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Biomedical subjects

S K Sarna

Publications and source records attributed to S K Sarna.

At least 19 recordsLinked to original sources

Fractionated doses of ionizing radiation alter postprandial small intestinal motor activity.

We investigated the effects of total abdominal fractionated irradiation on postprandial small intestinal motor activity in five dogs. Five strain-gauge transducers were attached to the seromuscular layer of the duodenum, jejunum, and ileum of each dog to record circular muscle contractions. Radiation (250 cGy) was administered three times a week on alternate days for three successive weeks (total dose, 2250 cGy). Postprandial 4-hr recordings were made once each week during radiation and at one and three weeks following completion of radiation. Duodenal mean amplitude and area under contractions did not change during or following the radiation schedule, but the mean frequency and duration of duodenal contractions decreased during the radiation schedule. Both parameters returned to baseline values postirradiation. Jejunal mean duration, amplitude, area, and frequency of contractions decreased during radiation; mean amplitude and area returned to baseline values postirradiation but not the duration and frequency of contractions. All parameters of ileal contractions decreased during radiation, and all but area and amplitudes remained depressed postirradiation. Significantly decreased strength and frequency of contractions, particularly in the jejunum and ileum occur during and following irradiation. These changes may potentially alter transit time.

Animals

Enterohepatic circulation is essential for regular cycling of duodenal migrating motor complexes in dogs.

The role of enterohepatic circulation and specific bile acids in the initiation and caudad migration of duodenal migrating motor complexes (MMCs) was investigated in conscious dogs. All dogs had spontaneous duodenal MMCs that migrated to the terminal ileum when bile flow was intact. During the first 3 days after total external biliary diversion, no MMCs originated in the duodenum. Instead, all MMCs originated in the jejunum and migrated to the ileum. During the next 4 days of total external biliary diversion, 81% of the MMCs originated in the jejunum and 19% in the duodenum. When normal bile flow was restored after 9 days of total external biliary diversion, regular duodenal MMCs resumed after a delay of 126 +/- 27 minutes. Perfusion of individual bile acids or dogs' own bile, but not saline or alkaline solution, into the duodenum or perfusion of dogs' own bile directly into the ileum during total external biliary diversion restarted duodenal MMCs with a time lag of about 2 hours. The authors conclude that intact enterohepatic circulation is essential for the initiation of regular duodenal MMCs.

Animals

Antral control of gallbladder cyclic motor activity in the fasting state.

The hypothesis that gastric antrum controls the phasic contractions of gallbladder cyclic motor activity in the fasting state was tested. Gallbladder, gastric, and small bowel motor and myoelectric activity was recorded by strain gauge transducers and bipolar electrodes. Gallbladder pressure was measured manometrically by a surgically implanted intraluminal catheter. After control recordings for 4 to 6 weeks, antrectomy and gastroduodenostomy were performed. Six weeks later, bilateral truncal vagotomy was performed in each dog. Recordings were made after each surgical procedure. In the control state, the gallbladder exhibited cyclic motor activity consisting of phasic contractions at a frequency of 0.75 +/- 0.02/min superimposed on an increase in baseline pressure. Antrectomy and gastroduodenostomy completely abolished the phasic contractions of gallbladder cyclic motor activity and significantly decreased the incidence of the cyclic increase in baseline pressure. Subsequent vagotomy had no additional effect on gallbladder cyclic motor activity. In intact dogs, the gallbladder filled from 0% to 80% and emptied from 80% to 100% of the duodenal migrating motor complex cycle, which was considered to begin at the start of phase I activity. Antrectomy significantly altered this pattern; after antrectomy, the gallbladder filled from 0% to 10% and from 90% to 100% and emptied during the remainder of the duodenal migrating motor complex cycle. Subsequent vagotomy had no additional effect on periodic gallbladder filling and emptying. It is concluded that major changes occur in gallbladder cyclic motor activity and its periodic filling and emptying pattern in the fasting state after antrectomy and vagotomy. It is hypothesized that in the absence of cyclic phasic contractions after antrectomy, periodic stirring and agitation of gallbladder bile and its mixing with fresh hepatic bile may not occur in the fasting state. The absence of this phenomenon may lead to supersaturation of bile near the mucosal surface and increase the propensity for precipitation of salts and formation of gallstones.

