Biomedical subjects

R M Levin

Publications and source records attributed to R M Levin.

At least 235 records · Page 13Linked to original sources

PubMed1990

Time-course of alterations of bladder function following acetone-induced cystitis.

Although chemical cystitis is known clinically to cause decreased bladder function, there are few experimental studies on the progression of, and recovery from chemical cystitis. Mature male rabbits underwent intravesical instillation of 50% acetone solution through a urethral catheter. Micturition profiles showed a marked decrease of the mean and maximal micturition volume and an increase in number of micturitions as early as one day after treatment. The micturition profile gradually normalized between four and eight weeks after instillation. In vivo cystometry showed a very small bladder capacity and low compliance during the first week following instillation, and gradually recovered to control levels by four weeks. Functional studies using the in vitro whole bladder model showed a significant decrease in the ability of the bladder to generate pressure and to empty at three days after instillation. These parameters recovered partially by two weeks, and completely by four weeks. Chemical cystitis induced by intravesical acetone instillation resulted in a severe decrease in the bladder function, i.e. contracted bladder with low compliance and poor ability to generate pressure and empty. However, these changes were reversible within the two month period of study.

Acetone↗

PubMed1990

Diagnosis of interstitial cystitis.

We reviewed clinical and histological findings in 55 patients with interstitial cystitis and 21 with voiding dysfunction secondary to other pathological conditions. Of our interstitial cystitis patients 36% would fail to meet the research definition proposed at a recent National Institutes of Health workshop. Detrusor mastocytosis was present in 64% of our interstitial cystitis patients compared to 80% of the noninterstitial cystitis group. There was no statistically significant difference in mean detrusor mast cell counts between interstitial cystitis and noninterstitial cystitis patients. Biopsies of 12 patients who did meet the proposed National Institutes of Health research definition were evaluated by immunohistochemical techniques. Early results are inconclusive. These studies indicate that interstitial cystitis is a complex disease whose diagnosis presently still must be made from a symptom complex rather than from objective histological criteria, including mastocytosis or the presence of any specific immunoreactive cell.

Cell Count↗

PubMed1990

The functional effects of long-term outlet obstruction on the rabbit urinary bladder.

The current study investigated the relationship between duration of outlet obstruction, magnitude of bladder mass, and functional dysfunction on the rabbit urinary bladder. Following the production of obstruction with the "cuff model", bladder wet weight increased to twice control weight within one week, and then slowly to four times control weight by one month, and remained at this level for the six month period. Bladder capacity decreased significantly by one week but returned to control volumes by one month. The in vitro ability of the bladder to empty in response to field stimulation and bethanechol decreased significantly in the one and two week obstructed bladders and remained decreased for six months. One of the major observations of this study was the relatively large variation of bladder weight and histology observed for the one to six month obstructed rabbits. Although the bladders with mild mass increase (less than 3 gm./kg. body weight) had normal distribution of urothelium and muscular elements, the bladders with moderate mass increase (3 to 6 gm./kg.) had thick extrinsic connective tissue deposits and the bladders with severe mass increase (greater than 6 gm./kg.) had thick extrinsic and intrinsic connective tissue deposits and muscular degeneration. The percentage occurrence of mild, moderate and severe mass increase was approximately the same (58%, 30% and 12%, respectively) for the one, three, and six month groups. The bladders with mild mass increase had normal bladder capacities and increased pressure responses to field stimulation and bethanechol. The bladders with moderate-to-severe mass increase showed enlarged bladder capacities and had progressively smaller pressure responses. As the magnitude of bladder mass increased, the ability of the bladder to empty in response to field stimulation and bethanechol decreased proportionally. We conclude that the functional impairment of the bladder is related to the amount of extrinsic and intrinsic connective tissue and the degree of muscle degeneration.

Adenosine Triphosphate↗

PubMed1990

Effects of outlet obstruction on glucose metabolism of the rabbit urinary bladder.

