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Biomedical subjects

P Horan

Publications and source records attributed to P Horan.

At least 19 recordsLinked to original sources
PubMed2001

Vascular response of the rabbit bladder to chronic partial outlet obstruction.

Partial outlet obstruction of the rabbit urinary bladder results, initially, in a rapid increase in bladder mass and remodeling of the bladder wall. Previously, it was shown that this response was characterized by serosal growth (thickening) which was apparent after 1 day of obstruction, before any visible vascularization was observed. After 1 week of obstruction, significant microvessel formation was seen in the transition region between the detrusor smooth muscle and the thickening serosa; after 2 weeks the entire serosa was vascularized. In this study we investigated the effect of chronic (4 week) partial outlet obstruction on microvessel density and distribution in the bladder wall immunohistochemically using CD31 as a marker for vascular endothelium. Transverse sections of bladder wall were examined after 4 weeks of no surgery, sham surgery or partial obstruction. The microvessel density of the obstructed rabbit bladder mucosa and detrusor smooth muscle increased relative to augmentation of these compartments while new vessels appeared in the thickening serosa. Although vessel density did not change with obstruction a significant shift in mean vessel circumference to the left occurred indicating a significant increase in the number of microvessels and small vessels consistent with angiogenesis.

Adenosine Triphosphate↗
PubMed2001

The response of fetal sheep bladder tissue to partial outlet obstruction.

PURPOSE: We characterized the response of fetal ovine bladder strips to stimulated contraction and relaxation, and compared this response to that of strips from the pregnant mother and those obtained after a short duration of fetal bladder outlet obstruction. MATERIALS AND METHODS: Sham surgery or bladder obstruction was performed in fetal sheep at 90 days of gestation (term 147 days). Bladder tissue was obtained 3 and 5 days later. Isolated strips of full-thickness bladders from fetuses and pregnant females were mounted individually in Tyrode's solution containing glucose. The strips were subjected to electrical field stimulation. Alternate strips were stimulated by adding carbachol, adenosine triphosphate and KCl. Each strip stimulated by carbachol also underwent field stimulation in the presence of carbachol. Relaxation was also tested using isoproterenol and nitroprusside. RESULTS: The response of isolated strips to field stimulation showed phasic contraction or biphasic response, consisting of initial phasic contraction followed by phasic relaxation and a return to control tension after the end of stimulation. In fetal bladder strips field stimulation at all frequencies after carbachol stimulation produced phasic relaxation or a biphasic response with an initial relaxation phase followed by phasic contraction. This field stimulated relaxant response was not present in adult female bladder strips. In addition, field stimulation stimulated relaxation was completely eliminated by pretreatment with N-nitro-L-arginine-methyl ester, indicating that relaxation was nitric oxide mediated. The fetal responses to all forms of stimulation and relaxation were significantly greater than those of pregnant females. After 5 days or greater of obstruction the responses to field stimulation were reduced significantly. In contrast, there were no significant differences in contractile responses to adenosine triphosphate, carbachol or KCl, or the relaxant response to field stimulation after obstruction. However, there was a significant reduction in relaxant responses to isoproterenol and nitroprusside. CONCLUSIONS: In mid gestation sheep fetus contractile responses to field stimulation, adenosine triphosphate, carbachol and isoproterenol are well developed. The fetal ovine bladder shows a strong neuronal nitric oxide response that is not present in the pregnant mother and is maintained after short-term obstruction.

Animals↗
PubMed2000

Vascular response of the rabbit bladder to short term partial outlet obstruction.

Partial bladder outlet obstruction of the rabbit bladder results in a rapid increase in mass characterized by remodeling of the bladder wall. In this study we investigated the effect of partial outlet obstruction on microvessel density and distribution in the bladder wall immunohistochemically using CD31 as a marker for vascular endothelium, and on blood flow using a fluorescent microsphere technique. Transverse sections of bladder wall were examined after 0 (unobstructed), 1, 3, 5, 7, and 14 days of obstruction. The microvasculature of obstructed rabbit bladder mucosa and detrusor smooth muscle apparently increased relative to augmentation of these compartments, while new vessels appeared in the thickening serosa. These vascular changes correlated with results showing that, at 1 week after obstruction, blood flow (ml/min/g tissue) to the mucosa and detrusor was unchanged. Thickening of the serosa, apparent after 1 day of obstruction, began before its vascularization. Then, 1 week post-obstruction, there was significant microvessel formation in the transition region between the detrusor smooth muscle and the increasing serosa; after 2 weeks, the entire serosa was vascularized. The vascularization of the muscle-serosal transition region and then the remaining serosa apparently precedes fibroblast differentiation, providing blood supply and thus metabolic support for this process. All obstructed rabbit bladders in this study were in a state of compensated function based on their weights. Our working hypothesis is that blood flow per unit tissue mass is normal in compensated obstructed bladders, thus allowing for normal contractile function and cellular metabolism. The results of this study indicate the presence of an augmented microvasculature in compensated obstructed rabbit bladders that provides adequate blood perfusion for normal function.

