John S. Martin

Acute experimental colitis decreases colonic circular smooth muscle contractility in rats

Distal colitis decreases the contractility of the underlying circular smooth muscle. We examined how time after injury and lesion severity contribute to the decreased contractility and how colitis alters the calcium-handling properties of the affected muscle. Distal colitis was induced in rats by intrarectal administration of 4% acetic acid. Contractile responses to acetylcholine, increased extracellular potassium, and the G protein activator NaF were determined for circular muscle strips from sham control and colitic rats at days 1, 2, 3, 7, and 14 postenemas. Acetylcholine stimulation of tissues from day 3colitic rats was performed in a zero calcium buffer, in the presence of nifedipine, and after depletion of intracellular stores of calcium. The colitis was graded macroscopically as mild, moderate, or severe. Regardless of agonist, maximal decrease in force developed 2 to 3 days posttreatment, followed by a gradual return to control by day 14. The inhibitory effect of colitis on contractility increased with increasing severity of inflammation. Limiting extracellular calcium influx had a greater inhibitory effect on tissues from colitic rats; intracellular calcium depletion had a greater inhibitory effect on tissues from control animals. The data suggest that both lesion severity and time after injury affect the contractile response of circular smooth muscle from the inflamed distal colon. Impaired utilization of intracellular calcium may contribute to the decreased contractility.Distal colitis decreases the contractility of the underlying circular smooth muscle. We examined how time after injury and lesion severity contribute to the decreased contractility and how colitis alters the calcium-handling properties of the affected muscle. Distal colitis was induced in rats by intrarectal administration of 4% acetic acid. Contractile responses to acetylcholine, increased extracellular potassium, and the G protein activator NaF were determined for circular muscle strips from sham control and colitic rats at days 1, 2, 3, 7, and 14 postenemas. Acetylcholine stimulation of tissues from day 3 colitic rats was performed in a zero calcium buffer, in the presence of nifedipine, and after depletion of intracellular stores of calcium. The colitis was graded macroscopically as mild, moderate, or severe. Regardless of agonist, maximal decrease in force developed 2 to 3 days posttreatment, followed by a gradual return to control by day 14. The inhibitory effect of colitis on contractility increased with increasing severity of inflammation. Limiting extracellular calcium influx had a greater inhibitory effect on tissues from colitic rats; intracellular calcium depletion had a greater inhibitory effect on tissues from control animals. The data suggest that both lesion severity and time after injury affect the contractile response of circular smooth muscle from the inflamed distal colon. Impaired utilization of intracellular calcium may contribute to the decreased contractility.

An evaluation of neural influences on the sphincter of Oddi in the dog

Opening pressures of the choledochoduodenal junction were measured in anesthetized dogs before and after vagotomy. Measurements were also made in anesthetized, vagotomized dogs prior to and during appropriate electrical stimulation of the severed ends of the peripheral and central vagi and of the peripheral splanchnic nerves. Vagotomy itself was not associated with significant changes in mean ductal opening pressures. Central and peripheral vagal stimulation and peripheral splanchnic nerve stimulation did not yield significant effects on the mean opening pressure parameter. However, changes in circulating fluid volume were shown to significantly influence mean ductal opening pressures. Reductions in systemic arterial pressure were associated with a reduction in mean opening pressures, whereas increases in cardiovascular fluid volume were associated with a marked elevation of opening pressures. It is concluded that ductal opening pressures can be significantly changed by hydraulic factors but are apparently unresponsive to direct neural influences.

