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Biomedical subjects

R van Mastrigt

Publications and source records attributed to R van Mastrigt.

At least 19 recordsLinked to original sources

Shortening induced effects on force (re)development in pig urinary smooth muscle.

INTRODUCTION: When muscle is allowed to shorten during an active contraction, the maximum force that redevelops after shortening is smaller than the isometric force at the same muscle length without prior shortening. We studied the course of force redevelopment after shortening in smooth muscle to unravel the mechanism responsible for this deactivation. METHOD: In a first series of measurements the shortening velocity was varied resulting in different shortening amplitudes. In a second series, the duration of stimulation before shortening (shortening delay) was varied. In a third series, the stimulation was interrupted for a certain duration immediately after shortening. Force, muscle length and stimulation were continuously recorded. Time constants were calculated to describe the rate of force development before and after shortening. RESULTS: With increasing shortening amplitude and with increasing shortening delay, force redevelopment decreased. Redevelopment increased with an increase in the interruption time. After stimulus interruption force redeveloped mono-exponentially with a time constant similar to that of isometric contractions (approximately 3s). Without the interruption of stimulation, the redevelopment of force immediately after shortening was best described by two time constants; one similar to and one about 3-5 times faster than the isometric time constant. DISCUSSION: Force (re)development is caused by a cascade of events leading to the cycling of cross-bridges. In smooth muscle, isometric force development is described by a time constant of about 3s. Force redevelopment immediately after shortening involves a second process which takes place at a faster rate (time constant about 1s). We assume that this process is faster due to the immediate availability of cytoplasmic calcium released during active shortening. Deactivation presumably is caused by disorganization of filaments during shortening.

Animals↗

Contractile properties of the proximal urethra and bladder in female pig: morphology and function.

AIMS: To compare the contractile properties of proximal urethral and bladder muscle of the female pig. MATERIALS AND METHODS: In two proximal segments (I and II) of the urethra, small muscle bundles were excised to measure the force-length (maximum force) and the force-velocity (unloaded shortening velocity) relation using the stop-test. The rate of force development was calculated using phase plots. Contractile properties of urethral and bladder segments were statistically compared using the Mann-Whitney U-test. Immunohistochemical staining of whole circumference urethral cross sections was used to identify the location of smooth and striated muscle fibres. RESULTS: On isometric force development, the urethral muscle bundles revealed a fast ( approximately 0.5 sec) and a slow ( approximately 2.1 sec) time constant, whereas in bladder only a slow ( approximately 2.3 sec) component was measured. On average, isometric force was highest in bladder. The length range over which force was produced was smallest in urethral segment II, followed by urethral segment I and finally bladder. The unloaded shortening velocity was 0.15, 0.25 and 0.35 1/sec, respectively. Histological preparations showed that smooth as well as striated muscle was present in proximal urethra. In urethral muscle bundles, spontaneous contractions were measured with a frequency of 0.4 Hz. CONCLUSIONS: Differences in contractility found between urethra and bladder may be ascribed to the presence of striated muscle in the proximal urethra. The regulation of tone and spontaneous contractions may be part of the continence mechanism in the female pig urinary tract.

Actins↗

Bladder volume sensitivity of isovolumetric intravesical pressure.

AIMS: Recently, methods have been introduced for non-invasively measuring the isovolumetric bladder pressure. This pressure can also be measured invasively using a stop test. In itself, the isovolumetric pressure is a measure of urinary bladder contractility, by combining it with maximum urinary flow rate it can be used to diagnose infravesical obstruction. We have studied the (possible) volume dependence of this pressure in order to enhance the accuracy of this type of measurements and to explore its physiological background and possible diagnostic relevance. MATERIALS AND METHODS: In 1,020 healthy subjects, recruited for an ongoing longitudinal study of changes in bladder contractility secondary to prostatic enlargement, we measured the isovolumetric bladder pressure using the condom catheter method. In each subject, voiding was repeatedly interrupted. The resulting pressure-volume relations were normalized and averaged. RESULTS AND CONCLUSIONS: There is an optimum bladder volume for isovolumetric pressure measurements, averaging 264 +/- 122 ml (mean +/- SD). Measurements should be taken at or above the optimum volume. At volumes below the optimum volume, the pressure decreases by approximately 5% for each 10% of volume decrease. At bladder volumes smaller than 247 ml pressure readings in 50% of subjects are suboptimal. The optimum volume for isovolumetric pressure generation is only marginally related to voiding diary parameters. Probably it represents mechanical properties of the bladder, whereas voiding diary parameters more likely represent neurophysiological properties. However, the optimum volume does not reflect the optimum (smooth) muscle length for force generation of the bladder wall: during normal voiding bladder smooth muscle always operates at a suboptimal length for force generation.

