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M S Damaser

Publications and source records attributed to M S Damaser.

29 records · Page 2Linked to original sources

Partial bladder outlet obstruction in the fetal rabbit.

PURPOSE: We developed and tested an animal model of bladder dysfunction due to posterior urethral valves using partial outlet obstruction of the fetal rabbit bladder. MATERIALS AND METHODS: Partial bladder outlet obstruction of fetal rabbit bladders was created on day 23 of gestation. Of the litter of 8 to 10 fetuses half was obstructed and the remainder served as controls. The doe and fetuses were sacrificed on day 30 of gestation (full term 31 to 32 days) and the fetal bladders were removed. Bladders that had doubled in weight from the average bladder weight of the control littermates were deemed sufficiently obstructed. Hematoxylin and eosin staining was performed and bladder strip response to 32 Hz. field stimulation, 200 microM. bethanechol and 200 mM. potassium chloride was measured. RESULTS: Average body weight did not differ between the control and obstructed fetuses, indicating that surgery did not hinder fetal development. Hematoxylin and eosin staining confirmed smooth muscle cell hypertrophy and increased connective tissue in the obstructed bladders. Obstructed bladder strips responded significantly less to field stimulation, and significantly more to bethanechol and potassium chloride (mean plus or minus standard deviation 5.18 +/- 1.52, 6.29 +/- 1.3 and 10.15 +/- 2.18 x force per/100 mg. tissue, respectively)than control bladder strips (9.0 +/- 1.19, 3.5 +/- 0.46 and 6.16 +/- 1.33 x force per/100 mg. tissue, respectively) suggesting that denervation supersensitivity may have resulted from obstruction. CONCLUSIONS: Partial outlet obstruction of the fetal rabbit bladder results in bladder hypertrophy and dysfunction but these changes are markedly different from those in the adult rabbit. Since rabbit fetal development is delayed compared to human fetal development, this model can be used to assess the consequences of posterior urethral valves.

Animals↗

Calcium regulation of urinary bladder function.

PURPOSE: To investigate the effect of independently inhibiting calcium influx from extracellular sources and calcium release from intracellular stores on the ability of the urinary bladder to generate pressure and empty. MATERIALS AND METHODS: Rabbit bladders were mounted in an in vitro whole organ bath and filled with 15 ml. saline. Each bladder was incubated separately in Tyrode's solution, with diltiazem (10 microM), to block extracellular calcium influx, or with thapsigargin (40 microM) and ryanodine (80 microM), to block the uptake and release of calcium from the sarcoplasmic reticulum. The bladder was then stimulated isometrically with field stimulation (32 Hz), and to empty with field stimulation and with bethanechol (250 microM), independently. During stimulation, transmural pressure and volume emptied were measured. From these, flow rate, power, and external mechanical work were calculated. RESULTS: In the presence of diltiazem, the time to maximal pressure decreased while the rate of pressure generation increased. This results from increased participation of intracellular calcium release, which occurs rapidly and near the smooth muscle filaments, decreasing the diffusion time. In the presence of thapsigargin and ryanodine the maximal rate of pressure generation was decreased, due to the increased diffusion time required for calcium to move to the muscle filaments from extracellular sites. CONCLUSIONS: The current study demonstrates that bladder pressure generation and emptying are dependent upon both an influx of calcium through L-type calcium channels (inhibited by diltiazem) and the stimulated release of calcium from the SR (inhibited by thapsigargin and ryanodine).

Animals↗

Etiology of bladder dysfunction secondary to partial outlet obstruction. Calcium disregulation in bladder power generation and the ability to perform work.

Similar to all smooth muscle, contraction of urinary bladder smooth muscle depends upon a rise in intracellular free calcium, which results from both calcium influx from extracellular spaces and calcium release from intracellular stores (calcium-induced calcium release [CICR]). Recent studies from our laboratory demonstrate that one of the major dysfunctions induced by partial outlet obstruction is a marked reduction in the participation of CICR (from IP3-sensitive and IP3-insensitive sites on the sarcoplasmic reticulum [SR]) during stimulation by both field stimulation (neurotransmitter release) and by direct muscarinic stimulation (bethanechol). Experimentally, rabbit urinary bladder function can be evaluated using an isolated whole bladder model. The current study utilizes the isolated whole bladder model to compare the effects of partial outlet obstruction on the responses to field stimulation and bethanechol with the responses of normal bladders following inhibition of CICR with the combination of thapsigargin+ryanodine. The parameters measured include the magnitude of pressure generation, rate of pressure generation, time to maximal pressure generation, percent volume emptied, rate of emptying, power generation, and work performed (both total work and work per ml emptied). Partial outlet obstruction resulted in virtually identical alterations in the responses of the bladder to stimulation (field stimulation and bethanechol) to that of inhibition of CICR by thapsigargin+ryanodine. Thus, these studies provide strong support for our hypothesis that the contractile dysfunctions secondary to partial outlet obstruction are directly related to a marked inhibition of the CICR component of the response to both field stimulation and bethanechol.

Animals↗

Partial outlet obstruction induces chronic distension and increased stiffness of rat urinary bladder.

