Effects of [1-desamino-8-D-arginine]vasopressin and papaverine on rabbit renal pelvis.

The effects of [1-desamino-8-D-arginine]vasopressin (DDAVP) (V2 receptor agonist) and papaverine on four continuous circular smooth muscle strips in rabbit renal pelvis were studied by an isometric tension recording methods. DDAVP suppressed spontaneous contractions in a dose-dependent and region-dependent way. Papaverine suppressed these contractions in a dose-dependent way simultaneously in all four portions. These results suggest that there may be distribution differences of V2 receptors in the renal pelvis. Together with its anti-diuretic action, DDAVP may merit consideration for the treatment of renal colic.

The effects of drugs on pacemaker regions of isolated rabbit renal pelvis.

Acetylcholine failed to change the frequency of spontaneous contractions in the proximal region of isolated rabbit renal pelvis, but significantly increased the contractile frequency in the middle and distal regions, which then reached similar levels to those of the proximal region. Pretreatment with reserpine caused a decrease in the frequency of spontaneous contractions in the proximal, but not in the middle or distal regions. Reserpine-pretreated tissues developed hypersensitivity to catecholamines, while acetylcholine produced effects similar to those observed in control preparations. Atropine and N-methyl-scopolamine antagonized the action of acetylcholine in both the middle and the distal regions, suggesting that the action was exerted through muscarinic receptors. Adrenaline and alpha-stimulating drugs, but not isoprenaline, significantly increased the contractile frequency of all three tissues: the increase in the proximal region reached levels in excess of its fundamental maximal frequency. Phentolamine caused a significant decrease in the frequency of the proximal region and fully inhibited the stimulating action of catecholamines, indicating that this stimulation was mediated by alpha-adrenoceptors. The myogenic nature of pacemaking cells was confirmed by the effect of tetrodotoxin, ouabain and verapamil. The decrease in frequency in the pacemaker region of the proximal pelvis whether caused by reserpine or phentolamine indicates a significant role of catecholamines in modulating pacemaker activity.

New method for direct stiffness measurement of the corpora cavernosa.

We describe a new methodology for direct ex vivo measurements of corporal stiffness. Using a new biosensor, stiffness of the corpora cavernosa was measured in 32 mature male Spraque Dawley rats. Mean stiffness (+/- se) value of the corpora was 8.186 +/- 0.318 gm/cm. The corpora was numerically the stiffest organ, when compared to the bladder and the prostate. Values measured at different points from both corpora showed a quite uniform stiffness (range 7.576-8.835 gm/cm). Hormonal stimulation with DHT was shown to significantly increase prostatic stiffness but not corpora stiffness. Similarly alpha-adrenergic antagonists did not affect corporal stiffness in a statistically significant manner. These results suggest that the influence of hormones and adrenergic stimulation on the passive properties of the corpora is negligible. It is concluded that this new method provides a reproducible new parameter for the measurement of corporal stiffness. It is anticipated that in the future this kind of stiffness measurement may be of use for the evaluation of the biomechanical properties of the corpora and its response to pharmacologic manipulation of the trabecular smooth muscle tone in vivo.

Resting and stress urethral pressures as a clinical guide to the mechanism of continence in the female patient.

Urethral closure pressures are examined with respect to continence and aging. An attempt is made to interpret the inherent orientation sensitivity of microtip transducer profilometry. The transmission of cough pressures along the length of the urethra is also examined, showing that incontinence is associated with low transmission.

Videomicroscopic imaging of ureteral peristaltic function in rats during cystometry.

Videomicroscopic imaging of the upper urinary tract was performed in 26 female anesthetized rats during bladder filling and micturition. Recordings were made of the pressure of the renal pelvis through a nephrostomy and visualization of the dynamics of the ureteral bolus. Peristaltic velocity, frequency, bolus length, and direction urine bolus propagation were derived on the basis of image processing using indigo carmine for contrast. In addition, nonstop cystometrograms were performed at an infusion rate of 0.22 ml/min characterizing bladder filling and micturition reflexes. Using this setup the pharmacological response of the upper and lower urinary tract dynamics to intravenous oxybutynin and LY274614 was evaluated and compared to observations made with placebo time controls. The data, obtained from the time controls, indicate that there is a significant time-dependent influence on the upper urinary function caused by the experimental methodology in the frequency of ureteral peristalsis and length of the bolus. Oxybutynin produced a significant increase in the length of the but not in the velocity of the bolus. LY274614 depressed pelvic pressure and ureteral frequency and increased bolus length. It is concluded that videomicroscopic imaging, in association with nonstop cystometry, provides a unique method to investigate the pharmacological effects of centrally and peripherally acting drugs on the upper and lower urinary tract function without mechanical manipulation of the ureter.

