Studies of the pathophysiology of idiopathic detrusor instability: the physiological properties of the detrusor smooth muscle and its pattern of innervation.
OBJECTIVE
Idiopathic detrusor instability (IDI) is a common cause of lower urinary tract storage symptoms, such as urgency, frequency and urge incontinence. We have investigated the in vitro properties and pattern of innervation of the detrusor from patients with this condition.


METHODS
Full thickness bladder specimens were obtained perioperatively from 14 patients with IDI and from 14 cadaveric controls undergoing transplant organ retrieval. Isolated detrusor smooth muscle strips were mounted in organ baths for isometric tension recording. Frequency-response curves to electrical field stimulation (EFS) (1 Hz to 50 Hz) and concentration response curves for carbachol (10(-7) M to 5 x 10(-4) M) and potassium (12 mM to 120 mM) were constructed. Acetylcholinesterase histochemistry and immunohistochemistry for both phosphorylated and non-phosphorylated neurofilaments was carried out on frozen sections of control and IDI bladders.


RESULTS
IDI strips developed greater spontaneous tone (0.25 gm./mg. versus 0.12 gm./mg.; p <0.0001) and more spontaneous fused tetanic contractions (16.8% versus 6.8%; p <0.005) during an initial 90 minutes equilibration period. The IDI strips were less responsive than controls to nerve stimulation (max. response to EFS 0.79 gm./mg. versus 1.23 gm./mg.; p <0.0001) and were supersensitive to potassium (EC50 39.7 mM versus 45.7 mM; p = 0.003) but not to carbachol (EC50 7.3 x 10(-6) M versus 6.6 x 10(-6) M; p = 0.48). Morphometric studies revealed reduced staining of presumed cholinergic nerves, with 34.7% of IDI smooth muscle bundles appearing denervated compared with 1.5% of controls (p <0.0001).


CONCLUSIONS
Our study supports the notion that there is a fundamental abnormality in IDI at the level of the bladder wall, with evidence of altered spontaneous contractile activity consistent with an increased electrical coupling of cells, a patchy denervation of the detrusor and a potassium supersensitivity.
Mills
I W
IW
University Department of Pharmacology, Oxford, United Kingdom.
Greenland
J E
JE
McMurray
G
G
McCoy
R
R
Ho
K M
KM
Noble
J G
JG
Brading
A F
AF
D000328:Adult; D000368:Aged; D001285:Atropine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000294:innervation / Q000473:pathology / Q000503:physiopathology*; D011188:Potassium / Q000494:pharmacology; D001743:Urinary Bladder / Q000294:innervation / Q000473:pathology / Q000503:physiopathology*; D014555:Urination Disorders / Q000473:pathology / Q000503:physiopathology*
D001285:Atropine; D011188:Potassium