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Biomedical subjects

Catherine Whitbeck

Publications and source records attributed to Catherine Whitbeck.

At least 19 recordsLinked to original sources

Effect of bilateral in vivo ischemia/reperfusion on the activities of superoxide dismutase and catalase: response to a standardized grape suspension.

PURPOSE: Ischemia/reperfusion (I/R) is a major etiological factor in the bladder dysfunctions observed in men with lower tract obstruction, women with postmenopausal incontinence and with aging. A standardized grape suspension protects the rabbit urinary bladder from both the contractile dysfunctions and the morphologic changes mediated by I/R. Using a model of in vivo bilateral ischemia/reperfusion, the current study investigated the effect of this grape suspension on the endogenous antioxidant defense systems. MATERIALS AND METHODS: 24 NZW rabbits were separated into 6 groups of 4. Groups 1-3 were treated by gavage with aqueous grape suspensions; groups 4-6 received sugar-water vehicle. Groups 3 and 6 were controls. Groups 1 and 4 were subjected to bilateral ischemia for 2 h (I). Groups 2 and 5 underwent bilateral ischemia for 2 h and reperfusion for 1 week (I/R). For all rabbit bladders, the muscle and mucosa were separated by blunt dissection and analyzed separately. The effects of the various treatments on bladder antioxidant systems of cytoplasmic superoxide dismutase (Cu-Zn superoxide dismutase; SOD), and catalase (CAT) were evaluated. RESULTS: The standardized grape suspension up-regulated both SOD and CAT activity of bladder muscle and mucosa in control animals. There were few differences in the grape suspension treated animals after ischemia, and in general the activities decreased following I/R. CONCLUSIONS: Increases of SOD and CAT activity in control animals as a result of grape suspension suggest a greater antioxidant capacity. This increase in the antioxidant defense system may explain the increased protection of grape suspension in the face of ischemia and I/R. However, the activities of both enzyme systems decreased in the smooth muscle subjected to I/R showing that reperfusion damages these systems probably via oxidation damage to the enzymes themselves.

Animals↗

The effects of cyclical oestrogen on bladder and urethral structure and function.

OBJECTIVE: To determine the effects of cycling oestrogen in rabbits, as oestrogen is essential for physiological maintenance and integrity of the female urogenital tract. MATERIALS AND METHODS: Changes in circulating oestrogen have marked effects on the bladder of experimental animals, with ovariectomy (Ovx) inducing smooth muscle (SM) and mucosal atrophy, increasing collagen synthesis and deposition, decreasing contractile function, mucosal and SM blood flow; oestrogen reverses these effects and increases bladder mass and SM density, primarily by stimulating angiogenesis and increasing blood flow. Twenty adult female New Zealand White rabbits were divided into five equal groups; group 1 served as the control group, and groups 2-5 had a bilateral Ovx. Group 2 received no oestradiol and was assessed 2 weeks after Ovx; groups 3-5 received 17-beta oestradiol from a subcutaneous slow-release tablet 2 weeks after Ovx, which remained in place for a subsequent 2-week period. Group 3 was then assessed after the 2 weeks on oestradiol. Groups 4 and 5 then had their oestradiol tablets removed for 2 weeks and group 4 was assessed after this period off oestradiol. Group 5 then received a new oestradiol tablet that was left in place for an additional 2 weeks. RESULTS: Both groups receiving oestrogen (3 and 5) had a statistically significantly greater bladder weight than both the control group and group 2. The volume fraction of SM paralleled the bladder weight, showing that oestrogen increased the volume fraction of SM whereas Ovx and low oestrogen decreased the SM fraction. The cross-sections of the urethra from groups 3 and 5 were significantly wider than those of either the control or group 1, also being consistent with the structural effects of oestrogen. Intra-arterial phenylephrine increased urethral pressure to a similar level in all groups. The urethral pressure response to intra-arterial acetylcholine shifted from contraction in the control to relaxation in the oestrogen-treated groups. Ovx resulted in a lower vascular density, whereas oestrogen resulted in a significant increase in vascular density (angiogenesis). CONCLUSIONS: Cyclical oestrogen had pronounced structural and pharmacological effects. Low oestrogen decreased the volume fraction of SM, increased collagen, and decreased vasculature, whereas oestrogen mediated a marked hypertrophy of the SM components, decreased the collagen component, and stimulated angiogenesis. Cyclical oestrogen also had marked effects on the responses to intra-arterial acetylcholine, shifting the response from contraction to relaxation.

