The feasibility of tricuspid annular plane systolic excursion performed by transesophageal echocardiography throughout heart surgery and its interchangeability with transthoracic echocardiography.

Tricuspid annular plane systolic excursion (TAPSE) is a robust measure of RV function, but the performance of transesophageal echocardiography (TEE) measured TAPSE during surgery is not well established. We aim to evaluate feasibility of various TEE views before, during and after surgery. Furthermore, we compare performance of individual TEE measurements depending on view and method (AMM- and M-mode as well as 2D) as well as TAPSE measured using TEE with transthoracic echocardiography (TTE) TAPSE. The study was conducted from January 2015 through September 2016. In 47 patients with normal left ventricular ejection fraction, TEE was prospectively performed during coronary artery bypass grafting surgery. TAPSE and tricuspid annulus tissue Doppler imaging (TDI) were recorded in five different views at pre-specified time points during surgery. Data were analyzed for availability (obtainable/readable images) and reliability (intra-/inter-observer bias and precision). Finally, TEE TAPSE was compared to TTE TAPSE immediately before and after surgery. TAPSE and TDI with TEE was achievable in > 90% of patients in the transgastric view during surgery. The AM- and M-mode had the best reliability and the best correlation with TAPSE measured with TTE. The deep transgastric view was achievable in less than 50% after sternotomy, and TAPSE measured from 2D had a poorer performance compared to the AM- and M-mode. TDI demonstrated a high reliability throughout surgery. RV function can be evaluated by TAPSE and TDI using TEE during surgery. TEE values from the transgastric view demonstrated high performance throughout surgery and a good agreement with TTE TAPSE measurements.

Indication for resuscitative thoracotomy in thoracic injuries-Adherence to the ATLS guidelines. A forensic autopsy based evaluation.

BACKGROUND: The appropriate indications for Resuscitative Thoracotomy (RT) are still debated in the literature and various guidelines have been proposed. This study aimed to evaluate whether Advanced Trauma Life Support (ATLS) guidelines for RT were applied correctly and to evaluate the proportion of deceased patients with potentially reversible thoracic lesions (PRTL). METHODS: The database at the Department of Forensic Medicine at Copenhagen University was queried for autopsy cases with thoracic lesions indicated by the SNOMED autopsy coding system. Patients were included if thoracic lesions were caused by a traumatic event with trauma team activation. Patient cases were blinded for any surgical intervention and evaluated independently by two reviewers for indications or contraindications for RT as determined by the ATLS guidelines. Second, autopsy reports were evaluated for the presence of PRTL. RESULTS: Sixty-seven patients met the inclusion criteria. Two were excluded due to insufficient data. The overall agreement with guidelines was 86% and 77% for blunt and penetrating trauma, respectively. For patients submitted to RT the overall agreement with guidelines was 63% being 45% and 74% for blunt and penetrating trauma, respectively. For patients who did not undergo RT the agreement with guidelines was 100%. In all cases where RT was performed in agreement between guidelines and the clinical decision the autopsy reports showed PRTL in 16 (84%) patients. In cases of non-agreement PRTL were found in 9 (82%) patients. CONCLUSIONS: Agreement with ATLS guidelines for RT was 63% for intervention and 100% for non-intervention in deceased patients with thoracic trauma. Agreement was higher for penetrating trauma than for blunt trauma. The adherence to guidelines did not improve the ability to predict autopsy findings of PRTL. Although the study has methodical limitations it represents a novel approach to the evaluation of the clinical use of RT guidelines.

Biliary diseases in heart transplanted patients: a comparison between cyclosporine A versus tacrolimus-based immunosuppression.

