RESPONSES OF D E T R U S O R S M O O T H M U S C L E TO S T R E T C H A N D RELAXATION: IN VITRO STUDY ALEX E. FINKBEINER, M.D. PAT D. O ' D O N N E L L , M.D. From the Department of Urology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
vitro model subjecting bladder muscle strips to continuous stretch relaxation rties of passive muscle length and tension. Tension generated as a strip was was found to be stretch-rate dependent. The primary influence of stretch rate by alteration of muscle length; however, stretch and relaxation rates do insmooth muscle properties of hysteresis, stress-relaxation, and adaptation. The curve to the point of bladder contraction seen clinically during cystometry in tact subject can be reproduced in isolated bladder muscle strips. The bladder is a result of passive smooth muscle properties of muscle length and tension , be altered by superimposed neurologic influences.
usly published experiments the effects of the rate of travesical pressure in anescontrolled eystometry and lund a negligible rise in in,ith slow filling rates; how~rated filling rate, a rapid seen. Using this model he guration of the eystometrie on) was altered by the rate Fhis in vivo study demonieal pressure (bladder wall influenced by the filling ). The stretch responses of intact animal may be inetors including the nervous ~dder function. of the rate of stretch on ion independent of the in:animal requires an in vitro que. The objective of this Line the in vitro tension rebladder muscle strips to treteh and relaxation°
1990
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Material and Methods Adult female guinea pigs and rats were sacrificed in a carbon dioxide chamber, and their urinary bladders were immediately removed. The bladders were emptied, and tagging sutures were placed on the adventitial surfaces of the body of the bladder marking resting lengths of strips 17 m m long and 5-7 m m wide. The strips were excised and suspended in a tissue bath containing Locke's//2 solution of pH 7.3, perfused by a gas mixture of 95% oxygen and 5 % carbon dioxide, and kept at a constant 37 °C temperature by a circulation bath. The strip was anchored to the base of the bath by a plastic clip with the other end of the strip suspended by a silk suture to a Grass isometric force transducer which was electrically connected to a Sanborn polygraph. The force transducer was suspended from a Harvard micromanipulator by which changes in length and tension could be made. The mieromanipulator was, in turn, suspended from a mechanical puller by which the strip could be continuously
V O L U M E XXXVI, N U M B E R 2
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10
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100
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120
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1. Relationship of tension versus time of (A) rat bladder muscle strips and (B) guinea pig i muscle strips subjected to continuous stretch at four different stretch rates (mean responses with +_ j
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FIGURE 2. Relationship o] tension versus length of (A) rat bladder muscle strips and (B) guinea pig bladder muscle strips subjected to continuous stretch at ]our different stretch rates. Mean responses with +_ 1 S.D. of length (mm). stretched or relaxed at a constant rate of 0.5, 1.0, 2.0, or 3.0 em per hour. A set-screw on the puller allowed one to stop the stretch at any time or change the stretch rate without altering the length of the strip. A millimeter measuring tape was attached inside the bath adjacent to the strip whereby the actual length of the strip could be measured at any Lime throughout the experiments. Utilizing the mieromanipulator slight tension was applied by lengthening the strip until a small upward deflection was noted on the polygraph recording. The strip was, thus, measured and suspended in such a manner that the initial 194,
length of the strip was 17 mm, termed t tial or resting length. The strip was tk lowed to equilibrate for thirty to forty-fir utes until spontaneous contractility w a s The following studies were then eondt 1. Fifteen each guinea pig and rat were continuously stretched at a rate of 0 hr until 2.0 g tension were reached. point the strip was then continuously rel~ the same rate. At five-minute intervals i continuous stretch and relaxation the let the strip was measured and recorded. Af strip was relaxed to resting length (17 m thirty minutes, the sequence was repea continuous stretch and relaxation rates i 2.0, and 3.0 em/hour. 2. In s e p a r a t e strips seven eonsei stretches were performed on each strii stretch rate of 0.5 em/hour with an inter relaxation and fifteen minutes rest interi tween each stretch. Separate strips were c utively stretched seven times at rates of 1. and 3.0 em/hour in a similar manner. 3. Separate strips were stretched sucee at varying stretch rates without interven:~ laxation in various combinations. After a of continuous stretch at one rate, the i was kept at a constant length by the set! for twenty to thirty seconds while thel rate was changed on the mechanical pull~ set-screw was then disengaged, and thi continuously stretched at the new rate intervening relaxation of the strip. Results The time versus tension relationship! continuous stretch of the bladder strips e of the four stretch rates is seen in Figi (rats) and Figure 1B (guinea pigs). Fo i species it is noted that the timeltension re. ship is dependent on the stretch rate, Thl tionship is consistent among individual St
UROLOGY / AUGUST 1990 / VOLUME XXXVI,
J
12.0 cm/ttr,] A B //
,/
/
10.5 era/Hr.] A B /"
/'
//
/
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3. Diagrammatic representation of tenius time of bladder muscle strips subjected to t continuous stretch at same rate with interrelaxation to baseline length-tension. Re~tretch at same rate results in progressive right of curve (phenomenon of hysteresis). ienomenon is seen if strip is continuously re~ same rate after it was continuously • Phenomenon is seen at each of the four 'ares (A = initial stretch; B = subsequent et same stretch rate).