Animals↗

Role of nitric oxide in urinary bladder function: effect of L-arginine.

BACKGROUND: Evidence indicates that decreased blood flow to the bladder plays a major role in obstructive bladder dysfunction in the rabbit model of partial bladder outlet obstruction (PBOO), and that nitric oxide (NO) regulation of blood flow may be important in modulating the degree of obstructive bladder dysfunction. The specific aim of our study is to determine the effect of feeding rabbits a diet high in L-arginine on the response to PBOO. MATERIALS AND METHODS: Sixteen male NZ White rabbits were separated into 4 groups of 4 each. The rabbits in groups 1 and 3 underwent PBOO. The rabbits in groups 2 and 4 were sham-operated. For 1 week prior to surgery, and 2 weeks postoperatively, each rabbit in groups 1 and 2 was put on a diet containing 7% arginine. Rabbits in groups 3 and 4 were on a normal diet (0.76% arginine). RESULTS: PBOO resulted in a greater increase in bladder weight in the control group than the arginine group. PBOO resulted in a greater decrease in compliance in the control group than the arginine group. The contractile responses to all agents in the arginine control group were greater than in the control normal diet group. PBOO resulted in a greater decrease in the response to field stimulation in the control group than in the arginine group. CONCLUSIONS: These studies clearly demonstrate that feeding rabbits a diet high in L-arginine was beneficial for the control rabbits, and reduced the level of dysfunctions following PBOO.

Animals↗

Comparative effects of in vitro ischemia on contractile responses of mouse and rat bladders to various forms of stimulation.

OBJECTIVES: To compare in an in vitro study the sensitivity of rat and mouse bladders to ischemia and reperfusion. Urinary bladder dysfunction is related to ischemia and reperfusion. Several studies have been conducted in which one animal model was used in the urinary bladder dysfunction experiments, but very few studies have compared the consequences of urinary bladder dysfunction in different species. METHODS: Male rats and mice were anesthetized and their bladders removed. Bladder strips were placed in 15-mL baths containing oxygenated Tyrode's solution with glucose. Strips were stimulated by field stimulation, carbachol, and KCl, and the responses were recorded. Individual strips were switched for 1 hour to Tyrode's with no glucose equilibrated with nitrogen. During this hour, one half of the strips received repetitive stimulation. After the 1 hour of ischemia, the strips were returned to Tyrode's solution with glucose and oxygen for 1 hour without repetitive stimulation. The strips were restimulated as described above. RESULTS: The rat bladder generated significantly greater tension than the mouse bladder. The responses of the mouse, but not the rat, bladder strips were suppressed after repetitive field stimulation in normal solution. In both species, the responses were suppressed under ischemic conditions with or without repetitive stimulation. The responses of the mouse bladders were more sensitive to ischemia and repetitive stimulation than rat bladders. CONCLUSIONS: These results have demonstrated that the mouse bladder is more sensitive to ischemic stress than the rat bladder. This information would be important when choosing species for the study of ischemia and reperfusion.

Animals↗

The effect of tamsulosin on the response of the rabbit bladder to partial outlet obstruction.

AIM: To determine if tamsulosin treatment prevents or decreases the incidence and severity of outlet obstruction-induced bladder dysfunction in rabbits. MATERIALS AND METHODS: Male New Zealand White rabbits were treated with tamsulosin or vehicle for 4 weeks with treatments initiated 1 week prior to sham or obstruction surgery. Cystometry was done on anesthetized rabbits 21 days after surgery. The bladders were then removed, weighed, and prepared for in vitro whole bladder studies. Responses to 32 Hz field stimulation (FS), carbachol, phenylephrine, and KCl were measured. RESULTS: Obstruction resulted in a significant increase in bladder weight, which was unchanged by tamsulosin treatment and a significant increase in micturition pressure in the vehicle-treated group but not in the tamsulosin-treated group. Compliance was significantly decreased in both obstructed groups. The vehicle-treated obstructed rabbits had a very sharp increase in intravesical pressure as the bladder reached capacity; this was not seen in the tamsulosin-treated obstructed rabbits. Tamsulosin did not change the pattern of modifications in contractile responses induced by bladder outlet obstruction. CONCLUSIONS: In vitro responses of vehicle and tamsulosin-treated obstructed rabbit groups in this study were similar. A greater micturition pressure was found for the vehicle-treated obstructed group than for the tamsulosin-treated obstructed group, which was probably due to decreased urethral resistance in the latter. On a functional basis, the higher compliance at capacity and decreased micturition pressure in the tamsulosin-treated obstructed group would be considered beneficial for bladder function.