Rapid evaluation of the efficacy of pharmacologic agents and their analogs in enhancing bladder capacity and reducing the voiding frequency.

We report here the results of a simplified screening method to rapidly compare the pharmacologic action of drugs relevant to the urinary tract. This method avoids the use of anesthesia and of external infusion into the bladder relying on the physiological stimulation of the volume-evoked micturition reflex (VEMR) by diuresis. Mature female rats weighing 240-310 g were placed in restrainer cages that afforded access to food and water but limited movement. Under the rear of the rat, a collecting funnel and weight measuring device was secured. For each VEMR, the weight of the volume voided was recorded on a polygraph which also provided a record of the time of voiding. To evaluate the relative pharmacologic efficacy of the drug under study, 1 mg/kg furosemide along with the drug to be evaluated was diluted in 5 ml of saline and injected subcutaneously. Rats received approximately equimolar concentrations of thiphenamil and 15 other analogs, Ca2+ channel blockers, and K+ channel openers. The furosemide was given to obtain a controlled level of diuresis and avoid the effects of circadian variations in urine flow. Parameters considered were 1) mean volume voided per VEMR, 2) frequency, 3) output, and 4) latency. This model allows the rapid evaluation of drugs designed to increase bladder capacity and decrease the frequency of voiding, and it is particularly useful in evaluating the relative efficacy of drugs that are chemical analogs.

Age dependent response to exogenous estrogen on micturition, contractility and cholinergic receptors of the rat bladder.

The age related effects of 17beta-estradiol (E) supplementation on micturition and contractility of ovariectomized rats (OVX) were evaluated. Studies were carried out in young, 2 month, and mature, 10 month old rats which were distributed into three groups: Sham-operated (SHAM), (OVX), and (OVX+E). Following treatment, urodynamic studies were performed followed by an in vitro bladder tissue evaluation. Urodynamic studies show age and time related changes in bladder function. The in vitro results show that the hormone deprived tissues of 2 months old rats had a decreased responsiveness to cholinergic stimulation; maximum contractile force occurred at 78% and 187% for the SHAM. The response from the OVX+E tissues was evident at 113%. E supplementation of the mature rats increased bladder contractile force to the same levels as SHAM (156% and 176%). The response of the mature OVX rats remained significantly below that of SHAM or OVX+E rats. Findings suggest that the impact of E on bladder function depends on age at which it is given. Differential response between young and mature to exogenous E indicates that endogenous estrogen plays a major role in the neuromuscular development of normal bladder function and micturition reflexes. Contractility data show that OVX in young rats irreversibly decreases the response of the bladder to cholinergic stimulation, suggesting that exogenous E partially restores function while in mature rats, exogenous E was able to reverse the effects of OVX.

Dynamics of the upper urinary tract: II. The effect of variations of peristaltic frequency and bladder pressure on pyeloureteral pressure/flow relations.

The dynamics of pyeloureteral flow is described when there is no peristalsis and for peristalsis of high and intermediate frequencies, on the assumption that the ureter is uniform except in the mid-ureter and at the outlet. The possibility of upstream transmission of bladder pressure variations to the renal pelvis is considered. The overall behaviour depends on three principal variables, the maximum tube pressure in the contraction waves, the intrinsic peristaltic carrying capacity and the peristaltic frequency f, expressed in the form fT where T is the time for a peristaltic contraction wave to sweep through the ureter. At intermediate peristaltic frequencies (fT less than but comparable with one) oscillatory flow patterns can occur, in which periods of peristaltically driven flow alternate with extraperistaltic periods of flow through the open ureter. The kidney is better isolated from bladder pressure variations when the peristaltic frequency is high, but high peristaltic frequency can by itself lead to elevated renal pelvic pressure if the flow rate is high. Experimental observations in pigs are presented to support these conclusions.

Modeling of micturition characteristics based on prostatic stiffness modulation induced using hormones and adrenergic antagonists.

We present a biosensor intended to evaluate prostatic stiffness. The stiffness of the prostate was modulated using hormonal induction and adrenergic stimulation. The results show that the sensor can be sufficiently accurate to discriminate between soft prostates used as controls and those stiffened with hormones. The modulation produced by an adrenergic agent on prostatic stiffness was detected using this system. An electrical model was constructed embodying the parameters of prostatic stiffness, micturition frequency, and volume, demonstrating that prostatic stiffness correlates with micturition frequency.