f3.Oj
12.01
Time
4. Diagrammatic representation of ten~us time of bladder muscle strip subjected to continuous stretch rates (parenthesis = 'ates at cm/hr). During the time stretch rate ied to new rate, muscle strip is held at coningth (isometric). This time depicted by i: Slope of tension~time curves varies with itretch, and stress-relaxation is noted during erval strip is kept isometric.
s the calculated means of all strips. All the relationship of the curves between rates was similar for both rats and ! pigs, the guinea pig strips exhibited a 'sh" fit-to-the-left " at all stretch rates cornwith the rat strips. d a t a were then analyzed by c o m p a r i n g to serially measured length of the strip of the four stretch rates. In both species ;ultant length/tension curves for the four i rates were v i r t u a l l y i d e n t i c a l (Fig. 2). i t h e differences in tension versus ~time ,ith varying stretch rates were length de-
(30~ Time
FICURE 5. Diagrammatic representation of tension versus time of bladder muscle strip subjected to varying initial and subsequent continuous stretch rates (parenthesis = stretch rates at cmdir) with intervening period at which strip is held at constant length (isometric). During isometric period, relaxation of strip occurs (stress-relaxation); rate and duration of relaxation is directly related to preceding stretch rate (compare preceding stretch rates of 0.5 to 3.0 cm/hr). On initiation of new stretch rate relaxation of strip continues. Rate and duration of this relaxation is directly related to preceding stretch rate and inversely related to new stretch rate.
W h e n the strips were continuously stretched at a particular stretch rate, relaxed for fifteen minutes, and stretched again at the same rate, the subsequent time/tension curve shifted to the right (Fig. 3). After a period of relaxation subsequent repeated stretch at the same rate resuited in further shifting of the curve to the right. This continued shift eventually ceased after repeated stretch and relaxation with stabilization and superimposition of the curves after the fourth to sixth stretch. This p h e n o m e n o n was seen at each stretch rate. W h e n the strips were continuously stretched at a particular stretch rate and then continuously relaxed at the same stretch rate, the relaxation curves also "shifted to the right"; this was noted at each of four stretch/relaxation rates. In the strips that were stretched at various successive stretch rates w i t h o u t intervening relaxation several p h e n o m e n a were observed (Figs• 4, 5): 1. D u r i n g the t w e n t y to thirty seconds at w h i c h the strip was kept at a constant length d u r i n g conversion to a n e w stretch rate, a decrease in tension (stress-relaxation) of the strip was observed. T h e rate of r e l a x a t i o n was directly related to the rate of previous stretch;
/ AUGUST 1990 / VOLUME XXXVI, NUMBER 2
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i.e., the rate of relaxation following a period of stretch at 3.0 era/hour was greater t h a n that following a stretch rate of 0.5 em/hour. 2. With resumption of eontinuous stretch at a new stretch rate, the initial portion of the time/tension curves was influeneed by the preeeding stretch rate. W h e n a particular rate of streteh was preeeded by a lower stretch rate, the eurve almost immediately assumed the configuration characteristic of its new stretch rate. However, if the subsequent stretch rate was preceded by a higher stretch rate, the characteristic stress-relaxation configuration continued even while the strip was being stretched at the new stretch rate. Tile duration and extent of the relaxation was inversely proportional to the subsequent stretch rate; i.e., a stretch rate of 2.0 e m / h o u r preceded by a rate of 3.0 era/hour h a d a shorter duration and less total relaxation during the early stage of stretch t h a n did a subsequent stretch rate of 0.5 e m / h o u r which h a d been preceded by a stretch rate of 3.0 era/hour. 3. At the eonelusion of the subsequent stressrelaxation or decay in tension after a period during continuous stretch at a n e w stretch rate, the time/tension curves assumed the configuration unique to the n e w continuous stretch rate regardless of t h e s u b s e q u e n t or p r e c e d i n g stretch rate. Comment The meehanieal properties of the smooth musele both in vivo and in vitro are described in terms of the relationships of foree/veloeity, aetive/length/tension, and passive/length/tension. In this in vitro study of bladder smooth musele, the properties of passive/length/tension was ino vestigated by measuring the ehanges in tension resulting from passive ehanges in length. In work with eats, Tang and tluch 4 demonstrated that the bladder tonus is non-neural in nature and refleets the physieal state of the bladder wall. Studies of dead and alive kittens 5 show that the bladder in both groups exhibit the same general elastie characteristics whieh indieate that both adaptation and tension deeay are due to intrinsie bladder musele properties. In another series of studies involving sympatheetomy, p a r a s y m p a t h e c t o m y , and eomplete denervation, 2'3 it was concluded that the pressure accumulation p h e n o m e n o n is due to bladder wall properties and that the adaptation of the bladder during natural filling is due to inherent properties of the bladder muscle. Similarly, the responses of the isolated muscle strip
