Oral nitric oxide donors: a new pharmacological approach to detrusor-sphincter dyssynergia in spinal cord injured patients?
OBJECTIVE
Detrusor-sphincter dyssynergia is a common cause of bladder outlet obstruction in spinal cord injured patients and leads to poor bladder emptying and high bladder pressures, which if left untreated might cause renal failure. In this study, we tested the recently published hypothesis that oral administration of a nitric oxide donor could be a new pharmacological approach to treat detrusor-sphincter dyssynergia in humans with spinal cord injury.


METHODS
12 male spinal cord injured patients presenting with neurogenic detrusor overactivity and detrusor-sphincter dyssynergia were studied. 6 performed clean intermittent catheterisation and 6 used suprapubic tapping for bladder emptying. During cystometry the bladder was filled until the first overactive bladder contraction accompanied by detrusor-sphincter dyssynergia occurred while bladder and external urethral sphincter pressures were continuously recorded. Then the bladder was emptied and the patients received 10 mg of isosorbide dinitrate sublingually. Resting pressures were recorded and cystometry was repeated starting 15 min after drug administration. Maximal and mean values for bladder and external urethral sphincter pressures were calculated in both fillings and statistically compared by analysis of variance for repeated measurements (level of significance p < 0.05).


RESULTS
Nitric oxide significantly reduced external urethral sphincter pressures at rest (p < 0.05) and during dyssynergic contraction (p < 0.05) while bladder pressures at rest and during contraction as well as the reflex volume remained unchanged. In the patients who used suprapubic tapping for bladder emptying the mean post triggering residual volume was significantly reduced (p < 0.05).


CONCLUSIONS
Oral administration of nitric oxide donors significantly reduced bladder outlet obstruction due to detrusor-sphincter dyssynergia suggesting a role for nitric oxide in inhibitory neurotransmission to the urethral sphincter. This new approach could offer a potential pharmacological option to treat detrusor-sphincter dyssynergia in spinal cord injured patients.
Reitz
André
A
Neuro-Urology, Swiss Paraplegic Center, Balgrist University Hospital, Forchstrasse 340, 8008 Zurich, Switzerland. areitz@balgrist.unizh.ch
Knapp
Peter A
PA
Müntener
Michael
M
Schurch
Brigitte
B
D000284:Administration, Oral; D000328:Adult; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage*; D008297:Male; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D013119:Spinal Cord Injuries / Q000150:complications; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy* / Q000209:etiology
D020030:Nitric Oxide Donors; D007548:Isosorbide Dinitrate