Bladder outlet obstruction has been shown to cause detrusor contractile dysfunction. To determine if alterations in bladder metabolism may in part underlie these functional defects, we investigated the effects of mild outlet obstruction on the glucose metabolism of the rabbit urinary bladder. Mild outlet obstruction was created in mature male rabbits by the surgical placement of a silicon sleeve around the bladder neck. Two weeks after surgery, the in vitro ability of the obstructed bladder tissues to metabolize glucose was compared to that of the controls. The results can be summarized as follows: 1) The bladder wet weight increased 2.3-fold following two weeks of obstruction. 2) Obstructed bladder tissues had a reduced glucose consumption as compared to the controls. 3) CO2 generation was significantly reduced by 31% in obstructed bladder tissues whereas lactate formation increased significantly by 22%. 4) Tissue concentrations of ATP, creatine phosphate, and glycogen before incubation showed no significant differences between control and obstructed bladder tissues. In summary, bladder tissues following two weeks obstruction showed a decrease in aerobic metabolism and an increase in anaerobic metabolism. Previous studies have indicated that the ability of the bladder to maintain a contraction and empty may be directly related to aerobic metabolism. Therefore, the decrease in aerobic metabolism (even in the presence of increased anaerobic metabolism) may in part explain the decreased ability of the obstructed bladder to empty.

Adenosine Triphosphate↗

PubMed1990

Comparative physiology and pharmacology of the cat and rabbit urinary bladder.

The cat and the rabbit are two of the most popular models for the study of lower urinary bladder function. The cat has been used extensively for in-vivo studies of spinal and supra-spinal micturition reflexes. In contrast, the rabbit has been used extensively for the in-vitro study of bladder function. In order to determine if the results obtained using one species can be applied to another, we have compared the in-vitro physiology and pharmacology of the cat and rabbit bladder using isolated strips and whole bladder preparations. The results can be summarized as follows: 1) The cat displays significant spontaneous activity during in-vitro cystometry, but the rabbit shows no such activity (whole bladder studies). 2) Although the bladder weights of the cat and rabbit are similar, the rabbit bladder has a capacity three times that of the cat. 3) The maximal response to field stimulation was obtained at one gram of passive tension for the rabbit isolated strips, whereas five grams of passive tension was required for the cat strips. 4) Atropine inhibited the response of isolated strips of cat bladder to field stimulation by approximately 13% whereas the response of rabbit bladder strips was inhibited by approximately 45%. 5) The magnitude of the response of rabbit bladder strips to ATP was similar to the response to field stimulation in the presence of atropine; the response of cat bladder strips to ATP was only 20% of the response of that of the rabbit bladder strips, and approximately 10% of the response of the cat strips to field stimulation in the presence of atropine. 6) Field stimulation produced a 10fold greater rise in intravesical pressure in the cat isolated bladder than in the isolated rabbit bladder; in response to bethanechol, the cat bladder generated a 6-fold greater response than the rabbit bladder. It is clear that the in-vitro pharmacological responses of the cat urinary bladder are qualitatively and quantitatively different from that of the rabbit bladder.

Adenosine Triphosphate↗

PubMed1990

Short term functional effects of bladder outlet obstruction in the cat.

Experimental bladder outlet obstruction in cats was produced by surgical placement of a silastic cuff around the urethra. Two sizes of cuff were used to produce either moderate or severe obstruction. The following is a summary of the short-term effects on bladder function. Obstruction induced a significant increase in the in vivo voiding pressure, in proportion to severity of the obstruction. There were no significant differences between control and obstructed cats in bladder mass, response of the isolated whole bladder to field stimulation or bethanechol, response of isolated bladder strips to field stimulation, bethanechol and ATP, or muscarinic receptor density in the bladder body. Although there were no differences in bladder mass between control and obstructed bladders, the hydroxyproline concentration of the severely obstructed bladders was significantly reduced. Creatine phosphate concentration was also significantly reduced in obstructed bladders. Although all whole cat bladder preparations displayed spontaneous contractile activity during in vitro cystometry, the obstructed bladders had a greater amplitude and frequency of spontaneous contractions with a lower volume threshold. In addition, the obstructed bladders had a greater tetrodotoxin-resistant contractile response to field stimulation. These results suggest that the obstructed cat bladder can compensate for increased outlet resistance without induction of bladder hypertrophy or significant functional changes, as seen in both rat and rabbit.