In order to identify the passive properties of the bladder during filling, we measured cystometrograms (CMGs) of rat urinary bladders that had been outlet obstructed for 6 weeks and age-matched controls in conscious, unrestrained animals and in fully relaxed whole bladders in an organ bath. In the organ bath, each bladder was allowed to empty passively at zero transmural pressure. The volume remaining was labelled zero pressure volume (ZPV) and was used as the reference volume to normalize contained volume, deriving wall stretch. Increased ZPV implies that the bladder contains more urine at low stresses and therefore is more distended. In awake animals, the obstructed bladder CMGs showed spontaneous contractions. The pressures between contractions were similar to those in CMGs performed in the organ bath, suggesting that passive properties determine the minimum pressures during filling in vivo. The ZPV of the obstructed and control bladders was 1.07 +/- 0.12 ml and 0.07 +/- 0.01 ml, respectively. The differences were significant (P < 0.01). The ZPV correlated with bladder weight and thus with degree of hypertrophy. Under conditions when weight cannot be determined, e.g., clinically, ZPV may provide a useful measure of the degree of chronic distension and bladder hypertrophy. The pressure-volume curves of the obstructed bladder CMGs in vitro varied between preparations. However, when pressure-volume was converted to stress-stretch using the law of Laplace, the obstructed bladders were all significantly stiffer than the controls. We confirmed this result by step-stretching relaxed bladder strips. The obstructed bladder strips again demonstrated stiffer stress-stretch curves than the controls.

Animals↗

Two mathematical models explain the variation in cystometrograms of obstructed urinary bladders.

Overdistension of the urinary bladder, secondary to outlet obstruction, causes cellular changes in the bladder wall, including hypertrophy of the smooth muscle cells, which increase bladder mass. To investigate the effects of increased mass on the cystometrogram (CMG), we have developed two mathematical models. In the first model, we assume that mass is added such that the largest bladder volume at zero transmural pressure, the zero pressure volume (ZPV), is constant, It predicts increased pressures and decreased compliance in the CMG. In the second model, we assume that both mass and ZPV increase proportionally. It predicts unchanged pressures, increased compliance, and increased capacity in the CMG. These results allow use to divide animal experiments in the literature into two groups. Cystometrograms performed on animals that have had outlet obstruction induced by a cuff method, inducing a small increase in mass, belong to the first group: hypertrophy with no change in ZPV. Cystometrograms performed on animals that have had outlet obstruction induced by a ligature method, inducing a large increase in mass, belong to the second group: hypertrophy with increased ZPV. We conclude that increased ZPV results from a more severe obstruction which is indicated by the increased capacity and compliance.

Animals↗

Preliminary noninvasive back-pressure recordings of bladder pressure.

Obstructive voiding is best evaluated with urodynamics, including bladder pressure and urine flow rates. Until recently, the recording of bladder pressure required the use of a urethral catheter. In preliminary observations, a noninvasive back-pressure method using an external condom catheter has been introduced to determine bladder pressure. This device uses a side tube for pressure recording and an outlet tube that is clamped for short periods of time. We have investigated design criteria for back-pressure recording techniques. In the laboratory setting using a plastic model, we determined that a low compliance condom is needed. In addition, a back flow of fluid during the clamping procedure helps to obtain quick back pressures and facilitates evaluation of pressure when low flow rates are present. These modified condom devices were evaluated in four male subjects. Back pressures were not statistically different than bladder pressures recorded with a urethral catheter. The use of back pressures in the evaluation for obstructive uropathy can be enhanced by using a pressure and flow nomogram.

Humans↗

The effect of urinary bladder shape on its mechanics during filling.

Despite the normal variation in the shape of the urinary bladder, it has always been modeled as a sphere. We have investigated whether its steady-state pressure-volume relation would be significantly different if it were a spheroid. From pressure-volume curves of anesthetized dogs, we deduced stress-strain constitutive relationships for the bladder wall material. We then solved the equilibrium equations for prolate and oblate spheroids with these constitutive relationships and predicted stress, strain, and volume at 120 different transmural pressures and eight different eccentricities of both types of spheroids. The pressure-volume relation of the prolate spheroid never differed very much from that of a sphere. However, an oblate spheroid made of urinary bladder material is significantly more compliant than either a prolate spheroid or a sphere made of the same material. Applications include identification of the position of highest stress in the bladder wall, estimation of material properties of urinary bladders, and determination of the physiological signal indicating bladder fullness.

Algorithms↗

Does it matter, the shape of the bladder?

To determine if the pressure-volume curve of the urinary bladder is dependent on its shape, we compared the pressure-volume curves of spherical, prolate spheroidal, and oblate spheroidal bladders, all made of the same material. We found that oblate spheroidal bladders are significantly more compliant than either spherical or prolate spheroidal bladders. Since the capacity of normal oblate spheroidal bladders is not larger in vivo than those of any other shape bladder, we have concluded that bladder fullness can not be determined by transmural bladder pressure alone.

Animals↗

Erector spinae activation and movement dynamics about the lumbar spine in lordotic and kyphotic squat-lifting.

Activation of the erector spinae during squat lifts depends on the initial posture of the lumbar spine. The authors assessed erector spinae activation by electromyography during squat lifts from lordotic and kyphotic postures, measured kinematics of the lifts from digitized video images, and inferred torques from the kinematics, using a two-dimensional model of a human lifting in the sagittal plane, with a joint at L3. Lifts from the lordotic initial posture had peak electromyographic signals early in the lift, whereas lifts from kyphotic initial posture had an initial "flexor relaxation," and peak activity in the middle of the lift. Lumbar flexion was much greater in lifts from kyphotic initial position. Torques required about L3 were similar between the two postures, though somewhat larger initially in lifts from kyphosis. The largest torques were therefore sustained by flexed lumbar spines, during periods of little or no erector spinae activity, in lifts made from kyphotic initial position. A sizable portion of the early torque is inertial, and therefore strongly dependent on movement time. Movements with a 30-lb load in the hands were similar, in kinematics and electromyography, to unloaded lifts, though longer in duration. The clinical implications of the differences in activation with posture, the practical implications of the inertial component of torque, and the need for consideration of lumbar posture in future modeling of squat lifting are discussed.

Adult↗