Animals↗
PubMed2000

Comparative physiology and biochemistry of rat and rabbit urinary bladder.

OBJECTIVE: To compare directly the biochemistry and contractile responses of rat and rabbit bladder to different stimuli. Materials and methods Sexually mature male New Zealand White rabbits and Sprague Dawley rats were compared. Each bladder was excised while the animal was anaesthetized; longitudinal bladder strips were cut and then mounted in an organ bath. Tension (2 g) was placed on all strips and each underwent field stimulation (FS) for a total of 20 s at 1-32 Hz, 1 ms and 80 V and was exposed to carbachol (100 micromol/L), ATP (2 mmol/L) and KCl (120 mmol/L). The tension was monitored continually using a polygraph and data stored digitally in a computer. The responses to each stimulus were determined as the maximum tension generated, maximum rate of tension generation and duration to a maximum response. The Ca2+- ATPase activity of the rat and rabbit bladder was determined. Bladder pressures were then predicted from the strip data using Laplace's law and compared with published values. RESULTS: Contractile responses (per unit tissue mass) of rat bladder strips were significantly greater than those of rabbit bladder strips at all frequencies of FS and to carbachol, KCl and ATP. The rate of contractile force generated by rat bladder strips in response to all stimuli were significantly greater than that generated by rabbit strips. Rabbit bladder strips took significantly longer to generate maximum tension than did rat bladder strips in response to pharmacological stimuli. In response to FS, rat strips took significantly longer than rabbit strips to generate maximum tension. Although the predicted rat bladder pressures were significantly greater than those for rabbit, the predicted pressures for both the rat and rabbit were significantly lower than the pressure responses of the isolated whole bladder model. The contractile data correlated well with the Ca2+-ATPase activity data; rat bladder had seven times the enzyme activity of rabbit bladder. CONCLUSION: Per unit mass, rat bladder is capable of generating more than five times the tension of rabbit bladder. Similarly, the rate of tension generation by rat bladder is three to five times greater than that by rabbit bladder. The duration to maximum tension generated in response to FS compared with pharmacological stimuli was affected by the inherent difference in the rate of contractile response to electrical activation compared with agents which diffuse through tissue, and by the difference in size between rat and rabbit bladder smooth muscle cells.

Adenosine Triphosphate↗
PubMed2000

Intermittent catheterization limits rabbit bladder dysfunction in response to partial outlet obstruction.

INTRODUCTION: The initial response of the urinary bladder to outflow partial obstruction consists of distension, followed by a rapid increase in mass and concomitant functional adaptations. Subsequently, an indeterminate period of stabilized function and little increase in mass occurs (compensation). Finally, bladder mass again progressively increases, accompanied by deleterious changes in bladder morphology, biochemistry and pharmacology, and progressive loss of function (decompensation). The reported study was designed to determine whether limiting the level of bladder distension, using intermittent catheterization (IntCath), could protect the bladder from decompensation. MATERIALS AND METHODS: Sixteen male New Zealand White rabbits were separated into 4 groups of 4 rabbits each: control, control with IntCath, obstructed, and obstructed with IntCath. IntCath was performed with the animals under inhalation anesthesia. An 8 Fr. catheter was inserted through the urethra into the bladder every 8 hours and the urine drained. After 14 days of obstruction, bladders were removed from all rabbits; longitudinal strips were cut from the bladder body and suspended in individual organ baths. Contractile responses to field stimulation (FS), KCl, ATP, and carbachol were measured. RESULTS: There were no significant differences between control rabbits and controls with IntCath in bladder weights, compliance, and contractile responses to all stimuli. Bladder weights of both obstructed groups increased significantly compared to those of both control groups. Bladder weights of obstructed rabbits increased to a significantly greater extent than did those of obstructed rabbits with IntCath. Bladder compliance in the obstructed group was significantly lower than compliance in both control groups and in obstructed rabbits with IntCath. Both obstructed groups exhibited significantly decreased contractile responses to FS, ATP and KCl, compared to control groups. The response of the obstructed group with IntCath to FS and carbachol was significantly greater than the responses of the obstructed group without IntCath. CONCLUSIONS: These findings show that limiting distension with IntCath reduces the magnitudes of the increased bladder mass, the loss of bladder wall elasticity (compliance), and the impaired contractile responses which occur secondary to outflow obstruction.