Adenosine Triphosphate↗

PubMed1990

Comparison of urinary bladder function in sexually mature and immature male and female rats.

Although studies exist using both male and female rats, there are virtually no studies that compare male and female bladder function. In this initial study, in-vivo and in-vitro urinary bladder function was investigated in two age groups of male and female rats (sexually immature and sexually mature). These studies compare in-vivo micturition behavior (water intake, urine output, frequency and volume per micturition); and in-vitro whole bladder function (bladder volume/pressure relationships, the ability of the in-vitro bladders to generate pressure and empty in response to bethanechol and field stimulation). The results can be summarized as follows: 1) The 24 hour water intake, urine output, and volume per micturition for the mature male rats was significantly greater than that of the mature females with no significant differences among the immature females, mature females, or immature males. 2) There were no significant differences in the frequency of micturition between the 4 groups. 3) Although the average plateau pressures (cystometrograms) of the immature and mature female bladders were greater than that of the immature and mature male bladders, the compliance was similar for all groups. 4) The maximum pressure response of the mature female bladder was significantly greater than pressures generated by bladders in the other three groups; there were no age or sex related differences in the bethanechol log ED50 values. 5) There were no age or sex-related differences in the bethanechol log ED50 values or maximal expulsion responses. 6) Field stimulated bladders from mature animals generated significantly greater intravesical pressures than bladders from immature animals, but, there were no significant differences in maximal pressures attained between mature male and female bladders nor between immature male and female bladders. In conclusion, micturition behavior, and the maximal pressure response to bethanechol changed dramatically with sexual maturity. These results are consistent with the idea that estrogen and other hormones may have a marked influence on bladder function and micturition behavior.

Animals↗

PubMed1990

Effect of magnesium chloride on rabbit bronchial smooth muscle.

STUDY OBJECTIVE: The objective of this study was to determine the extent to which magnesium relaxes bronchial smooth muscle during induced contraction. DESIGN: An in-vitro model using bronchial rings from New Zealand White rabbits stimulated to contract by electrical stimulation, histamine, or bethanechol. INTERVENTIONS: Magnesium chloride 1, 6, 16, 36, and 86 mM was added to each tissue bath and resting tension was measured. Electrical stimulation 100 V/100 ms, histamine 10 mM, or bethanechol 6.25 mM was added to washed tissues to induce contraction. This was followed with magnesium chloride 5, 10, and 50 mM, and the response of bronchial smooth muscle was measured. MEASUREMENTS AND MAIN RESULTS: Magnesium chloride 1, 6, 16, 36, and 86 mM decreased the mean +/- SEM resting tension of bronchial rings by 40 +/- 16, 100 +/- 11, 110 +/- 10, 170 +/- 9, and 275 +/- 22 mg, respectively. Electrical stimulation (4) of 100 V/100 ms increased the mean +/- SEM resting tension by 168 +/- 52 mg. Magnesium chloride 5, 15, and 50 mM added to the tissue bath decreased the response to 100 V/100 ms to 65 +/- 27, 40 +/- 23, and 1 +/- 0 mg, respectively. Histamine 10 mM (4) increased mean +/- SEM resting tension by 490 +/- 121 mg. Magnesium chloride 5, 15, and 50 mM decreased the histamine response by 80 +/- 56, 250 +/- 74, and 475 +/- 131 mg, respectively. Bethanechol 6.25 mM (14) increased the mean +/- SEM resting tension by 495 +/- 74 mg. Magnesium chloride (5, 15, 50 mM) decreased bethanechol-induced tension by 52 +/- 18, 184 +/- 26, and 506 +/- 64 mg, respectively. CONCLUSION: Magnesium chloride produced dose-dependent relaxation of bronchial smooth muscle at rest and when stimulated by histamine, bethanechol, or electrical impulse. Calcium chloride was unable to significantly reverse magnesium-induced relaxation. These data support the hypothesis that magnesium relaxes smooth muscle and dilates bronchial rings.

