Changes in nutritional status associated with obstructive jaundice and biliary drainage in rats.

Effect of bile duct ligation (BDL) and internal biliary drainage on food intake and nutritional status was studied in rats and compared with sham and pair-fed animals. During week 1, food intake of BDL animals was reduced (p less than 0.05), resulting in weight loss (p less than 0.05). In weeks 2 and 3, food intake, nitrogen balance, and weight gain were similar in all groups. Internal biliary drainage or sham operation after 3 wk produced transient changes in food intake and N2 balance. Serum albumin fell in all groups, returned to normal in sham (3.2 +/- 0.1 g/dl) and pair-fed (3.1 +/- 0.1 g/dl), but persisted in BDL rats (2.4 +/- 0.2 g/dl, p less than 0.001). Jaundice was associated with anemia. Although BDL produces transient changes in food intake, weight gain, and N2 balance, anorexia and malnutrition are not features of this animal model. Nutritional risk factors associated with hyperbilirubinemia are probably due to changes in intermediary metabolism.

Post-injury multiple organ failure: the role of the gut.

Despite intensive investigation, the pathogenesis of post-injury multiple organ failure (MOF) remains elusive. Laboratory and clinical research strongly suggests that the gastrointestinal tract (i.e., the gut) plays a pivotal pathogenic role. Since its inception in 1988, the Trauma Research Center (TRC) at the University of Texas-Houston Medical School (UTHMS) has focused its efforts on elucidating the role of the gut in post-injury MOF. On the basis of our observations and those of others, we believe that 1) shock with resulting gut hypoperfusion is an important inciting event, 2) the reperfused gut is a source of proinflammatory mediators that can amplify the early systemic inflammatory response syndrome (SIRS) and thus contribute to early MOF, 3) early gut hypoperfusion causes an ileus in both the stomach and small bowel that sets the stage for progressive gut dysfunction so that the proximal gut becomes a reservoir for pathogens and toxins that contribute to late sepsis-associated MOF, and 4) late infections cause further worsening of this gut dysfunction. Thus, the gut can be both an instigator and a victim of MOF. The purpose of this article is to provide the rationale behind these beliefs and to provide a brief overview of the ongoing research projects in the TRC at UTHMS.

Focal microcirculatory changes during the production of aspirin-induced gastric mucosal erosions.

Ischemia of the gastric epithelium has emerged as one of the more likely mechanisms for gastric ulceration. Radiolabeled microspheres (15 mu) were used to measure blood flow to exteriorized, chambered stomach segments in eight dogs during the development of aspirin erosions. Flow determinations were made before aspirin (20 mM in 140 mM HCl) exposure and at 2, 10, and 20 minutes after the initiation of the chemical insult. Lesions formed at 30 minutes of acetylsalicylic acid exposure. The epithelium was separated into normal and injured, based on gross discoloration caused by intramucosal hemorrhage. The calculated blood flows to the abnormal and normal mucosa were identical at 2 minutes (0.22 +/- 0.04 versus 0.15 +/- 0.03, NS) and at 10 minutes (0.39 +/- 20 versus 0.17 +/- 0.04, NS) after initiation of aspirin injury (all values in ml/gram-wet weight/min, mean +/- SEM). By 20 minutes of aspirin exposure, mucosal blood flow to areas that eventually became injured was greater than the blood flow to areas that remained normal (0.45 +/- 0.12 versus 0.13 +/- 0.05 P less than 0.05). The data suggest that ischemia does not play a role in chemical erosive gastritis.

Role of pancreatic duct occlusion with prolamine (Ethibloc) in necrotizing pancreatitis.