Animals

Effect of fluid perfusion and cleansing on canine colonic motor activity.

We investigated the effect of absorbable and nonabsorbable fluid perfusion and cleansing on colonic motor activity in eight intact conscious dogs. Each dog was instrumented with an indwelling catheter in the proximal colon and seven strain gauge transducers on the entire colon. After an overnight fast, a control recording was made for 3 h, followed by 3 h of perfusion and 3 additional h of postperfusion recording. Next day, a 3-h recording was made when the colon was empty. The colon exhibited normal migrating and nonmigrating motor complexes in the control uncleansed state. The perfusion of absorbable electrolyte or nonabsorbable Colyte solution immediately disrupted the migrating motor complexes and replaced them with almost continuous but irregular contractions at all recording sites. Both solutions significantly prolonged the mean and total duration per hour of contractile states in the proximal, middle, and distal colon. The dogs began to leak fluid stools in squirts approximately 40-80 min after the start of perfusion. This type of incontinence was not associated with any specific type of motor activity. Infrequently, giant migrating contractions occurred during perfusion and caused explosive diarrhea. The migrating motor complexes remained disrupted during the 3-h postperfusion period. However, on the next day, the empty colon exhibited normal migrating motor complexes. The frequency of giant migrating contractions during perfusion and in the empty colon was significantly greater than that in the normal uncleansed colon. The total duration per hour of colonic motor activity in the empty colon was also greater than that in the normal uncleansed colon. We conclude that excessive fluid in the colon significantly alters its motor pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of fractionated doses of ionizing radiation on colonic motor activity.

The colonic motor effects of fractionated irradiation were studied in five conscious dogs. Seven colonic and two ileal strain gauge transducers were implanted. After control recordings, an abdominal dose of 250 cGy was administered three times a week on alternate days for three successive weeks (total dose 2,250 cGy). Recordings were then continued for 3 wk after the completion of radiation. Colonic giant migrating contractions (GMCs) occurred at a frequency of 0.15 +/- 0.05 contractions/h in the control state. Only one of these contractions (8.3%) originated in the small bowel and propagated into the colon. Abdominal field irradiation significantly increased the incidence of colonic GMCs to 0.51 +/- 0.11 contractions/h (P < 0.05). Fifty-four percent of GMCs originated in the small intestine. GMCs during the radiation schedule were associated with explosive diarrhea on seven occasions. Irradiation did not alter the frequency of colonic migrating motor complexes, but the mean duration of contractile states decreased in the middle and distal colon. Diarrhea occurred as early as the second dose of radiation. Pathological changes in the colon were correlated with motor activity. Both small intestinal and colonic GMCs reverted to control frequencies after cessation of radiation exposure. Abdominal irradiation significantly altered the contractile activity of the colon. These changes are associated with abdominal cramping and diarrhea.

Animals

Myogenic mechanism for peristalsis in opossum smooth muscle esophagus.

We studied the propagation of phasic contractions initiated by tetraethylammonium (TEA, 1-10 mM), high K+ concentration (10-30 mM), and bethanechol (10(-6) to 10(-2) M) in a whole organ in vitro preparation of the opossum smooth muscle esophagus. TEA initiated phasic contractions that began at all sites along the smooth muscle esophagus and propagated in both directions with a velocity similar to that of primary peristalsis. Blockade of neural transmission by tetrodotoxin (TTX, 10(-7) M) did not prevent contraction propagation. Although a majority of contractions initiated by TEA did not propagate the full length of the esophageal specimen, with the addition of TTX most contractions initiated by TEA did propagate the full specimen length in either direction. High K+ concentration and bethanechol elicited propagated contractions similar to those initiated by TEA. We conclude that 1) a myogenic mechanism exists for propagation of contractions along the smooth muscle esophagus and 2) intramural inhibitory nerves modulate the extent of myogenic propagation in the ascending as well as descending direction. We suggest that esophageal peristalsis may occur by myogenic propagation of contractions that are normally initiated in the proximal smooth muscle esophagus by excitatory nerves. Intramural inhibitory nerves may inhibit retrograde propagation as well as mediate descending inhibition in advance of the peristaltic wave.

Animals

The role of adrenergic receptors in the initiation of vomiting and its gastrointestinal motor correlates.