196
in our study represents tension wall properties. Although intri sue within the muscle was not the studies, the responses mere sidered passive and not active observed were attributed to p muscle tissue alone since the eh oeeurred in muscle strips in a I from the intact animal and dew lation. Klevmark 1 concluded that tt determines the slope of the pre: the intravesieal pressure patter~ of the actual bladder volume. during eystometry to a given same subject varies with the rat no rise in intravesieal pressur, n o r m a l filling rate. Stepwise during eystometry amplifies th lus eharaeterized by a pressure a pressure fall. With slow eontr increasing pressure from inere~ is gradual and not followed by D u r i n g filling intramural tensi( tinuously as a function of pres: Radius influences tension only gree of filling while pressure du is r a t e - d e p e n d e n t . He eonel streteh stimulus is due to the r~ degree of filling which can f~ preted in terms of the viscous erties of bladder smooth musel Coolsaet 6 noted that the pres der is proportional to the rate infusion rate. This rate depenq p e n d e n t on active musculature the shape of the pressure eurve~ rates of strain (change in lengt feet of rate of filling on the curve is least at the start of stre at the end reflecting partieipat to elongation by nonmuseular Carpenter 7 and Uvelius 8 hav a linear relationship in vivo k v o l u m e , b l a d d e r radius, an length with muscle fibers iner nearly twofold w h e n the blm physiologic eapaeity. W h e n our data are analyzed sion versus time at various stre sultant curves are in agreemen ings of o t h e r s t h a t i n t r a w (tension) is d e p e n d e n t on t (stretch). However, w h e n the analyzed by p l o t t i n g tension
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; s t r e t c h rates, the resultant ly identical and superimposmggest that intravesieal presg eystometry prior to detrusor ependent on bladder muscle ges that are seen in eystometLry to varying filling rates rein muscle length indueed by Lrate. A "shift to the left" of lrve with higher filling rates lment of a particular musele aorter time interval. Regard(within limits), the bladder vesieal pressure) should be esat identical musele lengths. a-tension in vitro studies sugeh responses are eomparable kaet bladder in a healthy orfilling phase of eystometry in muscle responds to increased Le with increased pressure atfive p r o p e r t i e s of b l a d d e r Lthe neurologically intaet orof the passive-length-tension ter muscle appear to be a malder storage disorders which ty clinical bladder dysfunce-length-tension properties of muscle enable the b l a d d e r ;torage to occur normally. : property of smooth muscle is has been noted in vivo and adder. W h e n fluid is instilled vn at the same rate, the pres7e fails to follow identical mon that stabilizes after time periments. 6'v R e m i n g t o n and that subsequent streteh and fred to the right" which they techanical model of dash pots ur experiments the tension/ ength curves were c o m p a r e d e strip subjected to continued rate followed by eontinu:he same fixed rate. A eom',tch curves to the relaxation strip revealed a "shift-to-thep h e n o m e n o n ) of the relaxting less tension at identieal ,'rvals. :es of a bladder musele at a ate following intervening pealso resulted in subsequent of the tension versus time
I' 1990
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Several properties of bladder smooth muscle can be demonstrated by varying the stretch rate of the muscle w i t h o u t intervening relaxation. After a strip is stretched at a particular rate and then kept at a eonstant length (isometric), a subsequent decrease in tension occurs--a phen o m e n o n c o m m o n to smooth muscle k n o w n as stress-relaxation or adaptation. Stretch-relaxation or adaptation can be demonstrated both in muscle strips and clinically and is seen in both living and dead bladders. ~ v D u r i n g eystometry, 2,6 stepwise filling results in an increase in pressure followed by a fall in pressure between filling with the adaptation greater at height volumes. Stepwise filling amplifies the stretch stimulus characterized by a pressure rise followed by a fall in pressure. With slow controlled filling, inereasing pressure from increasing filling rate is gradual and not followered by a pressure fall.: Stepwise e m p t y i n g results in a rapid decrease in pressure followed by a slow rise. At constant strain, pressure decreases in time while after strain, release pressure increases in time. Both are thought to be seeondary to passive processes. Elastie behavior is nonlinear, and the ability to release tension following elongation probably is secondary to viscosity p h e n o m e n o n . 