Adult↗

Epidemiological aspects of recruitment of male volunteers for non-invasive urodynamics.

INTRODUCTION: We studied epidemiological aspects of recruitment of volunteers for a non-invasive urodynamic study. MATERIALS AND METHODS: 9,236 volunteers were invited by 20 general practitioners (GPs), using two different recruitment methods, i.e. by mail only, or during a subsequent visit to the GP's office. Factors influencing the response rates were analyzed. We also tested how much the recruited population of volunteers differed from the general population, by comparing it to another, proven representative study carried out earlier in 1,662 subjects. RESULTS: In the recruited population the prostate volumes were not significantly different from the proven representative study, but the symptom score was statistically significantly higher, although the difference was so small it may be called clinically irrelevant. Recruitment of volunteers in two steps, i.e. asking them first to visit the GP's office, and inviting them there to visit the outpatient clinic, rather than directly inviting them (in writing) to the clinic seemed to lead to a higher response, although this effect could not be statistically discriminated from the difference in response rates between GPs. CONCLUSION: The population recruited was not urologically different from the general population. The response depended on age, being highest around the age of 60, and increased with social economic status. It also depended on the GP who recruited the subjects, and/or on the recruitment method.

Adult↗

Contractile properties of inner and outer smooth muscle bundles from pig urinary detrusor.

Like in the human detrusor, the pig urinary detrusor muscle consists of two layers: compactly arranged smooth muscle bundles on the mucosal side (inner layer) and loosely arranged smooth muscle bundles on the serosal side (outer layer). The contractile properties of muscle bundles of both layers were measured using the stop test followed by an isometric contraction. Total and passive forces were measured in ten muscle bundles from the inner and outer muscle layers. Active force was defined as the difference between total and passive force. The curvature and the unloaded shortening velocity of the force-velocity relation were calculated from the shortening forces measured during the stop test. The rate of force development was calculated from the isometric contraction. Differences in contractile properties between both layers were pairwise tested using the Wilcoxon Signed Ranks test. Percentage wise, the outer layer muscle bundles produced the highest active isometric force. The shortening forces were also higher in the outer layer bundles. As a result, both the curvature and the unloaded shortening velocity, derived from the average force-velocity relations fitted to the data sets, were higher in the muscle bundles from this layer. Finally, the outer layer muscle bundles contracted significantly faster than those of the inner layer. Muscle bundles from the outer layer of pig detrusor were found to be faster and stronger (more phasic) than the weaker and slower (more tonic) bundles from the inner layer, suggesting that during bladder contraction the outer layer of the detrusor does more work than the inner layer.

Animals↗

Correlation of non-invasive urodynamics with International Prostate Symptom Score (IPSS) and prostate volume.

AIM: To study the correlation between non-invasive urodynamic data, the International Prostate Symptom Score (IPSS) and the prostate volume. MATERIALS AND METHODS: Data of 667 healthy volunteers participating in a longitudinal study of changes in urinary bladder contractility secondary to BPE were analyzed. The prostate volume was assessed by transabdominal ultrasonography. Uroflowmetry followed to verify if a minimum free flow rate of 4.5 ml/sec could be achieved. While (re)filling the bladder by drinking, the subjects completed the Dutch version of the IPSS. Next, the bladder pressure was non-invasively measured using the condom catheter method. The urethral resistance (URR) was calculated from the maximum condom pressure and the maximum free flow rate. RESULTS: The IPSS ranged from 0 to 29, (6.1 +/- 4.8) (mean +/- SD), whereas the prostate volumes ranged from 8 to 140 cm3, (34 +/- 18). Twenty eight percent (185/667) of the subjects had a non-invasively quantified high URR and a significantly higher IPSS (7.3 +/- 5.2) than those with a low URR (IPSS (5.7 +/- 4.6)), Mann-Whitney U-test: P < 0.001. The IPSS and the URR were significantly correlated, Spearman's rho (rho) = 0.20, P < 0.001. A significant difference between the prostate volumes, 36 +/- 21 cm3 in the high URR versus 33 +/- 17 cm3 in the low URR group, was not found, P = 0.18. CONCLUSIONS: A weak though statistically significant correlation was found between the non-invasively quantified URR and the IPSS. This suggests that an elevated resistance is a necessary, but not a sufficient condition for lower urinary tract symptoms (LUTS). No correlation was found between the URR and the prostate volume.

