Normal detrusor is more sensitive than hypertrophied detrusor to in vitro ischemia followed by re-oxygenation

Partial outlet obstruction results in marked metabolic as well as contracti le alterations. Specifically, the ratio of anaerobic to oxidative metabolis m is significantly greater in hypertrophied than normal bladder smooth musc le, lactate dehydrogenase (LDH) and lactic acid production an increased, an d the contractile apparatus is altered to allow for metabolically more effi cient tension generation. In addition, contractile responses of hypertrophi ed bladder are apparently more resistant than those of normal bladder to hy poxia. In the current experiment, we studied the effects of in vitro ischem ia (hypoxia + substrate deprivation) followed by an in vitro model of reper fusion (re-oxygenation + substrate replacement) on contractile responses of normal and hypertrophied urinary bladder strips. We used repetitive field stimulation (FS) during the hypoxic period as a model for hyperreflexia. Th e purpose of the current study was to compare the responses of normal and h ypertrophied bladder smooth muscle to repetitive stimulation in the presenc e of in vitro ischemia followed by re-oxygenation and substrate replacement . Thirty-two rats were separated into four groups of eight each. The rats i n groups 1 and 3 were subjected to partial outlet obstruction. Two weeks la ter, all rats were anesthetized; their bladders were isolated and cut into four strips. Each strip was mounted in an isolated bath, and after 1-hour i ncubation in Tyrode's solution containing glucose tin the presence of O-2), contractile responses to FS, carbachol, and KCI were determined. After thi s first set of stimulations, the strips were incubated without glucose and in the presence of N-2 for 30 minutes and 1 hour (groups 1 and 2); and for 2 and 4 hours (groups 3 and 4). For groups 1 and 2, the tissues were stimul ated at 5-minute intervals with FS at 32 Hz, I-millisecond duration, 3-seco nd trains tin vitro model of hyperreflexia). For groups 3 and 4, no stimula tions were performed during the ischemic period. At the end of the ischemic period, all strips were washed and incubated for I hour in the presence of O-2 and with glucose. At the end of this incubation, all strips received a second set of stimulations. a) Partial outlet obstruction resulted in a si gnificant increase in bladder weight. b) Responses to in vitro ischemia: Af ter in vitro ischemia, contractile responses of both normal and hypertrophi ed tissues to FS were reduced to a significantly greater degree than were r esponses to carbachol and KCl. The rate of development of contractile dysfu nction was significantly greater in normal bladder tissue strips than in hy pertrophied bladder strips. c) Responses to repetitive stimulation: The rat e of development of contractile dysfunction was significantly greater in al l strips subjected to repetitive stimulation than in those not repetitively stimulated; in addition, normal bladder strips were more sensitive than hy pertrophied strips to hypoxia and substrate deprivation-induced contractile dysfunction. The rate of contractile failure induced by in vitro ischemia followed by re -oxygenation and substrate replacement was significantly greater for normal bladder strips than for hypertrophied bladder strips. These results indica te that, after partial outlet obstruction, the hypertrophied tissue is more resistant than normal tissue to hypoxia and substrate deprivation. (C) 200 0 Wiley-Liss, Inc.