Animals↗

PubMed1990

Length-tension relationship of urinary bladder strips from streptozotocin-diabetic rats.

Streptozotocin-induced diabetes mellitus or the consumption of 5% sucrose in place of drinking water cause an increase in rat urinary bladder capacity and mass. Length-tension curves were generated using bladder body strips isolated from control, diabetic, or sucrose-drinking rats to determine whether the length-tension relationship was altered by the bladder hypertrophy associated with diabetic and nondiabetic diuresis. In addition, we compared the data using three different methods of expression: (1) absolute grams tension developed; (2) grams tension/100 mg tissue, and (3) grams tension/mm2. The cross-sectional area of strips from diabetic rats was increased compared to the other two groups. The length-passive tension curves for all three groups increased with increasing tissue length to a plateau. No optimal resting length for generation of active tension was found. Strips from diabetic and sucrose-drinking rats reached the plateau at a slightly larger passive tension than did strips from control rats. In addition, strips from diabetic and sucrose-drinking rats generally developed a greater active tension than did strips from control rats depending on the method of data presentation used. The data suggest that the complex nonlinear arrangement of smooth muscle fibers in the bladder wall results in the unusual length-tension curves generated by urinary bladder strips (as compared to skeletal or vascular smooth muscle). This relationship would be of benefit in the urinary bladders of early-stage diabetic patients before neuropathy development, where the stretching of the bladder wall would allow accommodation without any compromise of bladder function. The data indicate that comparisons of bladder strip function from control and diabetic rats should be done at passive tensions of greater than or equal to 2 g to ensure that maximal active tension is generated.

Animals↗

PubMed1990

Development factors in the contractile response of the rabbit bladder to both autonomic and non-autonomic agents.

Previous work in this laboratory has demonstrated that the bladders of 1-day-old and 1-week-old rabbits generate higher pressures in whole-bladder preparations than bladders from mature 8-week-old rabbits. In addition, the density of cholinergic receptors does not change during this maturation period. The present study was designed to determine if the increased responsiveness of the neonatal bladder was specific for cholinergic stimulation. Using bladder strips, we have demonstrated that the newborn bladders generated much greater tension in response to ATP, serotonin, histamine, and substance P. The response of the 1-day-old bladder smooth muscle to these contractile agents was at least double the response of the 8-week-old bladders. However, the response of all age groups to bethanechol was approximately the same, and the response to KCl was only 40% greater in the 1-day-old bladders as compared to the adult. These current studies indicate that the newborn bladder responds to a variety of nonadrenergic, noncholinergic agonists to a significantly higher degree than the adult bladder, and that maturation is accompanied by substantial changes in the pharmacology of the bladder.

Adenosine Triphosphate↗

PubMed1990

Effect of pregnancy on rabbit urinary bladder physiology. 1. Effects of extracellular calcium.

Recent advances in imaging technology have allowed for the diagnosis of many congenital urologic abnormalities through the use of antenatal ultrasonography. There is controversy in the literature as to whether antenatally detected dilatations of the urinary tract are always secondary to obstruction or if in select cases the dilatations are physiologic in nature and will spontaneously regress. Benign dilatations of the fetal urinary tract are postulated to be secondary to the increased fetal diuresis and a more compliant fetal urinary tract. No one has investigated the possibility that such dilatations might be a consequence of the hormonal changes seen with pregnancy. In this study we present evidence for a change in bladder function with pregnancy. A summary of our results shows that in the presence of bethanechol, strips from the urinary bladders of pregnant rabbits generate 50% less tension in response to calcium than those from nonpregnant rabbits. Such a suppression in smooth muscle function might also help explain the benign dilatations of the upper urinary tract which are seen frequently during pregnancy.