Animals↗
PubMed2000

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 innervation of detrusor smooth muscle (SM). The effect of partial outlet obstruction on the physiological responses to field stimulation (FS) (nerve mediated contraction) and carbachol (receptor mediated contraction) were correlated with the structure and innervation of the detrusor smooth muscle (SM) of the same animal during a 70 day period. MATERIALS AND METHODS: 28 rabbits were subjected to 1 to 70 days of mild partial outlet obstruction. Sham operated rabbits were euthanized at 7, 14, 28, and 70 days post-obstruction. At each time period, isolated strips of bladder body were mounted in individual baths and the contractile response to FS and carbachol determined. Three additional strips from each bladder were fixed for electron microscopy. RESULTS: Bladder mass increased rapidly during the first 7 days after obstruction, was constant for the next 7 days, and then continued to increase gradually. Dysfunction of the contractile response to FS was noted as early as 3 days and progressively increased over the 70-day study period. The decrease in the response to FS increased at a significantly faster rate than the decrease in the contractile response to carbachol. In ultrastructure studies, at 3 and 7 days post-obstruction the majority of SM cells displayed the characteristics of hypertrophy. At 28 days some SM cells displayed loosely packed myofilaments and an irregular distribution of sarcoplasmic dense bodies. At 70 days swollen mitochondria were present in all cell types of the bladder wall. Evidence of axonal degeneration was first observed at 7 days post-obstruction and became more extensive thereafter. No evidence of mitotic figures, nerve growth cones or regenerating SM cells was observed. CONCLUSIONS: Prolonged partial bladder outflow obstruction is accompanied by a progressive decrease in contractility of SM. The present study describes the structural damage that occurs in the bladder wall in response to partial outlet obstruction and correlates these observations with the contractile dysfunction with which it is associated. Furthermore, mitochondrial damage in vessels and fibroblasts is suggestive of bladder wall ischemia.

Animals↗
PubMed2000

Improved contractility of obstructed bladders after Tadenan treatment is associated with reversal of altered myosin isoform expression.

PURPOSE: Tadenan is a plant extract from Pygeum africanum used in the treatment of benign prostatic hyperplasia, to protect the bladder from contractile dysfunction induced by partial bladder outlet obstruction (BOO). The aim of the present study was to determine whether the Tadenan-induced return of detrusor contractility affects the expression of myosin isoforms, which differ at the C-terminal (SM1 and SM2) and the N-terminal regions (SM-A and SM-B). MATERIALS AND METHODS: Four groups of New Zealand White rabbits (3 to 5 kg., 4 to 6 rabbits per group) were either partially obstructed by ligation of the urethra (groups 1 and 2) or not obstructed (groups 3 and 4). After 2 weeks, rabbits from groups 2 and 4 received Tadenan in peanut oil (vehicle) orally at 100 mg. /kg./day for 3 weeks and rabbits in groups 1 and 3 received vehicle only. Rabbits were sacrificed and bladders were removed and weighed. Contractility studies were performed on isolated strips of detrusor and the remaining muscular layer from the bladder body was used to study the expression of myosin heavy chain (MHC) isoforms at mRNA (SM1, SM2, SM-A, and SM-B) and the protein (SM1 and SM2) levels by RT-PCR and SDS-PAGE analyses, respectively. RESULTS: Tadenan significantly reduced the effect of BOO on bladder mass. The diminished contractile response to field stimulation and carbachol secondary to urethral obstruction was significantly reversed by Tadenan treatment. The relative ratios for MHC isoforms were altered at the mRNA (SM2:SM1 and SM-A:SM-B) and protein (SM2:SM1) levels in obstruction. Upon treatment with Tadenan, the ratio of these isoforms returned to normal, as shown at the mRNA levels. In addition, the altered relative ratio of SM2:SM1 at the protein level also returned to nearly normal values after treatment. CONCLUSIONS: Improvement of obstruction-induced contractile dysfunction of the detrusor following treatment with Tadenan is associated with changes in the expression of myosin isoforms. The alteration in the expression of myosin isoforms associated with obstruction-induced hypertrophy is reversed close to normal in the detrusor smooth muscle from Tadenan-treated obstructed rabbits.