There is evidence that the pancreatic duct plays an important role in the evolution of necrotizing pancreatitis. We hypothesized that occlusion of the pancreatic duct and its smaller ductules with prolamine (Ethibloc) in opossums at risk of severe necrotizing pancreatitis would have a beneficial effect on the progression of the disease. Sixteen opossums underwent bile duct ligation below the entrance of the pancreatic duct. They were divided into four groups at 6 days. Group I (control, n = 5) opossums were killed for histologic observation of the degree of necrosis of the pancreas; group II (n = 5) underwent external drainage of the pancreatic biliary duct; group III (n = 4) had external biliary drainage and ligation of the pancreatic duct; group IV (n = 7) was treated with external biliary drainage and ligation of the main pancreatic duct after instillation of prolamine. Serum amylase, lipase, and calcium values were determined. The pancreas was examined by inspection and histologically at the time of death, and the severity of the disease was determined by quantitation of pancreatic tissue necrosis. All animals in groups II and III died 8 to 14 days after bile duct ligation, and all had severe necrotizing pancreatitis. All animals in group IV survived and were killed at 2 to 10 weeks after prolamine (Ethibloc) injection into the pancreatic duct. A mild edematous pancreatitis was observed in all seven animals. Prolamine (Ethibloc) provided dramatic protection from progressive necrosis. This study does not provide an explanation, but it allows for speculation that ductal injection interrupted the deleterious effect of proteolytic enzymes and their leakage into the interstitial space of the pancreas.

A new method for correlating pancreatic and biliary duct pressures and sphincter of Oddi electromyography.

Myoelectric activity of the sphincter of Oddi and duodenum was correlated with pancreatic and biliary duct pressures in eight opossums, in both the fasted and fed states. Four bipolar electrode pairs were implanted in the sphincter of Oddi and duodenum. A polyethylene T tube was placed in the pancreatic duct. The common duct was cannulated through a small bile duct. This method allowed pressure recording for several weeks and avoided interference with the flow of bile or pancreatic juice into the duodenum. The frequency of slow waves was the same in the sphincter of Oddi and duodenum (19 per minute). The variation in the frequency of spike potentials in the sphincter of Oddi correlated to that of the migrating myoelectric complex in the duodenum. The average frequency of slow waves that have superimposed spike potentials in the sphincter of Oddi and duodenum was 3.0 and 0 in phase 1, 4.7, and 6.2 in phase II, 6.1 and 15.1 in phase III, and 3.4 and 6.3 in phase IV, respectively. The average duration of a migrating myoelectric complex cycle was 92 minutes. After feeding, the interdigestive phases of the migrating myoelectric complex were abolished and substituted by a feeding activity pattern that was characterized by an average number of sphincter of Oddi and duodenum spikes of 6.6 and 10.7, respectively. The mean fasting pressure in the pancreatic and biliary duct was 15 and 13 mmHg, respectively. Pressure changes were of two types--synchronous with respiratory movements and with each sphincter of Oddi spike potential. There was no variation in the baseline pressure during the migrating myoelectric complex phases and the fed state. It is concluded that the sphincter of Oddi of the fasting opossum exhibits cyclic changes in the number of spike potentials that correlate with the migrating myoelectric complex in the duodenum. However, the number and amplitude of spike potentials are different in the sphincter of Oddi and duodenum. There is no change in the baseline pressure during fasting and feeding states, and a temporary pressure elevation synchronic with each sphincter of Oddi spike potential was observed.

Effect of aspirin, bile salt, and ethanol on canine gastric mucosal blood flow.

The effect of aspirin (20 mM.), sodium taurocholate (40 mM.), and ethanol (24 per cent w/v) on gastric mucosal blood flow was studied in an exteriorized, chambered preparation of canine fundic stomach. Gastric mucosal blood flow was measured by gamma-labeled microspheres and plasma aminopyrine clearance. All three test solutions caused a significant increase in microsphere-measured mucosal blood flow. The degree of increase in gastric mucosal blood flow was proportional to the severity of gross mucosal injury, being greatest with bile salt and least with ethanol. Plasma aminopyrine clearance determined only a small fraction of mucosal flow measured by microspheres following injury, particularly in sodium taurocholate and ethanol experiments, where the net hydrogen ion back diffusion was greatest. The results suggest that increased gastric mucosal blood flow may be a secondary defensive response to the damage caused by these irritants and that the plasma aminopyrine clearance is unreliable in quantitating mucosal blood flow changes in the presence of mucosal injury.

