Bladder outlet obstruction can produce significant clinical voiding dysfunction which may persist after surgical relief of obstruction and, in some cases, be irreversible. Information regarding the effects of obstruction and the influence of timing of relief of obstruction may become important in decision-making policy related to clinical urologic practices and public health policy where clinical trials, outcome analysis and quality of life are involved. Clinical and experimental data regarding the effects of obstruction on bladder function has been steadily accumulating. However, there has been very little information about changes in electrical properties underlying changes related to obstruction. The proposal requests support to utilize a recently developed guinea pig model of urethral obstruction to study these electrical changes. During the period of the previous grant, we have constructed and equipped a laboratory of the study of urinary track smooth muscle in a clinical urology department. We have developed an animal model of gradual partial urethral obstruction using the guinea pig to study functional and structural bladder changes. In addition to studying the effect of obstruction and its release on in vivo urodynamic parameters, bladder weight, bladder muscle force development, cholinergic nerve content and collagen content, the model has permitted the first successful intracellular electrophysiological studies of passive electrical properties of obstructed bladder muscle. The present proposal is for the study of changes in passive and active electrical membrane properties occurring after obstruction and its release in a guinea pig model. Studies planned include measurement of resting membrane potential, length constant, time constant, changes in action potential and muscarinic and non-adrenergic, non-cholinergic neuromuscular transmission. Correlation with other functional and structural changes will be performed. The long term goal of the project is to produce a comprehensive description of the effects of obstruction and its release on the functional and structural properties of the urinary bladder in a single mammalian model.