Animals↗
PubMed1999

Effect of diltiazem and pinacidil on the response of the rabbit urinary bladder to repetitive stimulation and in vitro ischemia.

The effect of repetitive stimulation, in the presence and absence of diltiazem or pinacidil, on the contractile responses of isolated strips of rabbit bladder detrusor to field stimulation and carbachol, after 2 hr of incubation in a medium that serves as an in vitro model of ischemia (oxygen and substrate depleted Tyrode's solution), was determined. Our results are summarized as follows: a) The magnitude of the contractile dysfunctions after in vitro ischemia was enhanced by repetitive stimulation. b) Pre-incubation of isolated strips of detrusor with diltiazem (50 microM) inhibited the contractile responses to field stimulation (FS) and carbachol by 43 and 50%, respectively. Pinacidil (100 microM) inhibited the contractile responses to FS and carbachol by 37 and 32%, respectively. c) Neither diltiazem nor pinacidil protected the bladder strips against the effects of 2 hr of incubation in in vitro ischemia medium. However, d) both pinacidil and diltiazem reduced the level of contractile dysfunctions induced by repetitive stimulation. In conclusion, the contractile response to FS was significantly more sensitive to in vitro ischemia and repetitive stimulation than was the contractile response to carbachol. Both diltiazem and pinacidil protected the contractile responses to FS and carbachol from the degenerative effects of repetitive stimulation, but not from the effects of in vitro ischemia.

Animals↗
PubMed1999

Sucrose diuresis protects rat bladder from outlet partial obstruction-induced contractile dysfunction.

OBJECTIVES: Evidence is accumulating that bladder dysfunction caused by experimental partial obstruction of the bladder outlet can be reduced or reversed by treatment that results in upregulation of bladder function, even in the presence of obstruction. Inducing diuresis in rats or rabbits results in a significant increase in bladder mass and increased contractility in response to stimulation. The objective of the present study was to determine whether diuresis-induced amplification of bladder function in the rat could protect the bladder from contractile dysfunctions caused by partial outlet obstruction. METHODS: Thirty-two rats were separated into four groups of 8 rats each. Groups 2 and 4 were fed 5% sucrose instead of water; groups 1 and 3 were fed only water. Three weeks later, partial outlet obstructions were created in groups 3 and 4. After 4 weeks of obstruction, all bladders were rapidly excised and cut into longitudinal strips; each strip was mounted in an isolated muscle bath for contractile studies. RESULTS: Sucrose-induced diuresis caused a moderate but significant increase in bladder mass. Partial outlet obstruction stimulated significant increases in bladder mass in both water-drinking and sucrose-drinking groups; the bladder mass of sucrose-drinking rats, however, increased less than that of water-drinking rats. In water-drinking rats, partial outlet obstruction resulted in significantly decreased bladder strip contractility in vitro in response to field stimulation (1 to 32 Hz), carbachol (0.1 to 22 microM), and KCl (120 mM). After 3 weeks of sucrose-induced diuresis, partial obstruction of the rat bladder outlet did not result in decreased in vitro contractile responses to any form of stimulation applied. CONCLUSIONS: Sucrose-induced diuresis caused an increase in bladder mass and an increase in contractile strength, consequently protecting the rat bladder from the contractile dysfunctions that usually follow partial outlet obstruction.

Animals↗
PubMed1999

Metabolic aspects of urinary bladder filling.