Adrenergic alpha-Antagonists↗

Estrogen induced functional hypertrophy and increased force generation of the female rabbit bladder.

AIMS: Estrogen is essential for physiological maintenance of the female urogenital tract. It is believed that alterations in female sex hormones play a major role in the etiology and response to urinary tract dysfunctions. In animal studies, ovariectomy (Ovx) results in smooth muscle (SM) weakness and atrophy whereas estrogen supplementation reverses these effects. Our study seeks to establish the mechanisms by which estrogen augmentation results in increased contractility. METHODS: Twenty New Zealand White female rabbits were separated into five groups of four each. Group 1 served as control, rabbits of groups 2-5 were ovariectomized, group 2 ovariectomized received no estradiol, groups 3-5 were given 17-beta estradiol (1 mg/kg/day) by subcutaneous slow release tablet implant for 1, 3, and 7 days, respectively, beginning 2 weeks after Ovx. At the end of the experimental period, each rabbit was anesthetized and the urinary bladder was removed for contractile, histological, and biochemical studies. RESULTS: Ovx resulted in significantly decreased bladder contractile function, whereas bladders tested after estradiol administration showed increased contractility. Ovx resulted in a decrease in SM/collagen ratio, whereas estrogen resulted in an increase. The estrogen receptor (ER) density significantly increased following Ovx. After 1 day of estrogen treatment, the ER density decreased significantly below control levels, but rose progressively during the estrogen treatment. CONCLUSION: The present study demonstrates that estrogen supplementation mediates a "functional hypertrophy," that is a hypertrophy characterized by increased contractile responses to all forms of stimulation, and an increased ratio of SM/collagen.

Animals↗

Effects of dextromethorphan on in vitro contractile responses of mouse and rat urinary bladders.

PURPOSE: Dextromethorphan (DXM) is a cough-suppressing ingredient in a variety of over-the-counter cough and cold medications. Dextromethorphan elevates the threshold for coughing primarily through a central mechanism. At doses recommended for treating coughs the drug is safe and effective. At much higher doses, DXM produces dissociative effects similar to those of phencyclidine and ketamine. Opioid analgesics structurally related to DXM also inhibit bladder contractions and produce urinary retention through a non-opioid mechanism. This study evaluated the direct effects of DXM on in vitro contractile responses of rat and mouse urinary bladders. METHODS: Male rats and mice were anaesthetized and their bladders removed. Bladder strips were suspended in 15 ml oxygenated Tyrode's solution containing glucose. Bladder strip contractions were evoked by field stimulation (FS), carbachol or elevated KCl concentrations and contractile responses recorded. The strips were then exposed to 3 microM (DXM) for 30 min and re-stimulated. This sequence was repeated at 10, 30, and 100 microM DXM. RESULTS: (a) The rat bladder generated significantly greater tension than the mouse bladder. (b) Dextromethorphan produced a dose-dependent inhibition of the response to FS that was approximately equal for rat and mouse bladders. FS at 8 or 32 Hz was significantly more sensitive to DXM inhibition than 2 Hz. (c) The response to carbachol was more sensitive to inhibition by DXM than the responses to FS or KCl. CONCLUSIONS: These results demonstrate that DXM inhibits bladder contractions in vitro and that mouse and rat bladders are affected to approximately the same extent.

Animals↗

Functional changes in bladder tissue from type III collagen-deficient mice.