Adult↗

Comparison of repeatability of non-invasive and invasive urodynamics.

AIMS: We have developed a method for the non-invasive measurement of urinary bladder pressure, and we apply this method in a longitudinal study of changes in bladder contractility in response to prostatic enlargement. In each volunteer in this study, we measure the bladder pressure twice. In the present study we have used this data to compare the repeatability of the non-invasive method to that of pressure-flow studies in a comparable population of patients. METHODS: Difference plots were made of non-invasive bladder pressure measurements in 457 volunteers and of pressure-flow studies in a comparable population of 397 male patients. To compare the repeatability of two different methods for clinical measurement, the standard deviation of differences between repeated measurements in one individual needs to be normalised. Often a normalisation by dividing by the mean is done. We show that that normalisation may lead to erroneous results. We have normalised the standard deviations by dividing by the difference between the 97.5th and 2.5th percentile of the mean of the two observations in each subject. RESULTS: Normalised repeatability of the non-invasive method was 0.15, that of the various parameters derived from the pressure-flow studies varied from 0.11 to 0.22. CONCLUSIONS: We conclude that the repeatability of the tested non-invasive urodynamic method is comparable to, or slightly better than, that of pressure-flow studies. We further conclude that normalising standard deviations of differences by dividing by the difference between the 97.5th and 2.5th percentile of the mean is a suitable method to compare the repeatability of different methods for clinical measurement.

Adult↗

Prostate volume ultrasonography: the influence of transabdominal versus transrectal approach, device type and operator.

OBJECTIVES: We conduct a longitudinal non-invasive study of changes in urinary bladder contractility secondary to benign prostatic enlargement. In that study, the prostate volume is estimated by transabdominal ultrasonography. The accuracy of those measurements was verified by comparison of transabdominal to transrectal stepwise planimetric ultrasonography as the gold standard. Also, two different transabdominal devices used were compared, and the influence of different operators was studied. MATERIALS & METHODS: Two series of measurements in 100 patients each were done. In the first series, transabdominal and transrectal sonography were pairwise compared in each patient. In the second series, transabdominal measurements were done with two devices (a hospital Aloka SSD-1700 and a portable Aloka SSD-900). Transrectal scannings were done by three investigators whilst all transabdominal scannings were done by one. Regression graphs, ratio plots and statistical analyses of the data quantified the reproducibility of different methods, observers and device types. RESULTS: In the transrectal-transabdominal series of prostate volume measurements (in cm3), the Pearson correlation coefficient was 0.84 (p < 0.001), the mean of the means was 51.8 +/- 23.0 (mean +/- S.D.), and the mean of the differences was 1.0 +/- 1.4. In the series with two devices, the Pearson correlation coefficient was 0.73 (p < 0.001), the mean of the means was 31.0 +/- 10.9, and the mean of the differences was 1.0 +/- 1.3. CONCLUSION: No statistically significant differences were found between the transabdominal- transrectal ultrasonography, two different transabdominal devices nor between different observers. However, for those using these measurements in everyday clinical practice, it is worth to point out that in our data a transabdominal scan and a transrectal scan in the same patient, on the same day, differed more than 30% in one fourth of the patients and that two transabdominal scans in the same patient (with two different devices, on two different days) differed more than 30% in every fifth patient.

Body Weights and Measures↗

Pathophysiological aspects of bladder dysfunction: a new hypothesis for the prevention of 'prostatic' symptoms.