A cyclosporine (CsA)-based immunosuppression is associated with an increased incidence of cholelithiasis after heart transplantation. It is not known if tacrolimus (Tac) has comparable biliary side effects in humans. We evaluated the incidence of gallbladder sludge and cholelithiasis under Tac-based immunosuppression by ultrasound examinations in 31 cardiac transplants (25 male, 6 female, mean age: 59 ' 11 years). Data were compared to 57 patients (47 male, 10 female, mean age: 58 ' 11 years) who received CsA-based immunosuppression. 6 patients receiving Tac and 6 patients receiving CsA had already gallstones prior to transplantation so that finally 25 patients of the Tac group and 51 patients of the CsA group could be evaluated. In the Tac group the incidence of biliary sludge was 4% (1 of 25), of gallstones 28% (7 of 25). In comparison, patients receiving CsA developed biliary sludge in also 4% (2 of 51) and gallstones in 25% (13 of 51). Nine of 42 males in the CsA group (21%) and eight of 20 males in the Tac group (40%) developed either gallstones or sludge (n.s). Six of nine females in the CsA group (67%), but none of five females in the Tac group (0%) developed either gallstones or sludge (p = 0.01). In summary, the incidence of biliary disease in patients with Tac is comparable with CsA-based immunosuppression. We recommend regular sonographical examinations to detect biliary diseases as early as possible. In cases of clinically, laboratory and sonographical signs of cholecystitis cholecystectomy is indicated. It seems that towards lithogenicity female patients benefit more from a Tac-based treatment because the occurrence of gallstones is rare.

Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa.

OBJECTIVE: Ghrelin is a new gastric hormone that has been identified as an endogenous ligand for the growth hormone (GH) secretagogue receptor subtype 1a (GHS-R1a). Ghrelin administration however not only stimulates GH secretion but also induces adiposity in rodents by increasing food intake and decreasing fat utilization. We hypothesized that impaired ghrelin secretion in anorexia nervosa may be involved in the pathogenesis of this eating disorder. To examine this hypothesis and to further investigate the role for ghrelin in regulating energy homeostasis, we analyzed circulating ghrelin levels in patients with anorexia nervosa and examined possible correlations with clinical parameters before and after weight gain. METHODS: Plasma ghrelin levels were measured in overnight fasting plasma samples from 36 female patients with anorexia nervosa (age: 25.0+/-1.2 years, BMI: 15.2+/-0.2 kg/m(2)) before and after weight gain following psychotherapeutic treatment intervention in a psychosomatic institution. Plasma ghrelin levels were also measured in fasting plasma samples from 24 age-matched female controls (31+/-1.4 years, BMI: 22.9+/-0.45 kg/m(2)). For quantification of ghrelin levels a commercially available radioimmunoassay (Phoenix Pharmaceuticals, USA) was used. RESULTS: Fasting plasma ghrelin levels in anorectic patients were significantly higher (1057+/-95 pg/ml) than in normal age-matched female controls (514+/-63 pg/ml n=24, P=0.02). Therapeutic intervention in a psychosomatic institution caused an BMI increase of 14% (P<0.001) leading to a significant decrease in circulating ghrelin levels of 25%, (P=0.001). A significant negative correlation between Deltaghrelin and DeltaBMI was observed (correlation coefficient: -0.47, P=0.005, n=36). CONCLUSION: We show for the first time that fasting plasma levels of the novel appetite-modulating hormone ghrelin are elevated in anorexia nervosa and return to normal levels after partial weight recovery. These observations suggest the possible existence of ghrelin resistance in cachectic states such as caused by eating disorders. Future studies are necessary to investigate putative mechanisms of ghrelin resistance such as a possible impairment of intracellular ghrelin receptor signaling in pathophysiological states presenting with cachexia.

Interrelationships between the size of the pancreas and the weight of patients with eating disorders.

OBJECTIVE: Starvation severely affects normal pancreatic function in children suffering from Kwashiorkor and in animals undergoing food deprivation. This study examines whether pancreatic size, as determined by ultrasound, is dependent on starvation or on eating patterns in patients with eating disorders. METHOD: In 109 inpatients with eating disorders, 86 with anorexia nervosa and 23 with bulimia nervosa, we determined the pancreatic size by means of abdominal ultrasonography before increase in weight. Twenty-four inpatients with other psychiatric disorders served as controls. Pancreatic size was defined by the maximal diameter and the length of the head, the diameter of the head at the confluence of the splenic and mesenteric veins, and the diameters of the body and tail. In 41 eating disorder patients, pancreatic size was also measured during the course of therapy and increase in weight. RESULTS: Pancreatic size correlates highly with body mass index (BMI). Counteracting actions such as purging do not seem to influence this pathophysiologic finding. Dystrophy of the pancreas is reversible in a short period of time. The increase in pancreatic size after maintenance of a normal eating pattern, however, exceeded the size expected by regression equation with an increase in the BMI. Pancreatic size seems to correlate with the actual amount of digested food. The increase in BMI is only an indicator of food intake. DISCUSSION: Pancreatic size might therefore be useful for the assessment of normalization of the eating pattern. Future research is necessary to investigate the impairment of pancreatic function resulting from dystrophy, the impact of possible pancreatic malfunction on the course of eating disorders, and the regulatory mechanisms responsible for the change of pancreatic size.