Animals↗

PubMed1989

Pharmacological responses of rabbit urinary bladder after subtotal cystectomy.

Partial cystectomy is used clinically in specific circumstances. There have been some reports indicating that the bladder following subtotal cystectomy can regenerate to a certain degree. The present study investigates the physiology and pharmacology of bladder regeneration at eight weeks after resection of a major part of the bladder body in rabbits. The following studies were performed on control and cystectomy bladders: 1) in vivo cystometry (prior to and four weeks after the operation, and before the sacrifice at eight weeks); 2) sequential muscle strip study (the strips were obtained by dividing bladder transversely into upper body, lower body, mid-bladder, upper base and lower base); and 3) in vitro whole bladder studies. The results can be summarized as follows: 1) grossly there was no regeneration of the bladder body; the cystometric capacity was increased slowly after the operation primarily due to increased size and capacity of the bladder base. 2) The contractile response of the subtotal cystectomized bladder body to field stimulation and bethanechol stimulation was less than the response of normal bladder body. 3) The contractile response to epinephrine showed that the ratio of alpha/beta adrenergic response was much greater in the cystectomy bladder than in the normal bladder. 4) In the whole bladder study, the intravesical pressure response to field stimulation was about the same in both groups, the response to bethanechol was less for cystectomized bladder, and the response to methoxamine was greater for the cystectomized bladder. 5) The ability of cystectomy bladder to empty in response to both field stimulation and bethanechol was impaired whereas the control bladder fully emptied to both field stimulation and bethanechol. In conclusion, over the eight week period following subtotal cystectomy the capacity increased via distention (and hypertrophy) of the bladder base area as opposed to regeneration of the bladder body.

Adenosine Triphosphate↗

PubMed1989

Functional and biochemical alterations in the rabbit urinary bladder following ileocystoplasty.

Although the use of ileocystoplasty has increased significantly in recent years, very little is known concerning the smooth muscle properties of the implanted bowel segment. In a previous study, preliminary evidence was presented which indicated that the pharmacological response of the cytoplastic ileal segment to autonomic agonists changed toward that of the bladder. The present study extends and expands these preliminary observations on the physiology and pharmacology of augmentation cystoplasty. Augmentation cystoplasty with detubularized ileum was carried out in 16 rabbits. In vivo and in vitro physiological and pharmacological studies were carried out one and three months after surgery. The results can be summarized as follows: 1) in-vivo CMG at one month was similar to that of the preoperative bladder, but at three months there was a 24% increase in capacity, with the presence of multiple phasic contractions beginning at a volume of approximately 65% of capacity. 2) The frequency and magnitude of spontaneous activity in the cystoplastic ileum did not significantly alter from that of the normal ileum. 3) Cystoplastic ileum responded to muscarinic stimulation differently from the normal ileum. The bladder responded with an increase in the tension whereas the ileum responded with an increase in the frequency and amplitude of phasic contractions. The cystoplastic ileum responded with a pronounced sustained contraction with phasic contractions superimposed. The tonic contraction at three months was of a significantly greater magnitude than that at one month. 4) The qualitative and quantitative response to field stimulation of the cystoplastic ileum was altered from that of the ileum towards that of the bladder. 5) The normal bladder contains greater amount of creatine phosphate and lesser amounts of creatine than the normal ileum. Cystoplasty, after three months induced a change in the ileal segment towards the bladder (increased creatine phosphate and decreased creatine). 6) The normal ileum was found to have greater number of muscarinic receptors than the normal bladder whereas the cystoplastic ileum at three months was intermediate.