7 It was noted in our muscle strip experiments that the rate of deerease in tension after stretching the strip and then holding it at a constant length (isometric) was directly related to the rates of the preceding stretch. Likewise, with resumption of stretch at a new stretch rate, the initial tension/time response was influeneed by the rate of preeeding stretch. This appears to be a continuation of the streteh-relaxation properties that continues for a time and alters the subsequent streteh response. With continuation of eontinuous stretch the tension/time curve eventually assumes the characteristic tension/time relationship assoeiated with that p a r t i c u l a r stretch rate. Coolsaet 6 noted that given a certain volume in the bladder and kept eonstant, the pressure will increase or decrease d e p e n d i n g on the preceding condition of volume. Klevm a r k 1 noted that the pressure remained at a higher level after subsequent reduction in filling rate (pressure accumulation p h e n o m e n o n ) ; the level depended on h o w quickly the rate was redueed. Conclusion Several responses of bladder smooth muscle subjected to streteh and relaxation can be attributed to the intrinsic physical properties of
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bladder smooth muscle. The slope of a timetension curve of bladder smooth muscle subjetted to continuous stretch or relaxation is dep e n d e n t on its stretch rate. However, w h e n these same data are plotted as tension versus length of muscle the curves become superimposed indicating that tension is directly related to length of stretch regardless of the stretch rate. Muscle strips subjected to repeated stretch at the same stretch rate exhibit a %hilt-to-theright" of the tension versus t i m e or length curves. Likewise, a "shift-to-the-right" of the curves was noted w h e n the strips were continuously relaxed after being eontinuously stretched at the same rate. This relaxation p h e n o m e n o n is an intrinsic eharaeteristie of the smooth musele and not neurologically mediated. Stress-relaxation or adaptation is also an intrinsic property characterized by relaxation or decrease in tension of the muscle strip w h e n held at a constant length (isometric) after a period of stretch. The rate and duration of isometrie stress-relaxation is directly related to the rate of p r e c e d i n g streteh. After subsequent streteh stress-relaxation eontinues, its rate and duration of whieh
198
is inversely proportional to the rate quent stretch. Little Rock, Arka (DR. FIN] References 1. Klevmark B: Motility of the urinary bladder filling at physiologieal rates, t. tntravesieal pres studied by a new method of eystometry, Acta Phy: 565 (1974). 2. Klevmark B: Motility of the urinary bladder filling at physiological rates. II. Effects of extrinsic ration on intramural tension and on intravesieal terns, Acta Physiol Scand 101:176 (1977). 3. Klevmark B: Motility of the urinary bladder filling at physiological rates. III. Spontaneous rhyl contractions in the conscious and anesthetized ani~ of distention and innervation, Stand J Urol Net (1980). 4. Tang P, and Ruch TC: Non-neurogenic ba~ tonus, Am J Physiol 181:249 (1955). 5. Remington JW, and Alexander RS: Stretch b, bladder as an approach to vascular distensibility, 181:240 (1955). 6. Coolsaet BLRA: Stepwise cystometry. A new vestigate properties of the urinary bladder (Thesis), versify, Rotterdam, The Netherlands (1977). 7. Carpenter FG: Motor responses of bladder sin( relation to elasticity and fiber length, invest Urol { 8. Uvelius B: Isometric and isotonic length-ten and variations in cell length in longitudinal smoott rat urinary bladder, Acta Physiol Scand 97" 1 (197,
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AUGUST 1990
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VOLUME XXXVI,
vitro model subjecting bladder muscle strips to continuous stretch relaxation rties of passive muscle length and tension. Tension generated as a strip was was found to be stretch-rate dependent. The primary influence of stretch rate by alteration of muscle length; however, stretch and relaxation rates do insmooth muscle properties of hysteresis, stress-relaxation, and adaptation. The curve to the point of bladder contraction seen clinically during cystometry in tact subject can be reproduced in isolated bladder muscle strips. The bladder is a result of passive smooth muscle properties of muscle length and tension , be altered by superimposed neurologic influences.