Accuracy of 13C-urea breath test in clinical use for diagnosis of Helicobacter pylori infection.

UNLABELLED: The 13C-urea breath test (UBT) is a noninvasive test for diagnosis of Helicobacter pylori infection of gastric mucosa. The aim of this prospective study was to assess the accuracy of a simple UBT in clinical routine use. METHODS: The study population comprised of 100 patients (49 f, 51 m) requiring diagnostic upper GI endoscopy. One biopsy specimen was taken from the gastric antrum, body and fundus, respectively, for standard histological examination and one additional specimen from each location was transformed into transport medium for cultivation of H. pylori. After vaccination of the culture plates the biopsies were tested for urease activity (UAT). After recovery from endoscopy the patients had to pass an one liter endexspiratory breath sample before and 15 min after drinking 200 ml orange juice, pH 3.6, containing 75 mg of 13C-urea. 13CO2 was measured in the breath samples using isotope-selective nondispersive infrared spectrometry. RESULTS: Defining gold standard groups with all biopsy tests (from antrum and corpus) positive or negative the 13CO2 delta over baseline (DOB) cut-off level of UBT was set at 6.5/1000 in order to best discriminate positive from negative patients (ROC analysis). UBT was positive in 37% of all subjects. Taken UAT and histological examination together (positive when both tests were positive) UBT displayed a sensitivity of 92%, a specificity of 94%, a positive predictive value of 89%, and a negative predictive value of 94%. When including the results of culture sensitivity and negative predictive value reached almost 100%. The mean of the 13CO2-DOB values from H. pylori-positive duodenal or gastric ulcer patients did not differ from controls (H. pylori-positive patients without lesions). The 13CO2-DOB values of the ulcer group were correlated significantly with the active inflammatory component of gastritis in antrum, corpus, and fundus. CONCLUSION: UBT with this setup detects H. pylori infection in clinical routine use with high accuracy. The increase of exhaled 13CO2 does not predict ulcer disease but reflects the degree of active inflammation of gastric mucosa.

Mediators of exocrine pancreatic secretion induced by intraduodenal application of bile and taurodeoxycholate in man.

The aim of the study was to investigate whether cholecystokinin, neurotensin, and cholinergic mechanisms act as mediators of bile salt-stimulated exocrine pancreatic secretion. Ten fasting healthy subjects provided with a double-lumen tube received 2, 4, and 6 g cattle bile and 200, 400, and 600 mg Na-taurodeoxycholate (TDC) into the duodenum at 65-min intervals, respectively. The application of TDC was repeated in another 10 subjects after intravenous bolus injection of 2.5 micrograms/kg b.w. atropine followed by continuous infusion of 5 micrograms/kg.h. Secretions of volume, bicarbonate, trypsin, and lipase were determined in 10-min fractions of duodenal juice. Plasma samples were analysed for cholecystokinin-like immunoreactivity (CCK-LI) and neurotensin with radioimmunoassays. Volume, bicarbonate, trypsin, and lipase secretion rates were significantly increased by 4 g and 6 g bile and by all doses of TDC. Incremental volume and bicarbonate output was dose-dependently enhanced by bile and TDC, and trypsin and lipase output by bile. Atropine significantly decreased the baseline values and all responses to TDC. Plasma concentrations and integrated CCK-LI and neurotensin significantly increased after 4 and 6 g bile and after 400 and 600 mg TDC. Atropine did not significantly influence peptide release. It is concluded that both hydrokinetic and ecbolic pancreatic secretion stimulated by intraduodenal bile and TDC are dependent on a cholinergic tone. CCK and probably also neurotensin act as further mediators of the ecbolic effect.

Exocrine pancreatic secretion and plasma levels of cholecystokinin, pancreatic polypeptide, and somatostatin after single and combined intraduodenal application of different bile salts in man.