This article reviews the literature on the pathophysiology of male lower urinary tract symptoms (LUTS) with the intention of developing a new preventive intervention for this bothersome disease. Traditionally, male voiding dysfunction has been thought to arise from bladder outlet obstruction (BOO) caused by prostatic enlargement. Many years of research, however, have shown that a clear relationship between the size of the prostate and the occurrence or severity of symptoms is doubtful. Because of its crucial role in urination, it is increasingly being accepted that the clinical manifestation of voiding dysfunction relies on the functional behaviour of the bladder. Several animal studies have shown that bladder performance can be improved by increasing urine output. Contrary to alterations observed in pathologic situations, an increased urine output provides a physiologic stimulus for animal bladder function improvement. We hypothesise that a trained bladder should be less susceptible to the harmful effects of ageing and obstruction. Future symptoms may thus be prevented. In humans an increased urine output can be achieved by drinking additional water, which could be an adequate preventive intervention.

Aging↗

Applicability and reproducibility of condom catheter method for measuring isovolumetric bladder pressure.

OBJECTIVES: To report on the applicability, reproducibility, and adverse events of the noninvasive condom catheter method in the first 730 subjects of a longitudinal survey of changes in urinary bladder contractility secondary to benign prostatic hyperplasia, in which 1300 men will be evaluated three times in 5 years using this method. METHODS: Subjects were recruited by general practitioners, general publicity, and e-mail. Only those meeting the study criteria were entered in the study. If the free flow rate exceeded 5.4 mL/s, at least two consecutive condom pressure measurements were attempted using the condom catheter method. The condom pressure measured reflected the isovolumetric bladder pressure, a measure of urinary bladder contractility. The reproducibility of the method was quantified by a difference plot of the two maximal condom pressures measured in each subject. RESULTS: In 618 (94%) of 659 eligible participants, one condom pressure measurement was completed; two measurements were done in 555 (84%). The maximal condom pressure ranged from 28 to 228 cm H2O (overall mean 101, SD 34). A difference between the two pressures of less than +/-21 cm H2O was found in 80%. The mean difference was -1 cm H2O (SD 18), significantly different from 0. Some adverse events such as terminal self-limiting hematuria were encountered. CONCLUSIONS: The condom catheter method is very suitable for large-scale use. It has a success rate of 94% and a reproducibility comparable to that of invasive pressure flow studies.

Condoms↗

Development of a non-invasive strategy to classify bladder outlet obstruction in male patients with LUTS.

To diagnose bladder outlet obstruction in male patients with lower urinary tract symptoms (LUTS), it is necessary to measure the bladder pressure via a transurethral (or suprapubic) catheter. This procedure incurs some risk of urinary tract infection and urethral trauma and is sometimes painful to the patient. We developed an external condom catheter to measure non-invasively the bladder pressure and developed a strategy to classify bladder outlet obstruction (BOO) based on this measurement. Seventy-five patients with a wide range of urological diagnoses underwent a pressure-flow study followed by a non-invasive study. We tested five different strategies to classify the patients using the provisional International Continence Society (ICS) method for definition of obstruction as the gold standard. Leakage of the external catheter occurred in eight (40%) of the first 20 tested patients. In the remaining 55 patients, only five (9%) of the measurements failed because of leakage. Of the 75 patients, 56 were successfully tested non-invasively. According to the ICS nomogram, the PFS showed that 22 of these patients were non-obstructed, 12 patients were equivocal, and 22 patients were obstructed. Ten of these 56 patients strained, and we found that the relatively high abdominal pressures in these patients were not reflected in the externally measured bladder pressure. Of the remaining 46 patients, 12 of 13 non-obstructed patients and 30 of 33 combined equivocal and obstructed patients could be correctly classified. We developed a simple, non-invasive classification strategy to identify BOO in those male patients who did not strain during voiding.

Catheterization↗

Development of a low-cost flow meter to grade the maximum flow rate.

We developed an inexpensive flow meter to grade the maximum flow rate of individuals at locations other than the clinical setting. This flow meter consists of a funnel connected to a collecting tube with several exit ports. Urine directed into this tube flows through one or more ports and is collected in a measuring cup to measure the voided volume. The number of ports emitting the liquid is a measure for the flow rate. We made four experimental models to test and compare some of the physical properties. One of these models was selected as a prototype and was tested in five healthy volunteers. All volunteers voided repeatedly in a standard rotating disk flow meter and in this prototype to test its accuracy. The response time of the experimental models depended on the outlet resistance of the exit ports and the volume of the collecting tube. In two models, this time was comparable with that of currently used volume-based electronic flow meters (approximately 2 seconds). In healthy volunteers, the maximum flow rates graded with the selected prototype and those measured with the rotating disk flow meter showed good agreement (difference=0.4+/-2.6 mL/s; mean+/-SD). The low-cost flow meter may be used repeatedly to grade the maximum flow rate at private and familiar locations (for example, at home), which may increase the accuracy of evaluating the urinary stream in patients with lower urinary tract symptoms.

