The contribution of cholinergic detrusor excitation in a pig model of bladder hypocompliance.
OBJECTIVE
To investigate the role of cholinergic excitation in mediating changes in detrusor compliance (manifested on conventional cystometry as an incremental rise in detrusor pressure as bladder volume increases) under conditions of propofol-sedation in the pig. Materials and methods Consecutive cystometrograms (CMGs) were obtained from eight female Large White pigs at a bladder filling rate of 50 mL/min. The first CMG was obtained while the pig was awake and unsedated. Two subsequent CMGs were obtained after light to moderate sedation with propofol (2-8 mg/kg/h) before and after the administration of intravenous atropine (0.02 mg/kg).


RESULTS
All bladders were highly compliant over the volumes instilled (before sedation) with a maximum pressure during the filling phase of 0.9 cmH2O and a compliance of 943 mL/cmH2O. After sedation with propofol, the maximum pressure during the filling phase increased to 14 cmH2O with a compliance of 69 mL/cmH2O. Atropine antagonized this change in compliance; after sedation and atropine, the maximum pressure during the filling phase decreased to 4 cmH2O (P < 0.05) and the compliance increased to 337 mL/cmH2O (P < 0.05).


CONCLUSIONS
The decrease in compliance seen in the pig bladder after sedation with propofol is mediated via muscarinic excitation. This probably occurs as a result of low-level tonic release of acetylcholine by the efferent parasympathetic nerves. The existence of such efferent excitatory activity during the storage phase in the overactive human bladder might explain the efficacy of bladder-selective muscarinic antagonists in a proportion of patients with detrusor hyper-reflexia and instability.
Mills
I W
IW
Oxford Continence Group, University Department of Pharmacology, Mansfield Road, Oxford, UK.
Drake
M J
MJ
Greenland
J E
JE
Noble
J G
JG
Brading
A F
AF
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003187:Compliance; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011312:Pressure; D015742:Propofol / Q000494:pharmacology; D013552:Swine; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
D006993:Hypnotics and Sedatives; D018727:Muscarinic Antagonists; D001285:Atropine; D015742:Propofol