We investigated the role of adrenergic receptors in the mechanisms of initiation of vomiting and its gastrointestinal (GI) motor correlates. The effects of clonidine, UK-14304, St-91, naphazoline, phenylephrine and isoproterenol were examined for their ability to initiate vomiting and its GI motor correlates. Only the alpha-2 adrenoceptor agonists UK-14304, clonidine, St-91 and naphazoline activated vomiting and its GI motor correlates. Tolerance of vomiting, but not its GI motor correlates, readily developed to all alpha-2 adrenergic receptor agonists but St-91. The responses to UK-14304 or clonidine were blocked by idazoxan, yohimbine, clonidine tolerance or high doses of phenoxybenzamine, but not by propranolol or prazosin. The responses to UK-14304 or clonidine were also blocked by fentanyl, 1-(1-naphthyl) piperazine, methysergide, SCH 22390 or scopolamine, but not by haloperidol, sulpiride, domperidone or naloxone. Adrenoceptor antagonists, clonidine tolerance or sympathetic blockade did not block vomiting or its GI motor correlates activated by apomorphine, CuSO4 or cholecystokinin-octapeptide. We concluded that alpha-2 adrenergic receptors of the chemoreceptive trigger zone can initiate vomiting and its GI motor correlates, but these receptors do not mediate vomiting induced by another chemoreceptive trigger zone stimulant, apomorphine, or stimulation of the GI tract using CuSO4. However, 5-hydroxytryptamine-2 serotonergic, muscarinic cholinergic and opiate receptors within the central nervous system participate in controlling emesis activated by alpha-2 adrenergic agonists. Peripheral adrenergic receptors do not mediate the GI motor correlates of vomiting.

Adrenergic alpha-Agonists

Physiology and pathophysiology of colonic motor activity (2).

The basic motor function of the colon is to mix and knead its contents, propel them slowly in the caudad direction, hold them in the distal colon until defecation, and provide a strong propulsive force during defecation. Infrequently, it also produces mass movements in the proximal colon. These motor functions are achieved in most species by three different types of contractions: the individual phasic contractions that include the short- and long-duration contractions, organized groups of contractions that include the migrating and nonmigrating motor complexes, and special propulsive contractions (giant migrating contractions). The spatial and temporal patterns of all of these contractions are controlled by myogenic, neural, and chemical control mechanisms. The individual phasic contractions are highly disorganized in time and space in the colon. For this reason, they are effective in mixing and kneading and slow distal propulsion. The underlying cause of the disorganization of short duration contractions is the irregularity in the frequency and waveshape of colonic electrical control activity and its phase unlocking throughout the colon. The individual contractions in many species occur in cyclic bursts called contractile states. At least in some species, these contractile states exhibit mostly caudad and sometimes orad migration. However, there are also nonmigrating or randomly migrating contractile states in the colon. These two patterns of contractile states are called colonic migrating motor complexes and colonic nonmigrating motor complexes, respectively. The giant migrating contractions provide the strong propulsive force for defecation and mass movements. The neural control of colonic contractions is organized at three levels--enteric, autonomic, and central. The enteric nervous system contains cholinergic and peptidergic neurons and plays a major role in the control of colonic contractions. The autonomic nerves, the vagi, pelvic, lumbar colonic, hypogastric, and splanchnic nerves, seem to continuously monitor the state of the colon and provide a modulatory input when necessary. These nerves play a major role in the reflexive control of colonic motor function. The voluntary input from the central nervous system coordinates the motor activity of the colon, rectum, anal canal and sphincters for orderly evacuation of feces during defecation. The role of acetylcholine, nonadrenaline, and the yet to be completely identified nonadrenergic, noncholinergic neurotransmitter, possibly VIP, in the control of contractions is fairly well established. Besides these, there are several other peptides and chemicals that are localized in the colonic wall; their physiological roles remain unknown. Colonic motor activity has been studied in several disease states. The findings have not always been consistent.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging

Colonic motor activity in acute colitis in conscious dogs.