usly published experiments the effects of the rate of travesical pressure in anescontrolled eystometry and lund a negligible rise in in,ith slow filling rates; how~rated filling rate, a rapid seen. Using this model he guration of the eystometrie on) was altered by the rate Fhis in vivo study demonieal pressure (bladder wall influenced by the filling ). The stretch responses of intact animal may be inetors including the nervous ~dder function. of the rate of stretch on ion independent of the in:animal requires an in vitro que. The objective of this Line the in vitro tension rebladder muscle strips to treteh and relaxation°
1990
/
Material and Methods Adult female guinea pigs and rats were sacrificed in a carbon dioxide chamber, and their urinary bladders were immediately removed. The bladders were emptied, and tagging sutures were placed on the adventitial surfaces of the body of the bladder marking resting lengths of strips 17 m m long and 5-7 m m wide. The strips were excised and suspended in a tissue bath containing Locke's//2 solution of pH 7.3, perfused by a gas mixture of 95% oxygen and 5 % carbon dioxide, and kept at a constant 37 °C temperature by a circulation bath. The strip was anchored to the base of the bath by a plastic clip with the other end of the strip suspended by a silk suture to a Grass isometric force transducer which was electrically connected to a Sanborn polygraph. The force transducer was suspended from a Harvard micromanipulator by which changes in length and tension could be made. The mieromanipulator was, in turn, suspended from a mechanical puller by which the strip could be continuously
V O L U M E XXXVI, N U M B E R 2
193
3.0 cmlHr. 3,0 crn/Hr.
Z,O cm/Hr
10 cm/ltr,
Z/
tl.5 cm/ttr
2.0 cmllir.
1.fl cmlHr.
2.11-
o -
I
0.5
A
10
20
30
40
50
60
70
80
9h
100
110
Time - - Minutes
120
130
20
BO
40 Time
-
-
.
Minutes
1. Relationship of tension versus time of (A) rat bladder muscle strips and (B) guinea pig i muscle strips subjected to continuous stretch at four different stretch rates (mean responses with +_ j
FZCURE
a--.-,~ ~ ~ , o- o
0.5 cm/Hr I.O crq/Hr 2.0 cm/er 3.0 ¢m/er
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I±v.II ~/c-
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i8
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20
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24
25
2'6
27
[±1.51 2.0-
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1+1.41 ;.~z f l ~ ~ /
1 + 1 , 2 1 . ~ S c~S~ cb
(+-! .-~-'"
m
It.0 == =~ 0.5-
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at7
18
19
20
21 22 Length - - Millimeters
23
24
25
FIGURE 2. Relationship o] tension versus length of (A) rat bladder muscle strips and (B) guinea pig bladder muscle strips subjected to continuous stretch at ]our different stretch rates. Mean responses with +_ 1 S.D. of length (mm). stretched or relaxed at a constant rate of 0.5, 1.0, 2.0, or 3.0 em per hour. A set-screw on the puller allowed one to stop the stretch at any time or change the stretch rate without altering the length of the strip. A millimeter measuring tape was attached inside the bath adjacent to the strip whereby the actual length of the strip could be measured at any Lime throughout the experiments. Utilizing the mieromanipulator slight tension was applied by lengthening the strip until a small upward deflection was noted on the polygraph recording. The strip was, thus, measured and suspended in such a manner that the initial 194,
length of the strip was 17 mm, termed t tial or resting length. The strip was tk lowed to equilibrate for thirty to forty-fir utes until spontaneous contractility w a s The following studies were then eondt 1. Fifteen each guinea pig and rat were continuously stretched at a rate of 0 hr until 2.0 g tension were reached. point the strip was then continuously rel~ the same rate. At five-minute intervals i continuous stretch and relaxation the let the strip was measured and recorded. Af strip was relaxed to resting length (17 m thirty minutes, the sequence was repea continuous stretch and relaxation rates i 2.0, and 3.0 em/hour. 2. In s e p a r a t e strips seven eonsei stretches were performed on each strii stretch rate of 0.5 em/hour with an inter relaxation and fifteen minutes rest interi tween each stretch. Separate strips were c utively stretched seven times at rates of 1. and 3.0 em/hour in a similar manner. 3. Separate strips were stretched sucee at varying stretch rates without interven:~ laxation in various combinations. After a of continuous stretch at one rate, the i was kept at a constant length by the set! for twenty to thirty seconds while thel rate was changed on the mechanical pull~ set-screw was then disengaged, and thi continuously stretched at the new rate intervening relaxation of the strip. Results The time versus tension relationship! continuous stretch of the bladder strips e of the four stretch rates is seen in Figi (rats) and Figure 1B (guinea pigs). Fo i species it is noted that the timeltension re. ship is dependent on the stretch rate, Thl tionship is consistent among individual St
UROLOGY / AUGUST 1990 / VOLUME XXXVI,
J
12.0 cm/ttr,] A B //
,/
/
10.5 era/Hr.] A B /"
/'
//
/
13.01/
/z //
/Z
[2.01///
-
Time or Length
3. Diagrammatic representation of tenius time of bladder muscle strips subjected to t continuous stretch at same rate with interrelaxation to baseline length-tension. Re~tretch at same rate results in progressive right of curve (phenomenon of hysteresis). ienomenon is seen if strip is continuously re~ same rate after it was continuously • Phenomenon is seen at each of the four 'ares (A = initial stretch; B = subsequent et same stretch rate).