Bile salts are intraduodenal stimulants of basal pancreatic secretion. This study aims to show whether the three main bile salts of human bile differ in their action on pancreatic secretion, and whether they enhance or inhibit each other after combined use. Furthermore, the effect on gastroenteropancreatic peptide release is evaluated. Twelve subjects were provided with a gastroduodenal double-lumen tube. Equimolar doses (0.6 mmol) of taurocholate (322 mg), taurodeoxycholate (313 mg), and a combination of both stimuli were given intraduodenally. Another 12 subjects received taurochenodeoxycholate (313 mg) instead of taurocholate. Volume, bicarbonate, trypsin, and lipase were determined in duodenal aspirates. Cholecystokinin, pancreatic polypeptide, and somatostatin were measured radioimmunologically in plasma samples. All bile salts and combinations exerted a significant hydrokinetic and ecbolic effect. The hydrokinetic response of the combined stimuli was significantly higher as compared with taurocholate and taurochenodeoxycholate, respectively. As far as concerns the ecbolic response, the difference was significant only for trypsin output as compared with taurochenodeoxycholate. Plasma cholecystokinin rose significantly only after the combined stimuli. Pancreatic polypeptide and somatostatin increased significantly after all stimuli, except pancreatic polypeptide after taurocholate. Combined use enhances the hydrokinetic and ecbolic effects of single bile salts. Cholecystokinin may, hereby, be involved as a mediator of the ecbolic effect. Pancreatic polypeptide release indicates cholinergic mechanisms as further mediators. As demonstrated by somatostatin release, counter-regulatory mechanisms are also triggered by intraduodenal bile salts.

Suppression of vagus-mediated pancreatic polypeptide release by the mu-opiate receptor agonist loperamide in man.

1. Morphine suppresses the release of pancreatic polypeptide, a hormone under vagal cholinergic control. The intention of the study was to detect whether the mu-opiate receptor agonist loperamide is also able to inhibit pancreatic polypeptide release, and to define its site of action. 2. In groups of healthy subjects (n = 6 each) stimulation of pancreatic polypeptide was assessed in five different tests: (i) insulin-hypoglycaemia; (ii) modified sham feeding; (iii) intravenous infusion of the cholecystokinin analogue ceruletide; (iv) injection of corticotropin releasing hormone; (v) infusion of the muscarinic acetylcholine agonist bethanechol. All tests were performed after oral application of either a placebo or loperamide (16 mg), tests (ii) and (iii) were repeated with loperamide in smaller doses (2 and 6 mg), with loperamide plus naloxone, with naloxone alone, and with infusion of atropine. Plasma concentrations of pancreatic polypeptide were measured radioimmunologically. 3. Release of pancreatic polypeptide in test (i) to (iv) was completely blocked by 16 mg loperamide, whereas bethanechol-stimulated release (test 5) was not influenced. Tests (ii) and (iii) showed that the inhibition was dose-dependent and could be attenuated by naloxone. The inhibitory effect of loperamide was comparable with that of atropine. 4. We conclude that loperamide causes a dose-dependent inhibition of pancreatic polypeptide release mediated by vagal-cholinergic pathways, but does not have an atropine-like peripheral action.

Effect of intraduodenal taurodeoxycholate and L-phenylalanine on pancreatic secretion and on gastroenteropancreatic peptide release in man.

Intraduodenally applied bile salts and essential amino acids are known to stimulate exocrine pancreatic secretion. There are contradictory reports, however, about an interaction of both stimuli with respect to pancreatic function. The intention of the study was to compare the effects of equimolar amounts of taurodeoxycholate and L-phenylalanine used singularly and combined on pancreatic secretion and on gastroenteropancreatic peptide release. In 12 healthy subjects, 0.8 mmol of Na-taurodeoxycholate (410 mg) and L-phenylalanine (130 mg) were separately and combined applied into the duodenum in a randomized order. Volume, bicarbonate, trypsin, lipase, and amylase secretion as well as cholecystokinin, pancreatic polypeptide, and somatostatin plasma levels were measured. Volume and bicarbonate secretion was significantly enhanced by taurodeoxycholate. The effect was stronger compared to L-phenylalanine. The increase of enzyme secretion was comparable. After combined application, the ecbolic effect was insignificantly smaller, whereas the hydrokinetic effect was between those of the single stimuli. Plasma levels of cholecystokinin, pancreatic polypeptide, and somatostatin rose concomitantly with the pancreatic response. On an equimolar basis taurodeoxycholate results in a stronger hydrokinetic effect than L-phenylalanine. Their ecbolic effects, however, are comparable. In addition to cholinergic mechanisms, as indicated by the PP release observed, cholecystokinin may also act as a mediator. In combined application, the stimuli interfere with each other. Somatostatin and pancreatic polypeptide are not responsible for this mutual inhibition.