Urinary bladder compliance allows the bladder to fill to near capacity without a large increase in intravesical pressure. Bladder compliance is composed of two interrelated factors: passive characteristics of the connective tissue elements of the bladder, and active properties of the smooth muscle elements. The tension generated by the smooth muscle elements can significantly affect bladder compliance. This study utilized an in-vitro whole-bladder model in rabbits to determine the effects of hypoxia, alterations in calcium concentrations, and muscarinic agonists and antagonists on bladder capacity and compliance. The urinary bladder was excised together with a short segment of proximal urethra. A catheter was inserted into the bladder via the dome and the urethra was canulated with a saline-filled tube. The bladder was mounted in an isolated bath containing Tyrode's buffer. The catheter was connected to a pressure transducer to monitor the intravesical pressure and connected to a saline-filled i.v. bag. The weight of the saline bag was continually monitored. The height of the saline bag was set to 80 mmH2O above the baseline intravesical pressure. Bladder filling was started by opening the bladder to the saline reservoir. Intravesical pressure, rate of pressure increase, rate of volume increase, and maximal volume were digitally recorded. The bladder filling was repeated while the whole bladder was subjected to hypoxia, high calcium concentration, the presence of EGTA, carbachol, atropine and tetrodotoxin, respectively. Results are summarized as follows: (a) control bladder filling was biphasic, there was an initial rapid rise in intravesical pressure followed by a slower linear rise to the pre-set pressure; (b) hypoxia significantly decreased the initial rate of the rise in intravesical pressure, increased the rate of bladder filling, and significantly increased final bladder volume; (c) incubation of the bladder in the presence of EGTA also significantly decreased the initial rate of intravesical pressure rise, increased the rate of filling and also significantly increased the final bladder volume; (d) high concentrations of calcium increased the initial rate of rise in intravesical pressure; (e) carbachol significantly increased the rate of intravesical pressure rise, decreased the rate of bladder filling, and significantly decreased final bladder volume; (f) atropine and tetrodotoxin (TTX) had no effects on bladder filling. In summary, alterations in muscle tone had significant effects on bladder capacity and compliance.

Animals↗
PubMed1999

Correlation of EGTA and calcium-blocking agents on the response of the bladder to in vitro ischemia.

The effects of repetitive field stimulation (model of hyperrelexia) on the responses of isolated strips of rabbit urinary bladder to FS and carbachol were evaluated under a variety of incubation conditions. Compared to control conditions, 2 h of repetitive FS in normal, oxygenated Tyrode's solution followed by incubation for 1 h with no stimulation resulted in a 50% decrease in contractile response to FS and a 30% decrease in the response to carbachol. Incubation in the absence of O2 and glucose was used as an in vitro model for ischemia. Repetitive stimulation during in vitro ischemia resulted in a significantly greater decrease in the contractile responses to FS and carbachol than did in vitro ischemia without repetitive stimulation. The magnitude of contractile dysfunctions in response to both stimuli were significantly reduced in the presence of EGTA (calcium chelator), diltiazem (calcium channel blocker) or pincidil (potassium channel opener). Incubation with thapsigargin (SR calcium uptake inhibitor) + ryanodine (SR calcium storage inhibitor) had no effect. The results of these studies indicate that inhibition of Ca2+ entry reduces the contractile dysfunctions induced by repetitive stimulation in the presence of in vitro ischemia. Inhibition of Ca2+i storage and release had no significant effect on the magnitude of contractile dysfunctions induced by repetitive stimulation an in vitro ischemia.

Animals↗
PubMed1999

Rabbit versus rat urinary bladder: effects of in vitro hypoxia.

PURPOSE: Studies indicate that bladder hypoxia may be an etiological factor for lower urinary tract dysfunction. Rat and rabbit are two species of experimental animals used frequently to study lower urinary tract function and dysfunction. The objective of this study was to compare directly effects of in vitro hypoxia on contractile responses of rat and rabbit urinary bladder to different forms of stimulation. METHODS: Sexually mature male New Zealand White rabbits and Sprague-Dawley rats were compared. Each bladder was excised while the animal was anesthetized, and longitudinal bladder strips were cut, then mounted in organ baths. A tension of 2 g was placed on all strips. Effects of 1, 2, 3 and 4 h hypoxia followed by 1 h of reoxygenation on contractile responses of bladder strips to field stimulation (FS), carbachol (100 micromol/l), ATP (1 mmol/l) and KCl (120 mmol/l) were determined. RESULTS: Contractility, per unit tissue mass, of rat bladder strips was significantly greater than that of rabbit bladder strips in response to FS (all frequencies), carbachol, KCl and ATP. Hypoxia (followed by reoxygenation) resulted in time-dependent progressive reduction in contractile responses of bladder strips to all stimuli. Rat bladder was significantly more sensitive to hypoxia than rabbit bladder in response to FS and carbachol. Hypoxia induced similar effects on rat and rabbit bladder responses to ATP and KCl. CONCLUSION: Rat bladder neurogenic and cholinergic responses are significantly more sensitive to hypoxia than are those of rabbit bladder, which may be due to the rat bladder's greater contractile force generation and previously reported higher Ca2+-ATPase activity.