OBJECTIVE: Collagen fibers impart tensile strength and transfer tension from bladder smooth muscle cells. We have previously shown that fibrotic bladders are characterized by an increased type III:type I collagen ratio. To determine the effect of decreased type III collagen on bladder function, type III collagen-deficient mice (COL3A1) were studied physiologically. METHODS: Bladders from wild-type (+/+) and heterozygous (+/-) COL3A1 mice were biochemically characterized to determine total collagen (hydroxyproline analysis) and collagen subtype concentration (cyanogen bromide digestion and ELISA). Alterations in collagen fiber diameter were assessed by electron microscopy. Bladder muscle strips were used to assess physiologic function. RESULTS: Hydroxyproline content decreased in heterozygous bladders, which had 50% less type III collagen. Wild-type bladders had a biphasic distribution of collagen fiber sizes, whereas heterozygous bladder collagen fibers spanned a broad range. Physiologically, there were no differences in contractile responses between wild-type and heterozygotes when stimulated with ATP, carbachol or KCl, indicating normal contraction via purinergic and muscarinic receptors, and in response to direct membrane depolarization. In contrast, tension generation in heterozygotes was decreased after field stimulation (FS), indicating decreased synaptic transmission. Length-tension studies showed that the heterozygote muscle strips generated less tension per unit length, indicating that they were more compliant than wild-type controls. CONCLUSIONS: Critical levels of type III collagen appear to be a requirement for normal bladder tension development and contraction. Our data show that a decrease in the type III:type I collagen ratio, and altered fiber size, results in a more compliant bladder with altered neurotransmitter function.

Adenosine Triphosphate↗

Effect of maturation and aging on response of rabbit bladder to bilateral in vivo ischemia/reperfusion.

OBJECTIVES: To evaluate the impact of maturation and aging on the effect of bilateral in vivo ischemia/reperfusion on bladder function. METHODS: Male rabbits were separated into three groups by age: immature, mature, and aged rabbits; and each group was subdivided into five subgroups. Each rabbit was subjected to 2 hours of bilateral ischemia. After ischemia, the rabbits in subgroup 1 were killed immediately; the other subgroups were allowed to recover for 1, 7, or 14 days. Separate control (sham-operated) subgroups were not subjected to ischemia. At the end of the experimental period, the bladder was excised, body and base separated, and two strips were prepared from each and mounted in individual baths. The contractile responses to field stimulation and carbachol, adenosine triphosphate, and potassium chloride were determined for the body. The responses to field stimulation alone were determined for the base. RESULTS: The rabbit body and bladder weights of the mature and aged rabbits were significantly greater than that of the young rabbits, but not different from each other. The mature rabbits were significantly more sensitive to ischemia/reperfusion than were the young rabbits. Finally, the aged rabbits were slightly more sensitive to ischemia/reperfusion than the mature rabbits. CONCLUSIONS: The results of our study have shown that the sensitivity of the bladder to ischemia/reperfusion injury increases with age. A very significant increase was found in the sensitivity between young and mature rabbits, with a significantly smaller increase in sensitivity between mature and old rabbits.

Age Factors↗

Alteration of contractile and regulatory proteins in estrogen-induced hypertrophy of female rabbit bladder.

OBJECTIVES: Estrogen is essential to mediate physiologic functions in female bladders. Deficiency of estrogen has been speculated to be an etiologic factor for bladder dysfunction in postmenopausal women. Our previous studies have demonstrated that estrogen supplementation in female rabbits induces a "functional hypertrophy" of the urinary bladder smooth muscle. The present study investigated the alterations in the contractile and regulatory proteins in this model. METHODS: Twenty New Zealand white female rabbits were separated into five groups of 4 rabbits each. Group 1 served as the control, groups 2 to 6 underwent ovariectomy (Ovx), and group 2 served as the Ovx without estradiol treatment group. Two weeks after Ovx, groups 3 to 5 were given 17-beta estradiol (1 mg/kg/day) by subcutaneous implant for 1, 3, and 7 days, respectively. The expression of the contractile and regulatory proteins, such as myosin light chain kinase, rho-kinase, and caldesmon, was analyzed by Western blotting. RESULTS: The expression of myosin light chain kinase was enhanced by estradiol supplementation. The expression of rho-kinase-alpha was increased significantly (20-fold) after Ovx, which was downregulated after estrogen supplementation. No significant change was seen in rho-kinase-beta after Ovx or estradiol supplementation. The expression of caldesmon isoforms was enhanced by 1-day estradiol supplementation but decreased to lower levels than those of the control group by 3 and 7 days of estrogen treatment. CONCLUSIONS: The results of the present study have provided more understanding about the role of the contractile and regulatory proteins in detrusor muscle, in both dysfunctional atrophy induced by Ovx and functional hypertrophy induced by estrogen supplementation.