Effects of artificial obstruction on the function of the upper urinary tract of Guinea pigs, rats and pigs.

PURPOSE: Four different experiments in animals were performed to evaluate the influence of pyelo-ureteral surgery on the function of the upper urinary tract. METHODS: Experiment I: In 17 female guinea pigs pyelo-ureteral anastomosis was performed microsurgically. Three months later, the ureteral peristalsis was investigated by measuring the intraureteral pressure and the in vitro activity of the renal pelvic and ureteric wall was analysed. Experiment II: 10 rats were used for microsurgical uretero-ureteral anastomosis. One month after surgery the pyelo-ureteral peristalsis was examined by videomicroscopy while simultaneously measuring the renal pelvic and intravesical pressure. Subsequently the kidneys were removed for histological examination. Experiment III: In 2 pigs unilateral pyeloplasty was performed. Using an implanted transmitter the intravesical and the renal pelvic pressures were recorded continuously over a time interval of 3 months. Five months after surgery the pyelo-ureteral peristalsis was investigated by pyelography. The kidneys were then removed for histological and biomechanical examinations. Experiment IV: A partial artificial obstruction was performed in 16 guinea pigs by implanting the ureter into the psoas muscle. Two to six months following surgery their upper urinary tracts were removed for analysis of in vitro activity as well as histological and immunohistochemical investigations of the ureter and renal pelvis. RESULTS: Experiment I: Ultrasound investigation showed in all cases a significant dilation of the renal pelvis. The ureteral contraction frequency distally was decreased in vivo as well as in vitro (p <0.05) compared with the controls. Experiment II: Videomicroscopic imaging showed in eight out of nine cases an interruption of the peristaltic wave below the anastomosis; the ureteral peristalsis was restored distally by ureteral contractions with a decreased frequency. Retroperistalsis was seen in the lower part of the ureter. The frequency of renal pelvic and ureteral contractions were decreased (p <0.05). Renal pelvic baseline pressure as well as contraction amplitude were irregularly changed. Histological examinations showed increased connective tissue within the renal pelvic wall in all cases. Experiment III: In both pigs an intermittent change in contraction frequency of the renal pelvis was found, associated with a changing contraction amplitude. Five months after surgery an interruption of the peristaltic wave was detected in both pigs. Histological examinations showed increased connective tissue within the renal pelvic wall. The stiffness of caliceal and pelvic tissue was lower following the pyeloplasty compared to the controls. Experiment IV: Following artificial partial ureteral obstruction in all guinea pigs the in vitro investigations showed an increased spontaneous activity of the upper urinary tract except in the proximal part of the ureter. Ureteral obstruction produced a change in contraction pattern of the proximal ureter and a decrease in contraction frequency of the distal ureter. Immunohistochemical investigations revealed rarefication and disorientation of nerve fibres within the proximal ureteric wall. CONCLUSIONS: Surgical interruption of the ureteral continuity and re-anastomosis cause a temporary disruption of the peristaltic wave at the anastomosis site. Ureteral peristalsis is restored by ureteral contractions associated with retroperistalsis as well as a decreased contraction frequency. Uretero-ureteral anastomosis in rats, pyelo-ureteral anastomosis in guinea pigs and pyeloplasty in pigs seem to influence the upper urinary tract similarly to a chronical functional obstruction, causing changes in pyelo-ureteral motility and spontaneous muscular activity of the renal pelvic and ureteral wall as well as biomechanical and histological characteristics.

Tactile resonance sensors in medicine.

Tactile sensors in general are used for measuring the physical parameters associated with contact between sensor and object. Tactile resonance sensors in particular are based on the principle of measuring the frequency shift, Deltaf, defined as the difference between a freely vibrating sensor resonance frequency and the resonance frequency measured when the sensor makes contact to an object. Deltaf is therefore related to the acoustic impedance of the object and can be used to characterize its material properties. In medicine, tactile resonance sensor systems have been developed for the detection of cancer, human ovum fertility, eye pressure and oedema. In 1992 a Japanese research group published a paper presenting a unique phase shift circuit to facilitate resonance measurements. In this review we summarize the current state-of-the-art of tactile resonance sensors in medicine based on the phase shift circuit and discuss the relevance of the measured parameters for clinical diagnosis. Future trends and applications enabled by this technology are also predicted.

Contractility of the pyeloureteral pacemaker system.

