weeks later. Cystosphincterograms were performed without using anesthetic drugs. Pves, Pura, the EMG of the external sphincter, the EMG of the extensor hindleg muscles, and urine emission were studied. The responses of the spinal vesicovesical contraction, urethro-vesical contraction, and urethro-urethral contraction reflexes were explored. Clonidine (0.02-0.06 mg/kg intravenously [IV] , intraperitoneally [IP], or per os), phentolamine (0.7-1 mg/kg, IV), and yohimbine (0.4-1 mg/kg, IV) were administered.Clonidine, at doses of 0.02 mg/kg, IV or IP, or higher, produced the following effects: (1) it significantly increased the intensity and duration of Pves waves; (2) it inhibited the spasms of the external sphincter; (3) it induced voiding; (4) it reduced spasticity; (5) it reinforced the vesico-vesical contraction reflex; (6) it antagonized the exaggeration of the urethro-urethral contraction reflex; (7) it corrected totally or partially the underactive detrusor and detrusor-sphincter dys-synergia. Taken orally (0.02-0.03 mg/kg) the urodynamic effect of clonidine was not significant; higher doses produced vomiting and other adverse effects. The action of clonidine was blocked by yohimbine but not by phentolamine.These results suggest that the absence of the descending noradrenergic pathways plays a role in the physiopathology of neurogenic bladder dysfunctions in chronic spinalized cats.

Neural Control of the Lower Urinary Tract

“…In paraplegic patients, intrathecal injection of clonidine suppresses DO (181). Conversely, in conscious spinal cats, clonidine, an α 2 -adrenergic agonist, increases bladder pressures and facilitates voiding (225). …”

New Insights into the Pathophysiology of Detrusor-Sphincter Dyssynergia

“…Of note, the cats that exhibited phasic EUS activity showed no overt evidence of chloralose-induced smooth muscle dyssynergia or dramatic EUS activity decrement. A review of the literature examining LUT function in unanesthetized cats (decerebrate spinal cord intact and chronic SCT) supports the idea that micturition in this species is also characterized by micturition-associated phasic EUS activity [32][33][34][35][36]. That it is also apparent in SCT cats adds this species to the list of those that possess a spinal PFPAPG.…”

“…Cats also appear to have a true spinal micturition reflex [33,34,42], and the NVPMCs of SCT cats are also vanilloid sensitive [42], as in the rat. However, unlike the rat, there does seem to be vanilloid sensitivity to the spinal micturition reflex as well following SCT, suggesting that the reflex in SCT animals has a stronger C-fiber component.…”

“…That the species specifics of the frequency of micturition-associated phasic EUS contractions and the timing of these contractions in relation to the phase of the bladder contraction pressure wave may differ in specific details likely reflects allometric considerations and anatomic design differences [14]. For example, the hamster [22], rabbit [25], and cat [32][33][34][35][36] seem to favor phasic firing more toward the end of voiding, while the rat reliably demonstrates this activity throughout the voiding phase (unpublished observations). That in some species these micturitionassociated phasic EUS contractions appear obligatory for efficient voiding, while in others, they may be conditional does detract from the significance of the presence of this retained PFPAPG neural circuitry that drives them.…”

Neural Control of the Lower Urinary Tract

“…In paraplegic patients, intrathecal injection of clonidine suppresses DO (181). Conversely, in conscious spinal cats, clonidine, an α 2 -adrenergic agonist, increases bladder pressures and facilitates voiding (225).…”