Bladder augmentation or substitution with bowel segments are surgical procedures intended to provide a high capacity, low pressure urine reservoir for patients with small, hypertrophied, low compliance, high pressure bladders. Preliminary studies have indicated that experimental, ileocystoplasty in rabbits shifts the muscarinic, alpha adrenergic and purinergic response of the ileum towards that of the bladder. This effect is important as a manifestation of the functional plasticity of visceral smooth muscle. The major goal of the proposed studies is to determine what physiological signal or signals induce this change. Of the many possibilities, 5 of the most obvious are: 1)- the different environmental input (i.e. periodic inflation and deflation), 2) exposure to urine, 3) reinnervation of the intestinal segment by bladder nerves, 4) overgrowth of intestinal muscle by bladder muscle, and 5) replacement of intestinal muscle by newly formed bladder muscle. The initial approach will be to compare cystoplasty with alternative surgical models which include: 1) Cystoplasty with and without continence, 2) Tubular vs. detubulirized cystoplasty, 3) Ileal pouch with and without periodic filling (with either saline or urine). By comparing the contractile pharmacology of ileal segments from the above models, it will be determined whether the observed smooth muscle plasticity is related to the filling cycle of the bladder, the presence of urine, physical contact with gladder muscle, or a combination of factors. The long term objectives are to understand the mechanism whereby intestinal smooth muscle becomes similar to bladder smooth muscle following cytoplasty. Armed with this knowledge, novel treatment strategies will be developed which may induce the neoreservoir to perform the bladder emptying function thus avoiding complications that intermittent catheterization imposes. In addition, these studies will provide a significant contribution to understanding the functional plasticity of visceral smooth mechanisms of smooth muscle and could lead to insights into mechanisms of smooth muscle excitation contraction coupling.
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