Adult↗

Mechanical properties of (urinary bladder) smooth muscle.

This short overview of the mechanical properties of smooth muscle focusses on the force-velocity relation of (mainly pig urinary bladder) smooth muscle, and its dependence on the length of the muscle and its degree of activation. Also the response of the muscle to length and force changes at a rate beyond the physiological range is discussed. The force-velocity relation of this type of muscle can be approximated by the hyperbolic Hill equation, with a normalised maximum shortening velocity in the order of 0.25 muscle lengths/s. As in striated muscle, the maximum isometric force depends on the stretched muscle length and shows a maximum at a certain length. Interestingly, smooth muscle does not normally seem to operate at this length, but far below it. Both the isometric force and the unloaded shortening velocity depend on the degree of activation of the muscle, and so does the 'curvature' of the Hill equation. The series elasticity of the muscle, which can be measured by applying length changes at a rate beyond the physiological shortening velocity, is found partly in the cross-bridges, and partly external to these. An isometric quick release of 4-10% of the muscle length is necessary to remove all tension, depending on the total force exerted by the muscle. Force recovery after such a release is biexponential in a 700 ms window. The slowest component of this recovery, with a time constant in the order of 0.45 s is mainly associated with cycling of the cross-bridges, the fastest with the external series (visco)elasticity. Isometric force development has a time constant in the order of 3 s. indicating that excitation-contraction coupling rather than cross-bridge cycling is rate limiting in this process.

Animals↗

Urodynamic follow-up of experimental urethral obstruction in individual guinea pigs.

It is unknown whether changes in bladder function due to urethral obstruction follow a specific sequence. To answer this, we adapted a small animal model to allow repeated complete pressure-flow studies, enabling individual follow-up of changes in bladder function on urethral obstruction. Obstruction was induced in guinea pigs by placing a silver ring around the urethra. Urodynamic studies were repeated under anesthesia with ketamine/xylazine. Bladders were filled and bladder pressure measured through a single suprapubic catheter. Urine flow rate was measured using an ultrasound probe around the penis. Accurate measurements of bladder pressure and urine flow rates were obtained at 1-week intervals for 11 weeks in individual guinea pigs. In the control animals, the urodynamic parameters did not show significant changes. In the obstructed group, urethral resistance (P(low,ave)) increased from 20 to 35 cm H(2)O after 4 weeks and remained at that level. The maximum flow rate (Q(max)) increased from 0.17 to 0.24 mL/s after 2 to 3 weeks. After this peak, it gradually decreased to lower than the starting value after 10 to 11 weeks. The pressure at maximum flow rate (p(Qmax)) increased from 24 to 47 cm H(2)O after 6 to 7 weeks and thereafter declined. During weeks 1 through 4 of obstruction, unstable contractions were seen. All animals followed a similar sequence of patterns but at variable rates. Our animal model allows complete urodynamic follow-up of individual animals with urethral obstruction. We observed a specific sequence of changes in urodynamic patterns and parameters of bladder function.

Animals↗

Length dependence of the contractility of pig detrusor smooth muscle fibres.

Evidence on the length dependence of the contraction velocity of smooth muscle fibres is contradictory. Nevertheless, a thorough understanding of this dependence is essential for a correct urodynamic diagnosis of voiding problems. We studied muscle fibres of pig urinary bladders (n = 23). Force-velocity relations were measured at different muscle lengths with a stop test technique. This method involves measuring force generation of electrically stimulated muscle fibres during controlled shortening from a pre-shortening length at a pre-set velocity to a fixed stop-length. We normalized the length dependence of the measured properties to slack length, optimum length (the length at maximum isometric force generation), and passive force. Isometric force was found to be length dependent with an optimum length of 290+/-68% of the slack length (n = 11, P < 0.05). The maximum shortening velocity was 0.37+/-0.14 s(-1) related to the slack length and 0.13+/-0.05 s(-1) related to the optimum length and was not length dependent (n = 16, P < 0.05). Slack length is preferable to normalize the length dependence of smooth muscle.

Animals↗