f3.Oj
12.01
Time
4. Diagrammatic representation of ten~us time of bladder muscle strip subjected to continuous stretch rates (parenthesis = 'ates at cm/hr). During the time stretch rate ied to new rate, muscle strip is held at coningth (isometric). This time depicted by i: Slope of tension~time curves varies with itretch, and stress-relaxation is noted during erval strip is kept isometric.
s the calculated means of all strips. All the relationship of the curves between rates was similar for both rats and ! pigs, the guinea pig strips exhibited a 'sh" fit-to-the-left " at all stretch rates cornwith the rat strips. d a t a were then analyzed by c o m p a r i n g to serially measured length of the strip of the four stretch rates. In both species ;ultant length/tension curves for the four i rates were v i r t u a l l y i d e n t i c a l (Fig. 2). i t h e differences in tension versus ~time ,ith varying stretch rates were length de-
(30~ Time
FICURE 5. Diagrammatic representation of tension versus time of bladder muscle strip subjected to varying initial and subsequent continuous stretch rates (parenthesis = stretch rates at cmdir) with intervening period at which strip is held at constant length (isometric). During isometric period, relaxation of strip occurs (stress-relaxation); rate and duration of relaxation is directly related to preceding stretch rate (compare preceding stretch rates of 0.5 to 3.0 cm/hr). On initiation of new stretch rate relaxation of strip continues. Rate and duration of this relaxation is directly related to preceding stretch rate and inversely related to new stretch rate.
W h e n the strips were continuously stretched at a particular stretch rate, relaxed for fifteen minutes, and stretched again at the same rate, the subsequent time/tension curve shifted to the right (Fig. 3). After a period of relaxation subsequent repeated stretch at the same rate resuited in further shifting of the curve to the right. This continued shift eventually ceased after repeated stretch and relaxation with stabilization and superimposition of the curves after the fourth to sixth stretch. This p h e n o m e n o n was seen at each stretch rate. W h e n the strips were continuously stretched at a particular stretch rate and then continuously relaxed at the same stretch rate, the relaxation curves also "shifted to the right"; this was noted at each of four stretch/relaxation rates. In the strips that were stretched at various successive stretch rates w i t h o u t intervening relaxation several p h e n o m e n a were observed (Figs• 4, 5): 1. D u r i n g the t w e n t y to thirty seconds at w h i c h the strip was kept at a constant length d u r i n g conversion to a n e w stretch rate, a decrease in tension (stress-relaxation) of the strip was observed. T h e rate of r e l a x a t i o n was directly related to the rate of previous stretch;
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i.e., the rate of relaxation following a period of stretch at 3.0 era/hour was greater t h a n that following a stretch rate of 0.5 em/hour. 2. With resumption of eontinuous stretch at a new stretch rate, the initial portion of the time/tension curves was influeneed by the preeeding stretch rate. W h e n a particular rate of streteh was preeeded by a lower stretch rate, the eurve almost immediately assumed the configuration characteristic of its new stretch rate. However, if the subsequent stretch rate was preceded by a higher stretch rate, the characteristic stress-relaxation configuration continued even while the strip was being stretched at the new stretch rate. Tile duration and extent of the relaxation was inversely proportional to the subsequent stretch rate; i.e., a stretch rate of 2.0 e m / h o u r preceded by a rate of 3.0 era/hour h a d a shorter duration and less total relaxation during the early stage of stretch t h a n did a subsequent stretch rate of 0.5 e m / h o u r which h a d been preceded by a stretch rate of 3.0 era/hour. 3. At the eonelusion of the subsequent stressrelaxation or decay in tension after a period during continuous stretch at a n e w stretch rate, the time/tension curves assumed the configuration unique to the n e w continuous stretch rate regardless of t h e s u b s e q u e n t or p r e c e d i n g stretch rate. Comment The meehanieal properties of the smooth musele both in vivo and in vitro are described in terms of the relationships of foree/veloeity, aetive/length/tension, and passive/length/tension. In this in vitro study of bladder smooth musele, the properties of passive/length/tension was ino vestigated by measuring the ehanges in tension resulting from passive ehanges in length. In work with