The changes in motor activity of the colon during acute colitis were investigated in six conscious dogs. The motor activity was recorded with seven strain-gauge transducers. Colitis was induced in the entire colon by luminal perfusion of acetic acid. The dogs exhibited urgency and diarrhea with mucus and blood during colitis. The mucosa was diffusely erythematous and friable and there were scattered ulcerations over the mucosal surface. The motor activity of the colon changed in several ways during colitis: (a) the total duration per hour and the mean duration of contractile states decreased significantly; (b) the cycle length of colonic migrating motor complexes was significantly prolonged, and the nonmigrating motor complexes were almost completely absent; and (d) the incidence of giant migrating contractions increased significantly. About half of the giant migrating contractions were followed by defecation. The remaining expelled mucus or gas. Sometimes, a migrating motor complex in the colon was also followed by defecation; this was never observed in the normal state. The motor activity of the colon was still decreased and the cycle length prolonged 21 days after induction of colitis. However, the dogs were asymptomatic at this time and the mucosa looked normal at colonoscopy. The incidence of giant migrating contractions was also normal at this time. It was concluded that the dog is a good model for the study of colitis because of the similarity of symptoms with human ulcerative colitis. The phasic contractions of the colon decreases during colitis but the incidence of giant migrating contractions is increased. The diarrhea in colitis may primarily be due to the large number of giant migrating contractions in the middle and the distal colon.

Acute Disease

Gastrointestinal motor effects of erythromycin in humans.

The effects of an antibacterially effective IV dose of erythromycin on gastrointestinal motor activity were investigated in eight normal healthy human volunteers in the fasted state and the fed state. Motor activity was recorded by a multilumen manometric tube. Data were analyzed visually and by a computer method. Blood samples were obtained for erythromycin and motilin assays. In the gastric antrum, erythromycin significantly increased the total duration, amplitude, and area under contractions from 0 to 60 minutes and frequency of contractions from 0 to 30 minutes from the start of its infusion in the fasted state. A similar response in the fed state occurred mostly from 0 to 30 minutes after the start of erythromycin infusion. By contrast, erythromycin inhibited the frequency and decreased the duration of small intestinal contractions in the fed state but had no effect in the fasted state. The gastric motor response was related to the plasma concentration of erythromycin, but not to plasma motilin. Erythromycin significantly shortened the duration of migrating motor complex disruption by a meal. Erythromycin also induced symptoms of upper abdominal pain, bloating, and nausea. Abdominal pain was related to strong antral contractions in both fasted and fed states; bloating occurred only in the fed state. Nausea occurred in both fasted and fed states, but it was not related to any specific pattern of motor activity. It is concluded that the strong antral contractions induced by erythromycin may accelerate the rate of gastric emptying, but they may also be responsible for causing the sensations of upper abdominal pain and bloating. The motor response to erythromycin is less during the fed than during the fasted state. The strong antral contractions induced by erythromycin are not mediated by the release of motilin.

Abdominal Pain

Colonic motor response to a meal in acute colitis.

The symptoms of urgency, diarrhea, and abdominal discomfort are exaggerated after a meal in inflammatory disorders of the colon, such as ulcerative colitis. The possible motor correlates of these symptoms were investigated in a model of acute colitis in six dogs. Each dog was instrumented with seven strain gauge transducers, two on the proximal, three on the middle, and two on the distal colon. After an overnight fast, 4-hour fasted recordings were made from the normal colon and after the colon had been cleansed on the previous day with Colyte (Reed & Carnrick, Piscataway, NJ). A 1300-kcal meal was then fed, and the recordings were continued for another 8 hours. Acute colitis was then induced by the perfusion of 10 mL of 75% acetic acid and confirmed with colonoscopy and biopsy. The fasted and postprandial recordings were repeated during the next 5 days. In the control state, ingestion of the meal increased the total duration per hour of contractile activity in the early (0-2 hours) and late (2-8 hours) postprandial periods in the distal colon. In the proximal and the middle colon, a significant increase in motor activity occurred only during the late postprandial period. Similar effects were observed in the cleansed colon. By contrast, there was no significant increase in motor activity after a meal during colitis in any of the postprandial periods in the cleansed or the uncleansed colon. During colitis, there was a significant increase in the incidence of giant migrating contractions in the fasted state. The ingestion of a meal further increased the frequency of giant migrating contractions in the uncleansed colon from 0.4 +/- 0.1 to 1.3 +/- 0.5 per hour in the late postprandial period. There was no significant increase during the early postprandial period. The increase in the late postprandial frequency of giant migrating contractions was associated with an increase in defecation frequency. It is concluded that the motor response of the colon to a meal is absent in acute colitis. The entry of new ingesta into the colon during the late postprandial period stimulates enteric mechanisms to initiate an excessive number of giant migrating contractions. These giant migrating contractions may be related to increased postprandial abdominal discomfort and increased frequency of defecation.