Direct effect of endotoxin on the gastric mucosal microcirculation and electrical gradient.

The effects of intra-arterial infusion of E. coli endotoxin at 1.0 mg. per minute on the gastric total and mucosal blood flows, electrical potential difference, and ionic fluxes across the gastric mucosa were studied in an exteriorized, chambered preparation of canine fundic stomach. Gamma-labelled microsphere technique was used in addition to venous drainage and plasma aminopyrine clearance for the measurement of total and mucosal blood flow, respectively. In spite of normal systemic blood pressure throughout the experiment, E. coli endotoxin infusion caused a significant decrease in total gastric blood flow and in the fractional distribution of flow to the mucosae. There was no significant arteriovenous shunting of microspheres. Significant reduction in potential difference and hydrogen-ion back diffusion also was noted after endotoxin infusion, possibly as a consequence of reduced mucosal blood flow. The results indicate that significant gastric mucosal ischemia can occur and may represent a mechanism in the development of gastric erosions in endotoxemia, even in the absence of systemic hypotension.

Myoelectric control of gastrointestinal and biliary motility: a review.

The movement of ingested food and secretions through the gastrointestinal and its appendages depends on a highly integrated and coordinated response of the smooth muscle contained within the wall of the gut. This review will consider, in detail, the various myogenic factors that contribute to the usual aboral propulsion of the gastrointestinal contents. The role of myoelectrical complexes as represented by slow waves and spike potentials are emphasized, for they appear to play a central role in the initiation of sphincter function and gastrointestinal peristalsis. The myoelectric control of the sphincter of Oddi is discussed in relationship to gastroduodenal motility, since disturbances in this finely modulated sphincter may lead to biliary-pancreatic dysfunction and symptoms of upper gastrointestinal disease.

Controlled intragastric pH and cimetidine inhibition of histamine-stimulated gastric acid secretion in the dog.

This study tested a circulating intragastric titration system with an examination of the kinetics of cimetidine inhibition of histamine-stimulated gastric acid secretion of pH 7.0. Dogs were anesthetized, intubated with a biluminal nasogastric device, and connected to the titrating system. The dogs were stimulated with histamine at 0.0, 0.25, 0.50, 1.0, 2.0, and 4.0 microgram/kg/min IV. The dose variations were repeated on separate days with cimetidine infusion at 0.0, 20, and 40 microgram/kg/min IV. Calculated maximal response was 4.52 mEq/kg/hr. Histamine D50 was 0.60 microgram/kg/min. Cimetidine ID50 was 22.6 microgram/kg/min when histamine was given at 1.0 microgram/kg/min. Although acid secretion was higher than other published values, cimetidine inhibition kinetics were not significantly different from published values. A positive correlation was found between cimetidine ID50 and the logarithm of the histamine infusion rate. Our data suggest that (1) a simple circulating intragastric titration system can give accurate results in acid secretion studies, (2) increased gastric pH may enhance histamine-stimulated acid secretion, (3) neutralization of gastric contents does not interfere with cimetidine inhibition kinetics which is competitive, and (4) at artifically high rates of histamine infusion, cimetidine can actually increase acid secretion. We suggest that a circulating intragastric system may be tested in a surgical intensive care unit to evaluate potential clinical value in antiulcer therapy.

Weight loss and metabolic changes of morbidly obese patients after gastric partitioning operation.

