Gallbladder contraction in patients with pigment and cholesterol stones

Thirty gallbladders were studied in vitro; 5 had black pigment stones and 25 contained manifestations of excess cholesterol in bile. Of the 25, 14 had cholesterol stones, 7 had macroscopic cholesterolosis, and 4 had cholesterol crystals. There were no differences in basal active tension among these groups, but the force of spontaneous phasic contractions was reduced in gallbladders with cholesterol stones, cholesterolosis, and cholesterol crystals compared with specimens with pigment stones (p less than 0.001). The forces developed in response to cholecystokinin-8 (10(-10)-10(-6) M), acetylcholine (10(-7)-10(-3) M), and potassium chloride (20-60 mM) were greater in strips from specimens with pigment stones than in strips from specimens with cholesterol stones or cholesterolosis (p less than 0.001). In cholesterol stones and cholesterolosis specimens, relatively strong muscle strips had similar responses to 10(-6) M cholecystokinin-8 in normal calcium (2.5 mM) and in the absence of extracellular calcium. Weaker muscle strips had a reduced response to cholecystokinin-8 in the absence of extracellular calcium (p less than 0.01). It is concluded that muscle strips exposed to bile with excess cholesterol have a reduced contractility compared with muscle strips from specimens with pigment stones; this impaired contractility precedes gallstone formation, and results from muscle dysfunction.     

Developmental characteristics of the kitten antrum

The changes in dietary constituents during growth and development from predominantly liquid to mixed solid liquid meals places an increasing burden on the antrum, which is required to triturate solids. The authors hypothesize that concomitant with these changing dietary constituents different pathways are used to mediate contraction in response to acetylcholine. Smooth muscle cells were isolated by collagenase digestion from the fundus and circular muscle layer of the antrum in the adult cat and 1-week-old kitten. The unstimulated cells from the fundus and antrum were larger in the adult than in the kitten. In normal physiological salt solution, all cells contracted in a similar dose dependent manner in response to acetylcholine in both age groups. Fundic muscle cell contraction in response to acetylcholine was unchanged in calcium-free physiological salt solution or in the presence of the calcium channel blocker, methoxyverapamil. In the adult, antral cells contracted 50% less in the absence of extracellular calcium. In the kitten, antral cells did not contract under the same conditions. After permeabilization with saponin, fundic muscle cells from the adult and kitten contracted fully in response to 1,4,5-inositol trisphosphate, whereas contraction of adult antral cells was reduced by 50% and contraction of kitten antral cells was completely blocked. These data suggest that isolated muscle cells from the fundus of both the adult cat and newborn kitten use intracellular calcium stores to contract in response to acetylcholine and 1,4,5-inositol triphosphate. In adult antral cells, acetylcholine-induced contraction requires both influx of extracellular calcium and release of intracellular calcium. In kitten antral cells, intracellular calcium stores are not used or available to mediate contraction in response to acetylcholine.     

Hydrophilic but not hydrophobic bile acids prevent gallbladder muscle dysfunction in acute cholecystitis

The pathogenesis of acute cholecystitis (AC) is controversial. Bile acids may be involved in the pathogenesis of AC because the hydrophobic chenodeoxycholic acid (CDCA) reproduced in vitro the muscle dysfunction observed in AC and was prevented by the hydrophilic ursodeoxycholic acid (UDCA). The present study examined the in vivo effects of UDCA or CDCA on gallbladder muscle dysfunction caused by AC. Guinea pigs were treated with placebo, UDCA, or CDCA for 2 weeks before sham operation or induction of AC by bile duct ligation (BDL) for 3 days. Pretreatment with oral UDCA prevented the defective contraction in response to agonists (acetylcholine [ACh], cholecystokinin 8 [CCK-8], and KCl) that occurs after BDL. Prostaglandin (PG) E(2)-induced contraction remained normal in the placebo and UDCA-treated groups but was impaired in the CDCA-treated group. Treatment with UDCA also prevented the expected increase in the levels of H(2)O(2), lipid peroxidation, and PGE(2) content in the placebo-treated AC group, whereas CDCA caused further increases in these oxidative stress markers. The binding capacity of PGE(2) to its receptors and the activity of catalase were reduced after treatment with CDCA. Treatment with UDCA enriched gallbladder bile acids with its conjugates and reduced the percentage of CDCA conjugates. In contrast, treatment with CDCA significantly decreased the percentage of UDCA in bile. In conclusion, oral treatment with UDCA prevents gallbladder muscle damage caused by BDL, whereas oral treatment with CDCA worsens the defective muscle contractility and the oxidative stress.     

Pressure tension, and force of closure of the human lower esophageal sphincter and esophagus.