Animals↗

The immediate effect of castration on female rabbit bladder blood flow and tissue oxygenation.

BACKGROUND: The female urinary bladder is a target organ for estrogen. Reductions in circulating estrogen have been associated with urothelial and vaginal atrophy and bladder disorders including incontinence and increased incidence of bladder infections. We determined the effect of short-term ovariectomy on sex hormones, bladder blood flow, and tissue oxygenation in the rabbit model. MATERIALS AND METHODS: Female New Zealand White rabbits were ovariectomized and evaluated on 1, 3, and 7 days after ovariectomy. Tissue oxygenation (pO2) and blood flow were measured with oxylab system of real time measurements. Serum estrogen and progesterone were determined at sacrifice. Tissue hypoxia was localized histologically using Hypoxyprobe-1 immunohistochemistry. RESULTS: Short-term ovariectomy caused rapid decreases in serum estrogen and progesterone, significant decreases in urothelial oxygenation and blood flow. No significant decreases in blood flow or oxygenation were noted for the detrusor smooth muscle. Immunohistochemistry confirmed the presence of urothelial hypoxia at all times after ovariectomy. Bladder muscle did not demonstrate significant levels of hypoxia. CONCLUSION: The bladder urothelium is extremely sensitive to short-term ovariectomy, with significant urothelial hypoxia seen by post-ovariectomy day 1. Urothelial hypoxia may play a significant role in pelvic pain syndromes, incontinence, and increased susceptibility to bladder infection.

Animals↗

Estrogen induces angiogenesis of the female rabbit bladder.

Postmenopausal bladder dysfunction has been speculated to involve decreased circulating estrogen levels. It is our hypothesis that estrogen induces bladder dysfunctions by modulating blood flow to the bladder, i.e. low estrogen reduces blood flow to the bladder, whereas high estrogen increases blood flow. Our previous studies have demonstrated that estrogen administration in female rabbits induces a 'functional hypertrophy' of the urinary bladder smooth muscle represented by increased smooth muscle mass, which corresponds to increased contractile responses to all forms of stimulation. The present study investigates the effect of estrogen on vasculature density and distribution. Twenty-four female New Zealand white rabbits were separated into six groups of four rabbits each. Group 1 served as controls. Groups 2-6 were ovariectomized. Two weeks after ovariectomy (Ovx), groups 3-6 were given 17-beta estradiol (1 mg/kg per day) by s.c. implant for 1, 3, 7, and 14 days respectively. Blood vessel density and distribution were evaluated by immunohistochemistry and quantitative image analyses. Ovx resulted in significant vascular degeneration and decreased density, whereas estradiol administration mediated a significant angiogenic effect characterized by increased vascular density, and distribution of new vasculature within the smooth muscle bundles of the detrusor. Estradiol-induced vasculogenesis corresponds with our previously demonstrated increase in blood flow to the bladder and increased contractility. The most interesting aspect of these studies is the increased vascularization localized within the muscle bundles rather than between the muscle bundles, which may be important in the link between estrogen and increased incidence of cancers.

Animals↗

Effect of partial outlet obstruction on nitrotyrosine content and distribution within the rabbit bladder.

PURPOSE: Evidence indicates that free radicals are etiological factors in obstructive bladder disease. However, it is not clear which species of reactive oxygen or nitrogen species mediate the damage. The current studies were designed to determine if partial outlet obstruction in rabbits results in the generation of nitrotyrosine (NT). MATERIALS AND METHODS: Sixteen rabbits were separated into four groups of four. The rabbits in groups 1 and 2 underwent sham operation while rabbits in groups 3 and 4 underwent partial outlet obstruction. The rabbits in groups 1 and 3 were evaluated after 1 week of obstruction and the rabbits in groups 2 and 4 were evaluated after 2 weeks of obstruction. A separate group of four controls were evaluated simultaneously with the sham and obstructed rabbits. Four rabbits from each group were evaluated after 1 and 2 weeks of obstruction. Four control rabbits were also evaluated. Isolated strips were evaluated for contractile responses and NT content of the mucosa and muscle were quantitated by Western blot analysis. RESULTS: (1) The mucosa contains both 42 and 62 kD proteins exhibiting a strong nitrotyrosine signal; the muscle presents a signal only at 62 kD. (2) The sham operations had no effect on nitrotyrosine distribution or content. (3) The nitrotyrosine of both mucosal proteins and the muscle protein are increased in the 1 week obstructed bladder; whereas, only the 62 kD signal is increased in the two week obstructed bladder mucosa. (4) The contractile response to FS are reduced to a significantly greater degree than the responses to carbachol, KCl, or ATP. CONCLUSIONS: These studies clearly demonstrated that partial outlet obstruction in rabbits results in significant increases in nitrotyrosine within the bladder and may contribute to the contractile dysfunctions mediated by partial outlet obstruction.