Electric Field Stimulation-Induced Guinea Pig Gallbladder Contractions (Role of Calcium Channels in Acetylcholine Release)

Gallbladder motility is modulated by intrinsiccholinergic neurons. The aims of this study were todetermine: (1) the effect of electric field stimulation(EFS) on guinea pig gallbladder smooth muscle, and (2) the role of calcium channels inmediating neurotransmitter release. Gallbladder musclestrips were studied isometrically in vitro. EFS (1-16Hz, 100 V, 0.5-msec pulse width, 30-sec train duration) was used to activate the intrinsic nerves.Exogenous acetylcholine was also used to directlystimulate the smooth muscle. EFS produced afrequency-dependent contractile response that wascompletely abolished by tetrodotoxin. EFS-induced contractions at 16Hz were suppressed by 84 ± 4% with atropine,whereas hexamethonium had no effect. The L-type calciumchannel blocker, nifedipine, reduced EFS contractions by 51 ± 4%, whereas it reduced contractionsto acetylcholine by only 11 ± 5%. The N-typecalcium channel blocker, omega-conotoxin GVIA, reducedEFS-induced contractions by 22 ± 9%, but did notaffect acetylcholine-induced contractions. EFS-induced contractions of theguinea pig gallbladder are primarily mediated byactivation of postganglionic cholinergic neurons. Theacetylcholine release from these cholinergic neurons is regulated by L- and N-type calcium channels.The inhibitory effect of calcium channel blockers on thegallbladder seen in vivo may be in part related toinhibition of acetylcholine release from the intrinsic cholinergic nerves of thegallbladder.

Particulate inhalation during the removal of amalgam restorations

An aerosol that contains amalgam particles is created when a high-speed hand-piece is used to remove an existing amalgam restoration. Those particles smaller than 10 microns are considered to be fully respirable. This means that a significant percentage of the particles have the potential to travel to the terminal alveoli, where they may become lodged. Long-term exposure to fully respirable particles may compromise a persons respiratory function. Amalgam restorations were placed in the typodont teeth of a mannequin designed to simulate the head and the respiratory tract of a patient. The amalgam restorations were removed under three experimental conditions: dry cut (control), wet cut (water spray) with high-velocity evacuation, and wet cut with high-velocity evacuation and a rubber dam. Particulate exposure was evaluated in the simulated respiratory tracts of the patient and the dentist that were equipped with ambient particle sizing samplers. Use of water spray and high-velocity evacuation significantly reduced patient exposure to particles. The use of a rubber dam, together with water spray and high-velocity evacuation, was responsible for a further significant reduction of exposure to particles when compared with water spray and high-velocity evacuation alone. The dentist, however, was exposed to moderate levels of fully respirable particles for all conditions tested. It is therefore recommended that all dental personnel wear face masks while removing existing amalgam restorations.

The mucosal lining of the intramural common bile duct as a determinant of ductal opening pressure.

Microanatomical evidence is presented which shows that the lumen of the intraduodenal portion of the common bile duct is almost completely filled by folds of a highly vascularized mucosa in the dog, cat, rabbit, and human. These folds are most apparent near the intraduodenal ductal orifice, where they almost completely occlude the lumen. Physiological data are presented which indicate that changes in systemic arterial blood pressure are associated with changes in the opening pressures of the choledochoduodenal junction of the cat and dog, which vary in the same direction. Experimental results indicate that bile duct opening pressures of these two species are increased by the intraductal administration of histamine and reduced by the intraductal administration of norepinephrine. A histological examination of the intraductal mucosal folds in this area, subsequent to the administration of the elevating agent, revealed a marked presence of vascular engorgement. It is concluded that the most significant determinant of changes in ductal opening pressures in the cat and dog is probably the state of the mucosal vasculature of the terminal portion of the common bile duct.