Animals↗
PubMed1999

Effects of in vivo ischemia on contractile responses of rabbit bladder to field stimulation, carbachol, ATP and KCl.

Rabbits were subjected to bilateral ischemia for 3, 6, or 18 h then euthanized and their bladders excised. Isolated strips of rabbit bladder detrusor were incubated in normal Tyrode's solution and contractile responses to FS, carbachol, ATP, and KCl measured. Maximal contraction, maximal rate of tension generation, and length of time to maximal contraction were determined. These studies revealed that contractile responses to FS (neurogenic stimulation) were most affected by ischemia. Contractile responses to carbachol, ATP and KCl were all similarly sensitive to ischemia.

Adenosine Triphosphate↗
PubMed1999

Effects of Unilateral Ischemia on the Contractile Response of the Bladder: Protective Effect of Tadenan (Pygeum africanum Extract).

Recent studies indicate that localized (regional) ischemia may play an important role in the etiology of the contractile dysfunctions secondary to partial outlet obstruction. Pretreatment with Tadenan® (Pygeum africanum extract) has been shown to protect the rabbit bladder against the development of both contractile and biochemical dysfunctions induced by partial outlet obstruction, possibly by protecting the bladder against ischemic injury. The current study was designed to determine if Tadenan pretreatment of rabbits protected the bladder against the development of contractile dysfunctions induced by unilateral ischemia and to correlate effects in the presence and absence of Tadenan with the molecular response in relation to two of the most prominent genes activated by both ischemia and partial outlet obstruction: Hsp-70 and c-myc. Male New Zealand rabbits were separated into four groups of six rabbits each. Three rabbits of each group were treated for 3 weeks with Tadenan. The other three rabbits of each group were untreated controls. Each rabbit in Groups 2, 3, and 4 was anesthetized, and all major arteries entering on the right side of the bladder were li-gated. Rabbits in Group 1 were nonischemic. After 30, 60, and 120 minutes of unilateral ischemia, the rabbits in groups 2, 3, and 4, respectively, were euthanized. The bladders were removed, and contractility studies were performed on strips of detrusor muscle isolated from both the ischemia and nonischemic sides. The balance of the ischemic and nonischemic sides were frozen and stored in liquid nitrogen until analyzed for the expression of Hsp-70 and for c-myc. Tadenan pretreatment protected the nonischemic side of the bladder from the development of contractile dysfunctions, and unilateral ischemia resulted in a 10-fold increase in the expression of both Hsp-70 and c-myc in the bladders isolated from the Tadenan-treated rabbits. These results indicate that Tadenan has a protective effect against ischemic damage to the bladder. This protection may involve enhanced expression of Hsp-70 and other genetic factors.

Journal Article↗
PubMed1998

Use of abdominal fascia to create partial outlet obstruction in rabbits.

Partial outlet obstruction has been used for a considerable period of time as an animal model for the urodynamic changes that occur with the progressive obstruction of benign prostatic hyperplasia (BPH). Although there are many models of partial outlet obstruction, one common feature is that the degree of obstruction produced is inconsistent. The current study evaluates the responses of the bladder to a partial outlet obstruction created using an autologous fascial collar from harvested rectus fascia. The results demonstrate that although there was a moderate and variable increase in bladder mass, the alterations in the contractile responses to field stimulation (FS), carbamyl choline (carbachol), KCl, and adenosine 5'-triphosphate (ATP) were less severe than other models of partial outlet obstruction. Specifically, there was an approximate 40% decrease in the magnitude of the contractile response to FS but no significant changes in the magnitude of the contractile responses to carbachol, KCl, or ATP. Further analysis of the contractile responses demonstrated that there was a greater decrease in the rate of tension generation than in the magnitude of response for FS, and a significant increase in the time to maximal tension. Although there were no decreases in the magnitude of the responses to carbachol, KCl, or ATP, there were significant reductions in the rate of tension generation for carbachol and KCl and significant increases in the time to maximal tension for carbachol and ATP. Applying less tension over a wider area, the fascial collar provided a consistent and reproducible mild partial outlet obstruction.