eats, Tang and tluch 4 demonstrated that the bladder tonus is non-neural in nature and refleets the physieal state of the bladder wall. Studies of dead and alive kittens 5 show that the bladder in both groups exhibit the same general elastie characteristics whieh indieate that both adaptation and tension deeay are due to intrinsie bladder musele properties. In another series of studies involving sympatheetomy, p a r a s y m p a t h e c t o m y , and eomplete denervation, 2'3 it was concluded that the pressure accumulation p h e n o m e n o n is due to bladder wall properties and that the adaptation of the bladder during natural filling is due to inherent properties of the bladder muscle. Similarly, the responses of the isolated muscle strip
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in our study represents tension wall properties. Although intri sue within the muscle was not the studies, the responses mere sidered passive and not active observed were attributed to p muscle tissue alone since the eh oeeurred in muscle strips in a I from the intact animal and dew lation. Klevmark 1 concluded that tt determines the slope of the pre: the intravesieal pressure patter~ of the actual bladder volume. during eystometry to a given same subject varies with the rat no rise in intravesieal pressur, n o r m a l filling rate. Stepwise during eystometry amplifies th lus eharaeterized by a pressure a pressure fall. With slow eontr increasing pressure from inere~ is gradual and not followed by D u r i n g filling intramural tensi( tinuously as a function of pres: Radius influences tension only gree of filling while pressure du is r a t e - d e p e n d e n t . He eonel streteh stimulus is due to the r~ degree of filling which can f~ preted in terms of the viscous erties of bladder smooth musel Coolsaet 6 noted that the pres der is proportional to the rate infusion rate. This rate depenq p e n d e n t on active musculature the shape of the pressure eurve~ rates of strain (change in lengt feet of rate of filling on the curve is least at the start of stre at the end reflecting partieipat to elongation by nonmuseular Carpenter 7 and Uvelius 8 hav a linear relationship in vivo k v o l u m e , b l a d d e r radius, an length with muscle fibers iner nearly twofold w h e n the blm physiologic eapaeity. W h e n our data are analyzed sion versus time at various stre sultant curves are in agreemen ings of o t h e r s t h a t i n t r a w (tension) is d e p e n d e n t on t (stretch). However, w h e n the analyzed by p l o t t i n g tension
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; s t r e t c h rates, the resultant ly identical and superimposmggest that intravesieal presg eystometry prior to detrusor ependent on bladder muscle ges that are seen in eystometLry to varying filling rates rein muscle length indueed by Lrate. A "shift to the left" of lrve with higher filling rates lment of a particular musele aorter time interval. Regard(within limits), the bladder vesieal pressure) should be esat identical musele lengths. a-tension in vitro studies sugeh responses are eomparable kaet bladder in a healthy orfilling phase of eystometry in muscle responds to increased Le with increased pressure atfive p r o p e r t i e s of b l a d d e r Lthe neurologically intaet orof the passive-length-tension ter muscle appear to be a malder storage disorders which ty clinical bladder dysfunce-length-tension properties of muscle enable the b l a d d e r ;torage to occur normally. : property of smooth muscle is has been noted in vivo and adder. W h e n fluid is instilled vn at the same rate, the pres7e fails to follow identical mon that stabilizes after time periments. 6'v R e m i n g t o n and that subsequent streteh and fred to the right" which they techanical model of dash pots ur experiments the tension/ ength curves were c o m p a r e d e strip subjected to continued rate followed by eontinu:he same fixed rate. A eom',tch curves to the relaxation strip revealed a "shift-to-thep h e n o m e n o n ) of the relaxting less tension at identieal ,'rvals. :es of a bladder musele at a ate following intervening pealso resulted in subsequent of the tension versus time