Animals↗

Effect of ethanol on the response of the rat urinary bladder to in vitro ischemia: protective effect of alpha-lipoic acid.

PURPOSE: Ethanol exposure has been used to demonstrate the increase of oxidative stress to a variety of tissues. We studied the effect of ethanol on the response of isolated strips of rat bladder to in vitro hypoxia in the absence of glucose (in vitro ischemia). Secondly, we determined if alpha-lipoic acid (LA) could alter the response to ethanol + in vitro ischemia. METHODS: Sixty-four rats were used for the these experiments. Each rat was anesthetized and its urinary bladder excised. The bladder body was cut into two longitudinal strips and each strip mounted in individual baths filled with oxygenated Tyrodes solution containing glucose at 37 degrees C. Ethanol (0.3%, 1%, or 3%) was placed in the first six baths (two strips at each concentration). The last two baths did not receive ethanol. Each strip was incubated for 1 h and then stimulated with field stimulation at 2, 8, and 32 Hz. Each strip was stimulated with 10 microM carbachol, washed three times with fresh oxygenated buffer and ethanol re-added to their respective baths. Each strip was then stimulated with 120 mM KCl and washed three times as before. Strips were then subjected to 1 h in vitro ischemia (incubation in the absence of glucose with Tyrode's equilibrated with nitrogen instead of oxygen). During the ischemic period, each strip was stimulated for 5 s every 10 min by 32 Hz FS to simulate hyperreflexia. At the end of the hour, the tissues were incubated for an additional hour in the presence of oxygen + glucose and subjected to a second series of stimulations as before. At all times, ethanol was maintained in baths 1-6. In set 2, 1% ethanol was added to the first six baths. LA was added to every other bath, and the experiments performed as mentioned earlier. RESULTS: (a) Ethanol at 0.3% or 1% had no effect on the contractile responses prior to exposure to in vitro ischemia; 3% was inhibitory. (b) In vitro ischemia mediated a significant decrease in the contractile responses to all forms of stimulation except for carbachol. (c) Ethanol mediated a dose-response enhancement of the contractile dysfunctions caused by in vitro ischemia. (d) LA completely reversed the effects of ethanol on contractile responses following in vitro ischemia except for carbachol. CONCLUSIONS: The results demonstrate that direct exposure to ethanol significantly enhanced contractile dysfunctions mediated by in vitro ischemia followed by re-oxygenation and that the presence of LA significantly inhibits this effect of ethanol.

Animals↗

Effect of ethanol on protection of urinary bladder function by grape suspensions.

OBJECTIVES: To compare the protective effects of grape suspensions prepared in an aqueous vehicle with grape suspensions prepared in an 8% ethanol vehicle in rabbits subjected to partial outlet obstruction. The hypothesis was that the presence of ethanol would increase the absorption of the beneficial components of the grape suspensions and thus increase their protective ability. The use of ethanol in these studies was not to simulate wine. METHODS: A total of 48 New Zealand white rabbits were separated into eight groups of 6 rabbits each. Groups 1 and 3 were pretreated by oral gavage for 3 weeks with grape suspensions in water; groups 2 and 4 were treated with vehicle. Groups 5 and 7 were treated with the grape suspensions in 8% ethanol, and groups 6 and 8 were treated with ethanol vehicle. Groups 1, 2, 5, and 6 underwent sham operations, and groups 3, 4, 7, and 8 underwent partial outlet obstruction. Three weeks after surgery, the rabbits were evaluated. RESULTS: The bladder weight had significantly increased in all obstructed groups. The contractile responses to field stimulation and carbachol were reduced in all obstructed groups, although the responses in both grape-treated groups were greater than both vehicle-treated groups. The contractile responses to potassium chloride were significantly reduced by partial outlet obstruction in both obstructed groups similarly. CONCLUSIONS: Both grape suspensions provided protection against obstructive-induced bladder dysfunction. The ethanol preparation of the grape suspension was not better than the aqueous preparation.