Adenosine Triphosphate↗
PubMed1998

Effects of hypoxia, calcium, carbachol, atropine and tetrodotoxin on the filling of the in-vitro rabbit whole bladder.

PURPOSE: The urinary bladder stores urine at low intravesical pressure and empties the urine efficiently and completely. Bladder compliance is the property that allows the bladder to fill to near capacity without a large increase in intravesical pressure. The current study utilized an in vitro whole bladder model to determine the effects of hypoxia, alterations in extracellular calcium concentration, carbachol and atropine on bladder capacity and compliance. METHODS: Mature male New Zealand White rabbits were used in this study. The urinary bladder was excised from the rabbit together with a short segment of proximal urethra and mounted in a 400 ml. isolated bath containing Tyrode's buffer. Bladder filling was started by opening the bladder to a saline reservoir placed 80 cm. above the bladder. Intravesical pressure, rate of pressure increase, rate of volume increase, and maximal volume were digitally recorded. The bladder filling was repeated while the whole bladder was subjected to hypoxia, high calcium concentration, the presence of EGTA, carbachol, atropine and tetrodotoxin respectively. RESULTS: Results are summarized as follows: 1) Bladder filling was biphasic. There was an initial rapid rise in intravesical pressure followed by a slower rise. The final bladder volume averaged 46 ml. 2) Hypoxia significantly decreased the initial rate of the rise in intravesical pressure, increased the rate of bladder filling, and increased bladder volume by 43%. 3) Incubation of the bladder in the presence of EGTA also significantly decreased the initial rate of intravesical pressure rise, increased the rate of filling and increased bladder volume by 39%. 4) High concentrations of calcium increased the initial rate of rise in intravesical pressure. 5) Carbachol significantly increased the rate of intravesical pressure rise, decreased the rate of bladder filling, and decreased bladder volume. 6) Atropine and tetrodotoxin (TTX) had no effects on bladder filling. CONCLUSION: In summary, alterations in muscle tone had significant effects on bladder capacity and compliance.

Animals↗
PubMed1998

Effect of calcium and calcium chelator on the response of the bladder to in vitro ischaemia.

OBJECTIVE: To examine the effect of different concentrations of calcium on the contractile responses of isolated strips of rabbit bladder detrusor to various forms of stimulation after 2 h incubation in the presence of substrate and oxygen depletion (in vitro ischaemia), followed by 1 h of recovery. The resultant contractile responses were correlated with the level of lipid peroxidation as determined by malonedialdehyde (MDA) concentration. MATERIALS AND METHODS: Isolated strips of rabbit bladder detrusor smooth muscle were incubated in Tyrode's solution containing different concentrations of calcium (0-5.4 mmol/L). The effect of 2 h of incubation in oxygen- and substrate-free medium (in vitro ischaemia), followed by a 1-h incubation in the presence of oxygen and substrate, on the contractile responses to field stimulation, carbachol and KCl were determined. The effects of repetitive stimulation (15 s of stimulation at 32 Hz applied every 5 min during the 2-h experimental period) were also assessed. RESULTS: The contractile responses to all stimuli increased as the extracellular calcium concentration was increased from 0.6 to 5.4 mmol/L. A 2 h exposure to in vitro ischaemia, followed by a return to normal solution, resulted in a diminished response to all stimuli. This contractile dysfunction was least in the presence of calcium chelator (EGTA) and greatest in the presence of 5.4 mmol/L calcium. Repetitive stimulation during in vitro ischaemia also exacerbated the contractile dysfunction. Lipid peroxidation increased during in vitro ischaemia in proportion to the calcium concentration and was enhanced by repetitive stimulation during this period. Regardless of the incubation conditions, the reduction in the contractile response was significantly greater for field-stimulated tissues than for those stimulated with carbachol or KCl. CONCLUSIONS: These results show that the magnitude of contractile dysfunction induced by incubation in the presence of substrate and oxygen depletion is reduced in the presence of low calcium concentrations, increased in the presence of high calcium levels and increased in the presence of repetitive stimulation. In addition, the level of lipid peroxidation after the recovery period was proportional to the magnitude of contractile dysfunction present.

Animals↗