Children born with congenital bladder anomalies undergo abnormal bladder development. They often need multiple reconstructive surgery to improve bladder capacity, empyting, continence and to protect the upper urinary tract. Despite this these children continue to display symptoms of urinary incontinence, frequency, and urinary tract infection (Gearhart & Jeffs, 1998). Abnormal connective tissue and poor detrusor smooth muscle function have both been implicated (Thiruchelvam et al. 2003). The contractile properties of detrusor muscle in this population are unknown. We aimed to examine them the in vitro using human paediatric detrusor from normal patients and those with congenital bladder anomalies. Pathological bladder conditions included children with neuropathic bladder, bladder exstrophy and cloacal exstrophy. Full thickness bladder samples were obtained during open surgery. Normal tissue was obtained from those with urachal anomalies or those undergoing ureteric reimplantation. Detrusor strips (≈1mm diameter) were superfused at 37°C with a HCO3–/CO2 buffered physiological solution. Nerve-mediated responses were elicited by electrical field stimulation (1-60Hz, sensitive to 1µM tetrodotoxin) in the absence and presence of 10µM atropine. Agonist-induced responses were generated by carbachol (0.1-30µM) and α,βmethylene-ATP (ABMA 1µM). Tension was normalised to unit cross-sectional area (mN mm-2). Data are mean±s.d. and significance of differences (p<0.05) between sets were examined by Student’s t test. Nerve-mediated contractions were significantly less in samples from patients with pathological bladders compared to normals. The estimated maximum tensions from force-frequency plots were 1.8±3.1mN mm-2 and 8.1±8.7mN (n=52,18, pathology vs normal). The frequency required to generate half-maximum tension was not different in the pathological state (15.1±11.0 vs 17.8±10.5Hz, respectively). Atropine-resistant contractions were recorded in all preparations but they were a significantly greater proportion of total nerve-mediated responses in the normal group. Contractile responses to carbachol and ABMA were also significantly less in the pathological group. For carbachol the tension at the highest concentrations from dose-response curves were 6.8±7.0 vs 30.9±22.2mN mm-2, respectively. The carbachol EC50 was reduced in the pathological group (EC50s; 1.8±1.6 vs 3.2±1.2, n=45,16, respectively). Responses to 1µM ABMA were 1.5±2.1 vs 11.2±8.3mN mm-2, respectively. The data shows that detrusor from patients with pathological bladders exhibited reduced contractility, whether elicited by excitatory nerves or agonists. This was offset by an increase in the sensitivity to carbachol in the pathological group.
University College London 2006 (2006) Proc Physiol Soc 3, PC115
Poster Communications: The contractile properties of human paediatric detrusor smooth muscle in congenital bladder anomalies
Navroop Johal1, Peter Cuckow1, Christopher Fry1
1. Institute of Urology, London, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.