The patterns of mechanical contractility in the pyeloureteral pacemaker system were explored in an effort to identify some of the properties of initiating ureteral peristalsis. Rabbit renal pelvises were studied in vivo, in vitro perfused with Krebs solution through the renal artery and in segments. The results show that all segments of renal pelvic smooth muscle are capable of spontaneous contractions, the fornix having the highest frequency with respect to the pelvis. It is also demonstrated that the pelvic contractile wave concentrically accelerates along the renal pelvic perimeter. Under steady state conditions, renal pelvic pressure undergoes a low frequency oscillation having a period of 1--2 min which is flow-rate dependent. The results are discussed within the context of the pyeloureteral pacemaker system and the possible existence of a feedback mechanisms between the renal pelvis and the perfusion of the kidney.

Velocity gradient and contraction frequency of the pyeloureteral system.

An optical detection method, using video imaging, is used to quantitatively record the frequency and velocity profile of the renal pelvis of the rabbit. It is demonstrated that concentric waves originating at the periphery of the pelvis have an initial velocity of 3.2 cm/sec, accelerating toward the pelviureteral junction reaching a final velocity of 6.4 cm/sec.

Influence of hormone treatment on prostate growth and micturition characteristics of the rat.

The influence of dihydrotestosterone propionate (DHT) and estradiol (E) on prostate growth and micturition was evaluated. Complete studies were carried out on 49 Sprague-Dawley rats over a 14-day period. Rats were divided into three groups: (1) controls, (2) DHT, and (3) DHT + E. All groups were injected daily with 0.1 ml of sesame oil, together with 1.25 mg/kg of DHT for group 2 and 1.25 DHT + 0.125 mg/kg E for group 3. Physiological measurements of micturition were done weekly by subcutaneously administering a fluid loading dose consisting of 10 mg/kg furosemide + 5 ml saline. Parameters of micturition frequency, volume, and prostate weight were calculated. Prostate weight values for controls were 0.89 +/- 0.06 g while those treated with DHT increased significantly to 1.26 +/- 0.10 g (P < 0.05) and those treated with DHT + E also increased significantly to 1.24 +/- 0.09 g (P < 0.05). There was no significant difference in prostate weight between the DHT and DHT + E groups. Analysis of micturition data shows that the mean volume voided per micturition decreases in both the DHT and DHT + E treated rats. At between 7 and 14 days of DHT and DHT + E treatment, rats micturated at significantly reduced mean volumes. The lowest mean volume per micturition was detected on the 14th day of DHT treatment, showing a significant reduction from control values of 3.05 +/- 0.27 to 1.68 +/- 0.05 ml. The corresponding value of the mean micturated volume in the DHT + E groups was 1.86 +/- 0.31 ml. Control values for frequency of micturition was 3.25 +/- 0.52/hr, while for rats treated with DHT it was 3.62 +/- 0.38/hr and for DHT + E it was 4.0 +/- 0.54/hr. Evidence is provided to demonstrate that 14 day DHT, and particularly DHT + E, stimulation produces significant alterations in prostate weight and micturition characteristics of unanesthetized rats. On the basis of these observations it is proposed that the hormonally enlarged prostate promotes stimuli to trigger the spinal micturition reflex, thereby producing increased frequency of micturition.

Statistical properties of the temporal and spatial distribution of interperistaltic intervals and their relationship to pacemaker and respiratory rhythmicity.

A straightforward method is outlined for the presentation of the temporal and spatial characteristics of interperistaltic intervals obtained from the canine ureter. The fundamental statistical property of ureteral peristaltic contractions is demonstrated to be multimodal. This is characterized by a basic rate and whole number multiples of that rate. The methods for identifying the relationship of peristalsis with the pacemaker and respiratory rate is outlined.

Relaxant effect of thiphenamil HCl on upper urinary tract frequency of contraction of healthy asymptomatic volunteers.

The pharmacologic effect of thiphenamil HCl on the upper urinary tract as a relaxant of renal pelvic contractions was studied. A total of 17 subjects with no known upper urinary tract abnormalities were scanned. A Diasonics ultrasound scanner at 3.5 MHz was used to visualize the kidney and renal pelvis with the subject in the supine position. Control recordings of renal pelvic and calyceal contractility were made on videotape for approximately 30 min. The subject was then given a single dose of 400 mg thiphenamil HCl and visualization of contractility continued for approximately 60-90 min. Criteria for the evaluation of the data were the mean frequency of pelvic contraction cross-section of the pelvis, and velocity and direction contraction. Ultrasonic images were filtered by a video filtering process and averaged using the digital conversion and summation in real time. The results show that under control conditions renal pelvic contractions are at a frequency of 2 +/- 1.8 min-1. Contractions are initiated with the intrarenal pelvis and continue towards the ureter at a rate of 1.3 +/- 0.8 cm/s. Following thiphenamil HCl, there is a significant reduction in pelvic contraction frequency, 0.6 +/- 0.6 min-1, and the opposing walls of the renal pelvis do not completely close in the formation of a bolus. The results obtained from this study demonstrate that thiphenamil suppresses upper urinary tract contractility. As a consequence of this observation, it is postulated that this agent may be of use in the acute relaxation of the upper urinary tract for renal colic and stone management.