Animals↗

PubMed1989

Effect of chronic ischemia on glucose metabolism of rabbit urinary bladder.

The effect of chronic ischemia on glucose metabolism of the rabbit urinary bladder was studied. Unilateral ischemia was produced by ligation of one of the two vesical arteries which supply the rabbit bladder. Two weeks after the operation, the in vitro glucose metabolism of normal bladder tissue was compared to the glucose metabolism of tissue isolated from both the ischemic side and contralateral (non-ischemic) side of the ischemic bladder. The results can be summarized as follows: 1) ischemic and contralateral side bladder tissues contained less glycogen than normal; 2) glucose utilization was higher in the ischemic and contralateral side tissues; 3) ischemic and contralateral side tissues incorporated more glucose into lactate and produced more total lactate than normal tissues; 4) whereas contralateral side tissue produced more 14CO2 than ischemic side tissue, the ability of normal bladder tissue to form 14CO2 is significantly higher than both ischemic and contralateral side tissues; 5) the degree of reduced CO2 production correlated well with previous studies on the contractile response of smooth muscle strips isolated from the ischemic and contralateral sides, and the reduced functional ability of the in vitro whole bladder to empty; 6) histologically, smooth muscle degeneration and necrosis is only present on the ischemic side of the bladder although the contralateral side shows signs of generalized degeneration and edema. In general, we conclude that although only the ischemic tissue demonstrated major smooth muscle degeneration and necrosis, unilateral ischemia resulted in marked alterations in glucose metabolism on both the ischemic and contralateral sides.

Animals↗

PubMed1989

Effect of acute complete obstruction on the rabbit urinary bladder.

Studies on the effect of partial bladder outlet obstruction demonstrate that significant alterations in urinary bladder structure and function occur within 24 hours of the creation of the obstruction. These studies suggest that many of the functional and structural alterations following partial outlet obstruction may result from the initial overdistension which occurs within the first 24 hours. In these present studies, we investigated the time course of the effect of complete obstruction of the rabbit urinary bladder on the contractile response to bethanechol and field stimulation and on the muscarinic receptor density. Male White New Zealand rabbits were divided into five groups: controls, four, eight, 20, and 24 hours of complete obstruction. The results demonstrated that there was a significant decrease in both the contractile response to muscarinic stimulation and muscarinic receptor density at four hours following outlet obstruction (at a time when there was no bladder overdistension). The receptor density and contractile response to stimulation further decreased over the 24 hour period. These studies indicate that the initial decrease in muscarinic receptor density and contractile response to muscarinic stimulation may be mediated in part by the high level of spontaneous contractile activity induced by ligation of the urethra.

Animals↗

PubMed1989

Effects of age on urinary bladder function in the male rat.

In a previous study we investigated the effects of age on the micturition characteristics and bladder function of male Fischer rats ages five to seven, 16 to 18 and 22 to 24 months. The 24 hr. water intake and urine output increases significantly with age; 22 to 24 month rats showed a 39% increase in water intake and a 93% increase in urine output compared to five to seven month rats. The intravesical pressure at micturition is 100% greater in 22 to 24 month and 16 to 18 month rats compared to five to seven month old rats with no age-related change in bladder volume at micturition. In the present study, in vitro bladder capacity did not differ between the three age groups although the average plateau pressure significantly decreased with advancing age. Using the isolated whole bladder model, the contractile response to the autonomic agonists bethanechol, phenylephrine, and isoproterenol did not change significantly with age. Similarly, there were no age-related changes in the response of the bladder to non-autonomic drugs (histamine, oxytocin, serotonin, substance P, and PGF2 alpha) except for PGF2 alpha which produced an age-related increase in the maximum bladder contraction. In summary, while in vivo micturition clearly changes with age, the in vitro contractility of the bladders to autonomic agents did not. Therefore, age related differences in micturition would be related primarily to the changes in neuronal innervation and central control of micturition rather than alterations in the contractility of the bladder. In addition, these studies show the importance of correlating in vivo bladder function (micturition frequency and volume, cystometry and urodynamics) with in vitro contractile and functional studies.

