Studies of the pathophysiology of idiopathic detrusor instability: The physiological properties of the detrusor smooth muscle and its pattern of innervation

Purpose: Idiopathic detrusor instability (IDI) is a common cause of lower u rinary tract storage symptoms, such as urgency, frequency and urge incontin ence. We have investigated the in vitro properties and pattern of innervati on of the detrusor from patients with this condition. Materials and Methods: Full thickness bladder specimens were obtained perio peratively from 14 patients with IDI and from 14 cadaveric controls undergo ing 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 concentra tion response curves for carbachol (10(-7) M to 5 x 10(-4) M) and potassium (12 mM to 120 mM) were constructed. Acetylcholinesterase histochemistry an d immunohistochemistry for both phosphorylated and non-phosphorylated neuro filaments 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 per iod. 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 wer e 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). Mor phometric 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 abno rmality in IDI at the level of the bladder wall, with evidence of altered s pontaneous contractile activity consistent with an increased electrical cou pling of cells, a patchy denervation of the detrusor and a potassium supers ensitivity.