Proceedings of The Physiological Society

Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, PC138

Poster Communications

The use of inert bulking agents to reduce pig bladder spontaneous contraction

D. G. Kitney1,2, R. Jabr1, C. H. Fry2

1. Biochemistry and Physiology, University of Surrey, Bristol, United Kingdom. 2. Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom.

Spontaneous contractions of the bladder wall, enhanced in patients with overactive bladder (OAB), are abolished by removal of mucosa that overlies detrusor smooth muscle and a potential source of diffusible contractile mediators. Minimising communication between bladder layers may therefore reduce spontaneous activity and one approach is to inject inert bulking agents below the mucosa. We tested the hypothesis that 'inert injectables reduced spontaneous bladder contractions'. Pig bladders from a local abattoir were stored in fresh Tyrode's solution. Intact bladder wall segments (1x2cm) were dissected and superfused with Tyrode's solution (37oC). One end of the preparation was clamped to an anchor and the other to an isometric force transducer. Strips were exposed to 1µM carbachol (CCh, muscarinic agonist) or 0.3µM α,β-methylene ATP (ABMA, purinergic desensitiser) for 10min. Spontaneous contractions were measured before and during drug interventions. Preparations were then injected below the mucosa with polyethylene glycol (PEG) or coaptite (CA, 0.2 ml), or no material (null injectate) and drug exposure repeated. Data were analysed with a purpose-made algorithm and normalised to values before injections (control). For CCh and ABMA responses, contraction amplitude was measured. For spontaneous contractions, amplitude, force integral, and frequency, were all measured over a 10min period. Data sets are medians [25, 75% interquartiles] and compared using Mann-Whitney U-tests against the control. The null hypothesis was rejected at p<0.05. Time-dependent increases of CCh and ABMA contractions were recorded - null injection vs control (CCh: 156.2 [126.2, 250.8]%,n=11; ABMA: 142.3 [133.9, 224.9]%, n=11). This increase was abolished with PEG but not by CA injection. For CCh contractions: PEG 119.6 [102.6, 130.0]%,n=11; CA, 133.2 [118.1, 216.6]%,n=10. For ABMA contractions: PEG 99.4 [66.1, 109.0]%; CA, 139.7 [89.2, 228.7]%. Spontaneous contractions also changed in a time-dependent way (null injection vs control): Contraction amplitude increased significantly (172.3 [79.5, 304.5]%) as did force integral (128.6 [65.2, 228.4]%), but frequency was unchanged (106.7 [83.7, 134.0]%)(n=10). With PEG injection time-dependent changes were abolished: amplitude (109.4 [47.5, 115.4]%); frequency (113.7 [92.3, 150.2]%); force integral (68.6 [41.9, 127.2]%)(n=9). CA even reduced spontaneous contraction amplitude (77.0 [21.2, 112.5]%) and force integral (55.7 [17.7, 92.9]%), although frequency was slightly increased (133.3 [123.9, 161.3]%, n=9). Bladder spontaneous contractions are reduced by inert bulking agents, with coaptite more successful than PEG. This approach offers an alternative approach to pharmacological therapeutics in reducing symptoms of OAB.

Where applicable, experiments conform with Society ethical requirements