UNLABELLED: Weight loss, alterations in basal metabolic rate, and utilization of body fat, carbohydrate, and protein substrates were studied in nine patients before operation and 3 and 12 months after gastric partitioning operation for morbid obesity. Respiratory oxygen consumption and carbon dioxide excretion measurements were taken three consecutive mornings by the open circuit-Scholander technique. Measurements of urine urea nitrogen were made from 24-hour urine collections. Basal metabolic rate and utilization of fat, carbohydrate, and protein were calculated in kilocalories per minute by indirect calorimetry. Initial body weight was 124.5 +/- 19.0 kg (mean +/- SD). The weight losses between measurements at months 0 and 3 and at months 3 and 12 were 20.8 +/- 4.6 kg and 2.7 +/- 8.4 kg, respectively. Total weight loss between months 0 and 12 was 23.5 +/- 8.3 kg (19.3% +/- 7.4%). At 3 months the fraction of basal metabolic rate contributed by carbohydrate (p less than 0.05) and protein (p less than 0.01) utilization decreased significantly, while that contributed by fat increased (p less than 0.05). Between months 0 and 12 there was no significant difference in protein or carbohydrate utilization, but fat utilization increased (p less than 0.10). CONCLUSIONS: Gastric partitioning operation resulted in an initial rapid body weight loss over 3 months with a sustained reduction over 1 year; there was a metabolic utilization shift to fat with carbohydrate and protein sparing; no metabolic parameter was predictive of weight loss; and temporally, the rapid weight loss was paralleled by a significant metabolic utilization shift, and the sustained loss was paralleled by a stabilization of this shift.

A model of biliary pancreatic reflux.

A primate model for the study of biliary pancreatic reflux under relatively physiological conditions is described. Cannulas were inserted into the gallbladder and the common bile duct of rhesus monkeys, and a pedicled segment of small bowel was used to create a pancreaticocutaneous fistula after resection of the spleen and pancreatic tail. Following recovery, Hypaque was instilled into the gallbladder with maintenance of common duct pressure within a normal range. The pancreatic duct was visualized in 21 of 34 radiographic studies (19 monkeys). Small amounts of iodine were detected in the fistula effluent of nine of 11 animals that refluxed radiologically. Radioactive polyethylene glycol (PEG-C14) was instilled into the gallbladder and pancreatic fistula drainage sampled by aspiration (26 studies, four monkeys). When compared to controls without PEG instillation (six studies, four monkeys), there was a significant rise in fistula counts beginning 50 minutes after injection and peaking at 180 minutes. In a second series of studies, pancreatic fistula aspiration was replaced by a flush technique using a triple-lumen cannula which allowed constant monitoring and control of fistula pressure. A statistically significant rise and fall of radioactivity after PEG introduction again was demonstrated. These data demonstrate taht biliary pancreatic reflux can occur and be quantitated under these experimental conditions.

The role of biliary obstruction in the pathogenesis of acute pancreatitis in the opossum.

Pancreatitis was induced in the opossum by occluding the common bile duct above or below the entrance of the pancreatic duct. The common channel theory was tested by evaluating the effect of preligation of the pancreatic duct to prevent the reflux of bile after ligation of the distal common duct. The severity of the disease was determined by histologic grading of the degree of pancreatic tissue necrosis. Serum amylase, lipase, and calcium were determined. Concomitant obstruction of the biliary and pancreatic ducts produced severe necrotizing pancreatitis whether or not bile reflux was present. Pancreatic ductal obstruction alone was associated with acinar atrophy and mild interstitial pancreatitis. Biliary obstruction alone above the entrance of the pancreatic duct resulted in marked hyperemia of the gland but without histologic evidence of pancreatic inflammation. A positive bacterial culture of the pancreas was obtained in only four of 36 opossums in a distribution to suggest random contamination. There was an inverse correlation between calcium levels and the degree of tissue necrosis. This study demonstrates that biliary obstruction rather than bile reflux into the pancreas is a requisite for the pathogenesis of severe biliary pancreatitis in this model.

Gallbladder and gastrointestinal motility after hemorrhagic shock.