Aging↗

PubMed1989

Functional and pharmacological effects of ureteral diversion.

Urinary diversion is the final therapeutic approach in several bladder pathologies including selected cases of bladder cancer, neurogenic bladder, and painful bladder syndrome. While there have been a few experimental studies on the effects of urinary diversion and subsequent undiversion on bladder capacity, the pharmacological changes occurring with diversion and undiversion have not yet been investigated. Our primary objectives were to determine the functional and pharmacological alterations in the defunctionalized bladder and the effects of refunctionalization on these changes. Thirty-two male adult canines weighing 15 to 20 lb. were used for this study. Three groups of dogs were urine diverted for one, three, and six month durations (four dogs per group). Another three groups of dogs were urine diverted for one, three, and six months (four dogs per group); these dogs were then undiverted for three months. Six control animals received either one or two sham operations at one, three, and six months. In all groups the functional and contractile characteristics of the bladders were assessed by urodynamics and in vitro contractile studies; bladder weight and muscarinic receptor density were also measured. Intravesical capacities determined by in vivo cystometry were reduced significantly to 74%, 63%, and 47% of control values at one, three, and six months respectively after urinary diversion. Bladder capacity returned to above normal levels in bladders diverted and then subsequently undiverted. Similarly, the compliance and bladder weight of the diverted bladders were significantly less than control, while diverted bladders subsequently undiverted were similar to controls. Maximal bladder contractility in response to bethanechol stimulation was less in diverted bladders compared to control. This decrease in contractility was accompanied by a decrease in muscarinic receptor density. After undiversion maximal bladder contractility to bethanechol reached control levels; this was accompanied by a parallel increase in muscarinic receptor density to control values. There was no effect of diversion or undiversion on the maximal response of bladder strips to methoxamine stimulation. Thus, a bladder that has been diverted (defunctionalized) for a period of time showed decreases in capacity, compliance, and contractility to muscarinic stimulation along with a decrease in muscarinic receptor density. All of these parameters were restored after refunctionalization of the bladder.

Animals↗

PubMed1989

In vitro intravesical instillation of anticholinergic, antispasmodic and calcium blocking agents (rabbit whole bladder model).

The systemic side effects accompanying oral pharmacotherapy of neurogenic bladder dysfunction present significant drawbacks to this type of therapy. In these studies we investigated the effect of intravesical administration of anticholinergic, antispasmodic and calcium blocking agents on pressure response mediated by field stimulation and bethanechol. We used the rabbit in vitro whole bladder model for these experiments. The bladder from a mature male NZW rabbit was mounted in an organ bath as a whole bladder preparation. After control field stimulation and bethanechol stimulation, 20 ml. of saline containing the specific drug being evaluated was instilled into the bladder. At 30 minute intervals, the responses to field stimulation and bethanechol were determined. Two hours after instillation of 100 microM of each specific drug, the inhibition of the contractile response to bethanechol and field stimulation (as % inhibition) was as follows: oxybutynin (95%/64%), verapamil (85%/81%), atropine (68%/31%), diltiazem (47%/39%), and imipramine (44%/47%). Atropine and oxybutynin suppressed the contractile response of the bladder to bethanechol to a much greater extent than that to field stimulation, while verapamil, diltiazem and imipramine suppressed the contractile response to bethanechol and field stimulation to approximately the same extent. Two hours after drug instillation, the intravesical solution was washed out and replaced with saline, but the recovery of the bladder contraction was slow and incomplete. The results of this study suggest that the use of self-intravesical instillation to suppress bladder contractility should be a good therapeutic approach for patients with neurogenic bladder, especially those who are already managed by intermittent catheterization.

Administration, Intravesical↗