Pharmacologic treatment of detrusor incontinence with thiphenamil HCl.

A controlled double-blind crossover study is reported in which quantitative urodynamic data and qualitative information are combined to evaluate the treatment of detrusor incontinence using thiphenamil HCl in patients with detrusor instability. Patients placed on the treatment protocol were randomized to placebo or thiphenamil 400 mg q.i.d. Two weeks of thiphenamil HCl or placebo administration were followed by 1 week of washout followed by a cross-over to an additional 2 weeks of placebo or thiphenamil HCl administration. Of the 23 patients 7 dropped out at various stages of the study. The mean age of patients studied was 44 +/- 14 years old. Throughout the study, patients were asked to complete a formalized diary card of the amount and time of voiding and the incidence of incontinence. Three urodynamics studies were done in the following sequence: pretreatment, postwashout, and posttreatment. Parameters of bladder capacity, sensations, stability and pressure/flow were obtained. In addition, resting urethral closure pressures were recorded. The results show that the frequency of incontinence, which was based on the patients' responses, decreased significantly (0.01 less than p less than 0.025). There was an insignificant decrease in the number of voidings and increase in the amount voided each time. Patients on thiphenamil reported that their pads were significantly drier from baseline (p = 0.01). In response to questions comparing problems caused by urine loss during baseline and thiphenamil treatment, analysis shows a significant decrease of problems due to loss of urine (p = 0.01) when the patient was taking the drug compared to the placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacologic effect of thiphenamil HCl on lower urinary tract function of healthy asymptomatic volunteers.

The effect of thiphenamil HCl on the urodynamic parameters of bladder filling, voiding and isometric contraction was examined in controls. Data were obtained from 25 control female subjects with a mean age of 27.6 +/- 6.6 years. Three urodynamic studies were done on each subject on 3 different days. These studies were: (1) control study, (2) drug study with a single oral dose of 400 mg thiphenamil HCl and (3) another with 800 mg. Each urodynamic study involved filling and voiding cystometrograms to characterize stability, sensations of fullness and urgency, bladder capacity, urethral opening pressure, maximum flow rate, maximum detrusor pressure and residual urine. In addition, isometric detrusor pressure measurements were made at bladder volume increments of 100 ml. Each urodynamic study was done in the sitting position using medium fill water cystometry at 20 ml/min. Isometric pressures were made by catheterizing the subject with an 18-french three-way Foley catheter with a 30-ml balloon. One lumen was used to fill the bladder and the second to measure pressure. The results show that bladder capacity and the volume at which sensations of fullness and urgency are expressed are not significantly changed under the influence of thiphenamil HCl. Significant differences were seen in the maximum pressure generated by the detrusor during voiding and in the maximum urine flow rate. These differences were most pronounced at the 800-mg thiphenamil HCl dose. The isometric data show a highly significant increase in the maximum isometric pressure developed at the low bladder volumes.(ABSTRACT TRUNCATED AT 250 WORDS)

Pyeloureteral dynamics in the intact and chronically obstructed multicalyceal kidney.

The transport of urine in the upper urinary tract of the multicalyceal kidney was studied in healthy and chronically obstructed pigs in terms of renal pelvic pressure, rate of and coordination of ureteral contractions, and bolus volume. The variations of these parameters to diuresis was examined by incremental elevation of urine output effected by intravenous infusion of mannitol. In 16 healthy animals the mean variation in urine flow was 0.01-3.20 ml/min, the change in peristaltic rate ranged from 0.763 to 5.125 min-1, and bolus volume from 0.003 to 2.083 ml.. In 14 chronically obstructed kidneys, for a mean variation in urine flow of 0.006-5.4 ml/min, peristaltic rate ranged from 0.237 to 6.095 min-1 and bolus volume from 0.00 to 1.80 ml. Discoordinated contractions, bursts of peristalsis, and incompletely transmitted pelvic contractions were characteristic of a chronically obstructed system. These observations are compared with the unobstructed unicalyceal and multicalyceal kidney. The disrupting impact of chronic ureteral obstruction on the hierarchical organization of the pyeloureteral pacemaker system is discussed.