The alterations in fasting gallbladder and gastrointestinal motility during hemorrhagic shock were investigated. Eight opossums implanted with a gallbladder cannula, gastrointestinal bipolar electrodes, and a carotid catheter were subjected to hemorrhagic shock of 30 mm Hg for 60 minutes by the removal of arterial blood. Shed blood was reinfused after the shock period. Fasting gallbladder volume and gastrointestinal electrical activity were studied before, immediately after, and 24 hours after hemorrhagic shock. Control measurements demonstrated a slow-wave frequency maximal in the duodenum (18.1 +/- 1.1 waves/min), with a plateau in the proximal third of the small bowel, decreasing thereafter. The migrating motor complex (MMC) had a duration of 118 +/- 28 minutes. The average volume of the gallbladder before shock was 5.4 +/- 1.5 ml. Gallbladder volume fluctuated with the MMC, being maximal during phase I and minimal in phase III. The volume of blood removed to reduce mean arterial pressure to 30 mm Hg was 45 +/- 5 ml/kg. Immediately after the shock and blood reinfusion, slow-wave frequency decreased by 40% in the antrum and 25% in the small bowel. The MMC was of shorter duration (91 +/- 22 minutes; p less than 0.05), and gallbladder volume increased to 7.0 +/- 1.7 ml (p less than 0.05). Fluctuations in gallbladder volume during the MMC were absent. Twenty-four hours after shock, slow-wave frequency, MMC, and gallbladder volume had returned to normal and were not different from control measurements. Ischemic damage to the gastrointestinal tract is postulated as the cause of gallbladder dysfunction and altered intestinal motility after hemorrhagic shock.

Changes in body composition and dietary intake after gastric partitioning for morbid obesity.

Patients who undergo gastric partitioning for morbid obesity lose weight rapidly in the first year after surgery. This study measured changes in body composition and dietary intake at 3 months, 6 months, and 1 year after gastric partitioning. Body composition was determined by total-body gamma-ray spectrometry. Records of dietary intake were computer analyzed for nutritional content with the Ohio State Nutrient Analysis Data Base. All patients lost a significant amount of weight at 3, 6, and 12 months after surgery. Loss of lean tissue comprised 25% of the total weight loss at 3 months but only 20% of the total at 1 year. Before surgery the mean energy intake was 2592 kcal and the mean protein intake was 92 gm. After 3 months, energy intake was 745 kcal and protein 32 gm. One year after surgery energy intake was 1089 kcal and protein 41 gm per day. We conclude that patients lose a significant amount of lean body tissue in the first 3 months after gastric partitioning but the loss does not continue, and 1 year after surgery some lean tissue is actually regained. This initial loss is due to a combination of a very restrictive dietary regimen and the body's metabolic response to surgery. After the first 3 months adaptation occurs and lean tissue is spared.

Multifactor evaluations of surgical trainees and teaching services.

Surgical education has been exposed to increasing challenges as students have moved from the highly structured environment of a university hospital into a variety of clinical settings within the community. Presented with a general surgical service that uses ten relatively autonomous teaching services in seven hospitals, we have developed a computer-based evaluation system designed to provide quality control and a feed-back loop for trainee, teacher, and service. Trainees were rated by comparing them to their peers, with the chief resident as a reference standard. Profiles of each teaching service also were developed and compared one to the other. The results of both studies over a one year period are presented.

Estimation of hepatic blood flow by hydrogen gas clearance.

The hydrogen gas clearance technique was evaluated to estimate regional hepatic blood flow. Initially, the H2 gas method was compared to the indocyanine green clearance in mini pigs. The blood flow measured by the H2 gas method (0.49 +/- 0.03 ml/min/gm) was only 39% of the calculated blood flow by the indocyanine green method (1.26 +/- 0.14 ml/min/gm). The blood flow determined by H2 gas decreased to 0.06 +/- 0.04 ml/min/gm after ligation of the hepatic artery. No difference in blood flow was found by simultaneous measurements on the left (0.89 +/- 0.1 ml/min/gm) and right (0.96 +/- 0.13 ml/min/gm) liver lobes in rats. After ligation of the left hepatic artery in the rats, a delayed response to H2 application was present and the determined blood flow (0.14 +/- 0.02 ml/min/gm) was significantly reduced (p less than 0.001) compared with the right liver lobe H2 determined blood flow as a control. No current was generated after ligation of the left hepatic artery and the portal vein indicating that there was no blood flow measured by the gas H2 method. The results indicate that the H2 gas clearance technique may be a method that assesses hepatic arterial liver perfusion rather than estimates total hepatic blood flow. The safety and simplicity of the H2 gas clearance technique may make it suitable for clinical application in serial measurement of hepatic arterial blood flow in man.