Acute Disease

Trichinella spiralis infection alters small bowel motor activity in the fed state.

The effect of Trichinella spiralis infection on small intestinal transit and motor activity in the fed state during the intestinal phase of infection was studied. Contractions were recorded by strain gauge transducers, and mean transit time was measured by marker dilution technique. The mean amplitude and area of individual phasic contractions decreased, but no change occurred in their mean duration during trichinosis. The total amplitude and area of phasic contractions also decreased; this was caused by a decrease in the frequency of contractions as well as a decrease in the mean parameters. The reduction in the total duration was entirely caused by the decrease in frequency. The reduction in the total parameters of all contractions was the result of a reduction in the same parameters for both propagating and nonpropagating contractions. However, the decrease in the parameters of propagating contractions was much greater. Also, there was a decrease in the distance of propagation of phasic contractions. The transit time as a result of phasic contractions increased during T. spiralis infection. Additionally, T. spiralis infection induced giant migrating contractions in the fed state that were never observed during control. Chyme was propelled very rapidly and effectively by giant migrating contractions. The findings of the present study suggest that during diarrhea induced by T. spiralis infection, the phasic contractions may act to decrease transit and, hence, allow more contact time for absorption of water and nutrients. However, this response may be counter-balanced by giant migrating contractions that rapidly propel chyme into the colon and compound the diarrhea associated with T. spiralis infection.

Animals

Effects of physical exercise on colonic motor activity.

We investigated the effect of physical exercise on colonic motor activity in the fasted and fed states in six conscious dogs. Each dog was implanted with nine strain gauge transducers: three on the proximal, three on the middle, and three on the distal colon. The dogs ran for 1 h on a treadmill at 5 km/h (slope 5%). In the fasted state, the dogs exercised during the 5th h of recording after an overnight fast, and in the fed state during the 1st, 3rd, and 5th postprandial hour. In the fasted state, exercise significantly decreased the frequency of colonic migrating motor complexes (MMCs) but had no effect on the total or the mean duration of contractile states in the proximal, middle, and distal colon. Postprandially, exercise disrupted colonic MMCs and replaced them with nonmigrating motor complexes in all three periods of exercise (1st, 3rd, and 6th h). Exercise also increased the total duration per hour of contractile activity throughout the colon during the 1st and 3rd h and only in the distal colon during the 6th h after the meal. The dogs never defecated during rest in the fasted or the fed state. Shortly after the start of exercise in the fasted and fed states, giant migrating contractions (GMCs) occurred, and they were followed by defecation. In approximately 40% of the experiments, another GMC originated in the proximal colon, approximately 10 min after the first defecation, and migrated caudad up to the middle colon. These GMCs were not associated with defecation but caused mass movements.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Myogenic oscillatory mechanism for opossum esophageal smooth muscle contractions.

We evaluated the control of phasic contractions in opossum esophageal circular smooth muscle by determining the contractile response in vitro to agents that cause membrane depolarization and excitation by different mechanisms. Transverse muscle strips taken from different sites along the length of the smooth muscle esophagus were exposed to progressively increasing concentrations of tetraethylammonium (1-30 mM), K+ (4.6-30 mM), or bethanechol (10(-6) to 10(-2) M). In normally inactive esophageal circular smooth muscle, tetraethylammonium and high K+ concentration elicited phasic contractions that were not blocked by atropine and tetrodotoxin. Bethanechol, an M2 muscarinic receptor agonist that acts selectively on smooth muscle, elicited phasic contractions that were not blocked by tetrodotoxin. We conclude that a latent myogenic oscillatory mechanism for control of phasic contractions exists in esophageal circular smooth muscle and that it may be activated by nonspecific excitation of the smooth muscle membrane. We suggest that this myogenic oscillatory mechanism is likely excited and modulated by nerves.

Animals