The mechanical characteristics of the circular muscle of the human lower esophageal sphincter and esophagus were studied in subjects with competent and incompetent sphincters. Pressure-diameter curves were constructed by producing various degrees of circumferential stretch with pressure-measuring probes of increasing diameter. The circumferential membrane tension (force of closure) and the circumferential stress (muscle tension) of the circular muscle layer were also calculated from these data. The pressure-diameter curves of competent and incompetent sphincters were different in magnitude and shape. Incompetent sphincters had lower pressures at all diameters, with pressure gradually increasing with larger probe diameter. In contrast for competent sphincters the pressure was highest near closure, with an initial decline and then an increase in pressure with increasing probe diameter. Both shape and magnitude of pressure-diameter curves of competent and incompetent sphincters were interchangeable when manipulated by pharmacologic agents. Urecholine increased the pressures and changed the incompetent pressure-diameter curve to the levels of the competent sphincter; conversely. Pro-Banthine decreased pressures and changed the shape of the competent pressure-diameter curve to the levels of the incompetent sphincter. Force of closure and circular muscle tension curves of competent and incompetent sphincters were similar in shape but were higher at all diameters for competent sphincters. Force of closure and circular muscle tension increased with larger probe diameter. However, the diameter of optimal tension development was larger than the largest probe used and certainly far from closure. Fundoplication increased the magnitude and changed the shape of the incompetent pressure-diameter curve to one similar to a competent curve. This pressure change was associated with an increase in the force of closure, suggesting that fundopliation modified the length-force of closure characteristics of the incompetent spincter.     

Effect of cholecystokinin and the octapeptide of cholecystokinin on the feline sphincter of Oddi and gallbladder. Mechanisms of action.

We studied the effect of cholecystokinin (CCK) and the octapeptide of cholecystokinin (OP-CCK) on the feline gallbladder and sphinecter of Oddi. Both CCK caused a dose-dependent gallbladder contraction and sphincter of Oddi relaxation. The half-maximal responses of the sphincter of Oddi were 6 ng/kg for OP-CCK and 0.15 Ivy-dog U/kg for CCK, which were lower than those of the gallbladder with 28 ng/kg and 0.32 Ivy-dog U/kg, respectively. The effect of OP-CCK on the gallbladder was partially blocked by tetrodotoxin (P < 0.02), hexamethonium alone (P < 0.05), or a combination of hexamethonium and atropine (P < 0.01). The gallbladder response to CCK was not blocked by either atropine alone (P < 0.60) or adrenergic antagonists (P > 0.40). The sphincter of Oddi response to OP-CCK was blocked by tetrodotoxin (P < 0.001) but it was not blocked by cholinergic (P < 0.20) or adrenergic antagonists (P < 0.60). After complete denervation with tetrodotoxin, OP-CCK caused sphincter of Oddi contraction. These findings indicate that there are two excitatory receptors for CCK in the gallbladder, one at the cholinergic neurons and the other at the level of the gallbladder muscle. There are also two receptors for CCK in the sphincter of Oddi, one that is inhibitory, and present at the noncholinergic, nonadrenergic neurons, and the other, excitatory, at the circular muscle.     

Effect of bilateral sacral decentralization on detrusor contractility and passive properties in dog

A series of five dogs underwent complete parasympathetic decentralization through a lumbosacral laminectomy. A full-thickness biopsy was taken from the anterior wall of the bladder before and 12 weeks after surgery. Both mucosa and adventitia were dissected out and muscle layer was cut into several consecutive longitudinal strips. Each strip was mounted in a muscle chamber and frequencyresponse curves were obtained at different pulse duration. Activelpassive force-length relationships were then obtained under condi tions of maximal electrical stimulation (100 V, 2 msec, 40 cps), by stretching the strips in successive increments until length of maximal active force development was reached. Curves were normalized per unit cross-sectional area of muscle. The maximum active stress of the specimens was taken as a measure of bladder contractility, and the rate of exponential increase in passive stress with strain (ratio of deformed to undeformed length) as a measure of detrusor stiffness. Twelve weeks after detrusor decentralization the following changes were found: (1) The frequency that yielded maximum contraction was 10 cps at 2- and 5-;msec pulse duration as compared to 40 cps in controls at every pulse duration. (2) The maximum active stress was 123.9 ± 13.8 vs 244.7 ± 24.7 gm/cm² in controls (p<.001). (3) The level of strain corresponding to the maximal active stress was significantly reduced. (4) The stiffness of the bladder wall was markedly increased; the rate of exponential increase was 4.47 ± 0.63 vs 2.19 ± 0.42 in controls (p<.001). (5) Thickness of the bladder wall was significantly increased (7 ± 1 vs 4 ± 1 mm; p<.001). (6) Histology sections of the specimens demonstrated collagen infiltration in all layers as well as smooth muscle hyperplasia. In summary, the effects of parasympathetic decentralization of the bladder wall are collagen infiltration, increased thickness, increased stiffness, and decreased contractility.     

Force-velocity relationships of guinea pig ureter

Longitudinal force-velocity relationships of the guinea pig ureter were studied in vitro in 3 age groups: 2 to 3 weeks, 2 to 3 months and 2 to 3 years. Velocity of shortening depends on the load lifted and not on the initial length of the muscle. Force-velocity relationships did not change with age, but the isometric force when the velocity is zero and no shortening occurs, increased with age. The shortening of the muscle, expressed as per cent of in vivo length, was independent of age and of preload. Therefore, work performed by a unit length of ureter which is the product of shortening and load lifted, and power which is the product of velocity and load lifted, are unaffected by age or by initial length. Thus there appears to be no significant age-related change in isotonic parameters of contraction such as velocity, shortening, work and power.