Gallbladder contractility and mucus secretion after cholesterol feeding in the prairie dog.

The purpose of our study was to evaluate changes in gallbladder contractility and mucus secretion in vitro during the early stages of gallstone formation in prairie dogs. Thirty-two animals were divided into five groups. Control animals were fed a trace cholesterol diet. Experimental animals were fed a high-cholesterol diet for 3, 6, 8, and 14 days, respectively. Muscle stress was measured in response to cholecystokinin octapeptide in each of the groups. The maximal stresses in the 8-day diet (68 +/- 7 gm/cm2) (mean +/- SEM) and 14-day diet animals (83 +/- 7 gm/cm2) were found to be significantly lower than those of the control animals (137 +/- 12 gm/cm2). The stress in 3-day diet animals was significantly greater (224 +/- 23 gm/cm2). A significant increase in mucus secretion was observed only in 14-day diet animals (11.0 +/- 0.5 X 10(6) dpm/gm dry wt) compared with the control animals (6.4 +/- 1.0 X 10(6) dpm/gm). The decrease in contractility may be the initial event in cholesterol stone formation, and the prolonged exposure of the gallbladder epithelium to crystals may stimulate the release of mucus into the bile.

Effects of gastrointestinal hormones on Oddi's sphincter and duodenal myoelectric activity and pancreatobiliary pressure. Studies in the opossum.

Myoelectric activity of Oddi's sphincter and duodenum was correlated with common duct and pancreatic duct pressures in conscious opossums after infusion of the following substances: cholecystokinin, pentagastrin, glucagon, secretin, and acetylcholine. Cholecystokinin and pentagastrin increased and glucagon and secretin decreased the frequency of spike potentials in Oddi's sphincter and the duodenum. Acetylcholine was associated with the largest increase in spike potentials in both Oddi's sphincter and the duodenum. Although there was variation in the number of pressure elevations related to Oddi's sphincter spike potentials, the baseline pressure remained constant during administration of the hormones. Acetylcholine infusion increased the biliary and pancreatic pressures to 29 and 31 mm Hg, respectively. We conclude that gastrointestinal hormones may have an important role in regulating the excretion of bile and pancreatic juice into the duodenum.

Aberrant biliopancreatic duct. A probable cause of acute pancreatitis?

Abnormal biliopancreatic ducts are very uncommon in adults with the exception of those associated with abnormalities of either the pancreatic or the bile ducts. The case presented herein is unique in that a biliopancreatic connection occurred proximal to the papilla of Vater and the patient was symptomatic because of the aberrant connection. The surgical therapy consisted of cholecystectomy and ligation of the aberrant duct, with complete relief of severe, debilitating symptoms. This interesting clinical observation is discussed in the light of Opie's theory of biliary reflux into the pancreatic duct as a pathogenetic mechanism for acute pancreatitis.

The effect of preoperative internal and external biliary drainage on mortality of jaundiced rats.

Mortality following abdominal infection induced by cecal ligation and puncture was studied in rats with obstructive jaundice and after relief of the obstruction by preoperative internal or external biliary drainage. Four groups of adult Sprague-Dawley rats were used: common bile duct ligation (BDL), BDL followed by internal drainage after two weeks, BDL followed by external drainage after two weeks, and sham operation. The serum bilirubin concentration was significantly increased in the BDL group and returned to normal following internal and external drainage. Mortality in the sham group was 16.5% and increased to 83.3% following BDL, but it decreased significantly (25%) to near-normal values after preoperative internal drainage. However, after external drainage no significant reduction in mortality (63%) was found. These findings confirm the poor results of preoperative external drainage in previous studies and establish the efficacy of internal biliary drainage in a well-controlled experimental model that has to be evaluated in the clinical situation.