Response of Colonic Smooth Muscle from Newborn and Adult Rabbits to Electrical Field Stimulation

ABSTRACT: Electrical Held stimulation (EFS) of circular smooth muscle from the proximal and distal colon of adult rabbits elicits region-specific patterns of contraction and relaxation referred to as on and off responses. The present study examined EFS-mediated on and off responses in neonatal (3− to 5-d-old), juvenile (2-wk-old), and adult rabbits to determine whether colonie motility undergoes a period of postnatal maturation with respect to the pattern of contraction/relaxation that develops in response to stimulation of the enteric nervous system. Muscle strips from the proximal and distal colon were oriented parallel to the circular muscle layer and stimulated electrically (80 V; 0.5-ms pulse width) for 10 s using platinum wire electrodes. Stimulus frequency varied between 1 and 64 Hz. EFS stimulation of circular smooth muscle from the proximal colon of neonatal, juvenile, and adult rabbits was characterized by the development of atropine-sensitive on-con-tractions. The frequency-response curves were similar for each age group. In the distal colon, EFS of circular smooth muscle from neonatal, juvenile, and adult rabbits produced on-relaxations and atropine-insensitive off-contractions. The frequency-response data for the off-contractions were similar for each age group. Although no age-related differences were observed with respect to the pattern of contractile response to EFS, the force of the proximal colon on contractions and the distal colon off-contractions increased as the animals matured. The results suggest that the pattern of colonie enteric neurotransmission is established early in the neonatal period and does not undergo any significant change during the postnatal period. Differences in the force of contraction may reflect differences in the contractility of colonie smooth muscle from neonatal, juvenile, and adult rabbits.

COMPARISON OF THE INHIBITORY EFFECTS OF SPERMINE, PAPAVERINE AND ADRENALINE UPON ISOLATED SEGMENTS OF THE RAT SMALL INTESTINE

1. In the rat isolated duodenal and ileal segments the active baseline force and spontaneous contractile frequency were inhibited by spermine; the relative potencies, estimated as an ED50, were adrenaline papaverine spermine. The changes in baseline force, but not frequency, due to spermine were sensitive to increased calcium.

The differential action of somatostatin on the motor effector system of the canine gastrointestinal tract

Abstract Considerable attention has recently been devoted to the effects of somatostatin on the secretory activities of the digestive system. The opposite is true for the effects of somatostatin on the motor activities of the digestive tract. One of the papers that forms the basis for linking somatostatin with possible digestive system muscle function is the work of Creutzfeldt et al. 1 In this study, somatostatin inhibited gallbladder contraction stimulated by an infusion of exogenous cholecystokinin-pancreozymin in man. In animal experimentation, the somatostatin effect on gallbladder contraction was confirmed in the pig 2 and in the dog. 3 Only a few published abstracts have alluded to the possibility that this substance might influence the motor activities of the gastrointestinal tract. 4–6 In preliminary experiments, spontaneous gastric antral contractions were not modified by somatostatin. 4 On the other hand, somatostatin had a distinct motor effect on the duodenum of the nembutalized dog. 4 Unfortunately, no explanation for this difference in responsiveness was advanced. Therefore, the purposes of these studies were to determine the natures and the mechanisms of action of the effects of somatostatin on the canine stomach, intestines, and extrahepatic biliary system.

Vascular influences on the dynamic stability of the choledochoduodenal junction

Alterations of arterial, hepatic portal, and central venous pressures are shown to be associated with changes in the same direction of the opening pressures of the canine choledochoduodenal junction. Increases in opening pressures subsequent to increases in vascular pressures could be abolished by the intraductal administration of norepinephrine. Experiments employing the systematic intraductal administration of various pharmacological agents produced data that are interpreted to indicate that alterations in ductal opening pressures are preponderantly dependent in the dog upon local vascular effects.

A functional description of the canine choledochoduodenal flutter valve

Forward- and reverse-opening pressures of the choledochoduodenal junction were measured in anesthetized, vagotomized dogs. Mean reverse-opening pressures were found to be significantly greater in most cases including those following the intraductal administration of vasoactive agents which are known to significantly influence mean forward-opening pressures. The polypeptides CCK-PZ and CCK-C8 were ineffective in reducing mean forward-opening pressures regardless of the route of administration. Previously published observations have indicated that mean forward-opening pressures are also unaffected by nervous activity. It is concluded that the canine choledochoduodenal junction possesses the physical and functional properties of a passive flutter valve during duodenal relaxation.