Animals↗

Effect of strip length on the contractile dysfunction of bladder smooth muscle after partial outlet obstruction.

OBJECTIVES: Partial outlet obstruction mediates decreased contractile responses and increased collagen synthesis; however, it is not known to what extent the increased collagen contributes to contractile dysfunction. METHODS: Sixteen WNZ rabbits were divided into three groups: control, 2-week obstructed, and 2-week sham. Each rabbit was anesthetized, and the bladder was excised and cut into equal width strips of 0.5, 1.0, and 2.0-cm lengths. The contractile responses to field stimulation, carbachol, potassium chloride, and adenosine triphosphate were determined. At the end of the experiment, each strip was fixed in formalin and immunostained for collagen. RESULTS: The contractile responses for the control and sham strips were similar for all strip lengths. In obstructed tissue, the shorter strip lengths generated significantly more tension per cross-sectional area than did the longer strips. The collagen density and distribution were similar for the control and sham bladders. The obstructed bladders had significantly increased collagen deposits between and within the smooth muscle bundles and cells. CONCLUSIONS: Because the relationship between strip size and contraction were similar for field stimulation, carbachol, and potassium chloride, it is the increased density of connective tissue within and between the muscle bundles and fibers that interferes with contraction (ie, the greater the strip length, the greater the interference and the greater the contractile dysfunction). Therefore, both functional and structural alterations in the obstructed bladder participate in contractile dysfunction.

Animals↗

Effect of age on rabbit bladder function and structure following partial outlet obstruction.

PURPOSE: We determined whether young and old rabbits respond differently to partial bladder outlet obstruction. MATERIALS AND METHODS: A total of 16 male New Zealand White rabbits were separated into 2 groups of 8 each. Group 1 consisted of young rabbits (age 7 weeks) and group 2 consisted of old rabbits (age 2 years). Four rabbits per group underwent partial outlet obstructions and 4 underwent sham operation. Four weeks following surgery individual bladder strips were used for contractile studies and the remaining tissue was examined histologically. RESULTS: Contractile responses to all forms of stimulation between the young and old sham operated groups were similar. Contractile responses to all forms of stimulation were significantly decreased to the same degree in the 2 obstructed groups. However, the rate of tension generation to field stimulation was decreased to a significantly greater degree in young vs old bladders. Although young and old bladders showed smooth muscle hypertrophy, older rabbits showed significantly greater thickening of the serosa than young rabbits. Young rabbits showed significant inflammation, hemorrhage and expansion of the lamina propria, whereas old rabbits showed none of these characteristics. CONCLUSIONS: Although there were only minor differences in the physiological response of young and old bladders to obstruction, young rabbits showed a significantly greater degree of histological damage. This may have been due to the thinner wall and greater sensitivity to distention.

Aging↗

Protective effects of grape suspension on in vivo ischaemia/reperfusion of the rabbit bladder.

OBJECTIVE: To investigate the potential protective effect of a grape suspension in a rabbit model of in vivo bilateral ischaemia/reperfusion (I/R), which is a causal factor in obstructive bladder dysfunction. MATERIALS AND METHODS: Six groups of four New Zealand White rabbits were treated by twice-daily gavage with aqueous grape suspension (groups 1-3) or sugar-water vehicle (groups 4-6) for 3 weeks. Groups 1 and 4 then received bilateral ischaemia for 2 h, and groups 2 and 5 received bilateral ischaemia for 2 h and reperfusion (recovery) for 1 week. Groups 3 and 6 were controls (sham-operated). The effects on cystometry, in vitro contractile responses, and morphology were evaluated. RESULTS: Ischaemia resulted in significant reductions in the contractile responses to all forms of stimulation in vehicle-fed rabbits, whereas there were no reductions in grape-fed rabbits. Contractile responses were significantly reduced in both I/R groups, but significantly more in vehicle-fed than in grape-fed rabbits. Immunohistochemical studies showed less hypoxia in the bladders of grape-fed rabbits than in vehicle-fed rabbits for both ischaemia-only and I/R groups. CONCLUSIONS: Feeding rabbits with grape suspension provided significant protection against the hypoxic effects of bilateral ischaemia and I/R.

Animals↗