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Several properties of bladder smooth muscle can be demonstrated by varying the stretch rate of the muscle w i t h o u t intervening relaxation. After a strip is stretched at a particular rate and then kept at a eonstant length (isometric), a subsequent decrease in tension occurs--a phen o m e n o n c o m m o n to smooth muscle k n o w n as stress-relaxation or adaptation. Stretch-relaxation or adaptation can be demonstrated both in muscle strips and clinically and is seen in both living and dead bladders. ~ v D u r i n g eystometry, 2,6 stepwise filling results in an increase in pressure followed by a fall in pressure between filling with the adaptation greater at height volumes. Stepwise filling amplifies the stretch stimulus characterized by a pressure rise followed by a fall in pressure. With slow controlled filling, inereasing pressure from increasing filling rate is gradual and not followered by a pressure fall.: Stepwise e m p t y i n g results in a rapid decrease in pressure followed by a slow rise. At constant strain, pressure decreases in time while after strain, release pressure increases in time. Both are thought to be seeondary to passive processes. Elastie behavior is nonlinear, and the ability to release tension following elongation probably is secondary to viscosity p h e n o m e n o n . 7 It was noted in our muscle strip experiments that the rate of deerease in tension after stretching the strip and then holding it at a constant length (isometric) was directly related to the rates of the preceding stretch. Likewise, with resumption of stretch at a new stretch rate, the initial tension/time response was influeneed by the rate of preeeding stretch. This appears to be a continuation of the streteh-relaxation properties that continues for a time and alters the subsequent streteh response. With continuation of eontinuous stretch the tension/time curve eventually assumes the characteristic tension/time relationship assoeiated with that p a r t i c u l a r stretch rate. Coolsaet 6 noted that given a certain volume in the bladder and kept eonstant, the pressure will increase or decrease d e p e n d i n g on the preceding condition of volume. Klevm a r k 1 noted that the pressure remained at a higher level after subsequent reduction in filling rate (pressure accumulation p h e n o m e n o n ) ; the level depended on h o w quickly the rate was redueed. Conclusion Several responses of bladder smooth muscle subjected to streteh and relaxation can be attributed to the intrinsic physical properties of
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bladder smooth muscle. The slope of a timetension curve of bladder smooth muscle subjetted to continuous stretch or relaxation is dep e n d e n t on its stretch rate. However, w h e n these same data are plotted as tension versus length of muscle the curves become superimposed indicating that tension is directly related to length of stretch regardless of the stretch rate. Muscle strips subjected to repeated stretch at the same stretch rate exhibit a %hilt-to-theright" of the tension versus t i m e or length curves. Likewise, a "shift-to-the-right" of the curves was noted w h e n the strips were continuously relaxed after being eontinuously stretched at the same rate. This relaxation p h e n o m e n o n is an intrinsic eharaeteristie of the smooth musele and not neurologically mediated. Stress-relaxation or adaptation is also an intrinsic property characterized by relaxation or decrease in tension of the muscle strip w h e n held at a constant length (isometric) after a period of stretch. The rate and duration of isometrie stress-relaxation is directly related to the rate of p r e c e d i n g streteh. After subsequent streteh stress-relaxation eontinues, its rate and duration of whieh
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is inversely proportional to the rate quent stretch. Little Rock, Arka (DR. FIN] References 1. Klevmark B: Motility of the urinary bladder filling at physiologieal rates, t. tntravesieal pres studied by a new method of eystometry, Acta Phy: 565 (1974). 2. Klevmark B: Motility of the urinary bladder filling at physiological rates. II. Effects of extrinsic ration on intramural tension and on intravesieal terns, Acta Physiol Scand 101:176 (1977). 3. Klevmark B: Motility of the urinary bladder filling at physiological rates. III. Spontaneous rhyl contractions in the conscious and anesthetized ani~ of distention and innervation, Stand J Urol Net (1980). 4. Tang P, and Ruch TC: Non-neurogenic ba~ tonus, Am J Physiol 181:249 (1955). 5. Remington JW, and Alexander RS: Stretch b, bladder as an approach to vascular distensibility, 181:240 (1955). 6. Coolsaet BLRA: Stepwise cystometry. A new vestigate properties of the urinary bladder (Thesis), versify, Rotterdam, The Netherlands (1977). 7. Carpenter FG: Motor responses of bladder sin( relation to elasticity and fiber length, invest Urol { 8. Uvelius B: Isometric and isotonic length-ten and variations in cell length in longitudinal smoott rat urinary bladder, Acta Physiol Scand 97" 1 (197,
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