Correlation between the structure and function of the rabbit urinary bladder following partial outlet obstruction

Purpose: To understand the relationship between contractile and structural changes in the obstructed bladder, rabbit bladder was partially obstructed for up to 70 days and alterations in tension response to field stimulation and carbachol were compared with alterations in ultrastructure and innervat ion of detrusor smooth muscle (SM). The effect of partial outlet obstructio n on the physiological responses to field stimulation (FS) (nerve mediated contraction) and carbachol (receptor mediated contraction) mere correlated with the structure and innervation of the detrusor smooth muscle (SM) of th e same animal during a 70 day period. Materials and Methods: 28 rabbits were subjected to 1 to 70 days of mild pa rtial outlet obstruction. Sham operated rabbits were euthanized at 7, 14, 2 8, and 70 days post-obstruction. At each time period, isolated strips of bl adder body were mounted in individual baths and the contractile response to FS and carbachol determined. Three additional strips from each bladder wer e fixed for electron microscopy. Results: Bladder mass increased rapidly during the first 7 days after obstr uction, was constant for the next 7 days, and then continued to increase gr adually. Dysfunction of the contractile response to FS was noted as early a s 3 days and progressively increased over the 70-day study period. The decr ease in the response to FS increased at a significantly faster rate than th e decrease in the contractile response to carbachol. In ultrastructure stud ies, at 3 and 7 days post-obstruction the majority of SM cells displayed th e characteristics of hypertrophy. At 28 days some SM cells displayed loosel y packed myofilaments and an irregular distribution of sarcoplasmic dense b odies. At 70 days swollen mitochondria were present in all cell types of th e bladder wall. Evidence of axonal degeneration was first observed at 7 day s post-obstruction and became more extensive thereafter. No evidence of mit otic figures, nerve growth cones or regenerating SM cells was observed. Conclusions: Prolonged partial bladder outflow obstruction is accompanied b y a progressive decrease in contractility of SM. The present study describe s the structural damage that occurs in the bladder wall in response to part ial outlet obstruction and correlates these observations with the contracti le dysfunction with which it is associated. Furthermore, mitochondrial dama ge in vessels and fibroblasts is suggestive of bladder wall ischemia.