[Gastrointestinal involvement in progressive systemic scleroderma]. / Gastrointestinale Beteiligung bei progressiv-systemischer Sklerodermie (PSS).

The complained gastrointestinal symptoms in PSS are probably caused by several complex disturbances like intestinal transit disturbances (ITD), bacterial overgrowth of the small intestine caused malabsorption of bile acids and altered kinetics of intestinal hormones. 25 patients with PSS and eleven healthy controls were tested for the existence of ITD by use of the metal-detector test (MDT). Twelve patients were also tested for a malabsorption of primary bile acids by radioimmunological measurement of clolylglycine serum levels before and after a meal. In addition serum concentrations of gastrin (nine patients) and plasma concentrations of cholecystokinin (CCK) (eight patients) and motilin (eleven patients) were measured by radioimmunoassay pre- and postprandial. Interdigestive gastric emptying was accelerated in patients with PSS (53 +/- 3 min. vs. 73 +/- 7 min.; p<0.01). Small intestinal transit times were similar in both groups (115 +/- 17 min. vs. 121 +/- 13 min.). Colonic transit in patients with PSS was significant prolonged (63 +/- 6 h vs. 39 +/- 5 h; p<0.05). There were no significant differences between the two groups concerning the pre- and postprandial levels of cholylglycin. Basic and postprandial levels of gastrin, CCK and motilin were higher in the PSS group. In contrast to scintigraphic studies using semisolid meals gastric emptying of the copper pellet in PSS was accelerated. A general malabsorption of primary bile acids was not found. Prolonged colonic transit times correlate well with frequently complained obstipation. Gastric hypacidity could be the reason of elevated gastrin levels. The high motilin-levels in PSS could be due to a lack of the feed-back inhibition as a result of diminished phase-III activity of the interdigestive migrating motor complex. The elevation of CCK-levels could reflect compensation of neurogenic or myogenic disturbances of gallbladder contraction.

Gastrointestinal intramural hematoma, a complication of endoscopic injection methods for bleeding peptic ulcers: a case series.

In a prospective study, all patients with peptic ulcer bleeding were documented between February 1984 and April 1992. A total of 227 patients were treated by local injection of epinephrine followed by laser application and injection of polidocanol or fibrin tissue adhesive. In five of these patients, intramural hematomas developing at the former bleeding site one to three days after endoscopic treatment were observed. The presenting symptoms were abdominal pain, nausea, and vomiting. The diagnosis was established by endoscopy, abdominal ultrasound, computed tomography, or laparotomy. In four of our five patients, the bleeding site and hematoma were located in the duodenum. All patients suffered from severe underlying diseases, and showed a clear disturbance of coagulation parameters. In three patients, acute pancreatitis occurred concurrently with the hematoma, probably due to obstruction of the papilla of Vater or compression of the pancreas caused by the hematoma.

In man the mu-opiate agonist loperamide specifically inhibits ACTH secretion induced by the cholecystokinin-like peptide ceruletide.

Ceruletide, a cholecystokinin-8-like peptide, was recently reported to stimulate ACTH secretion in man. The aim of this study was to investigate the effect of the mu-opiate agonist, loperamide, and the opiate antagonist, naloxone, on ceruletide-induced ACTH secretion in man. In 6 normal subjects, basal ACTH and cortisol plasma levels were significantly suppressed 3 h after loperamide administration (16 mg, orally) from 5 +/- 0 to 2 +/- 0 pmol/l and from 356 +/- 44 to 154 +/- 16 nmol/l. After stimulation with 8 ng ceruletide/kg body weight/min over a period of 5 min, the maximum ACTH levels (at 7.5 min) were significantly reduced by loperamide from 26 +/- 7 to 6 +/- 1 pmol/l and the maximum cortisol levels (at 30 min) were significantly reduced from 676 +/- 47 to 392 +/- 58 nmol/l. Furthermore, the ACTH peak (delta = 7.5 min) was significantly blunted by loperamide from 21 +/- 7 to 5 +/- 1 pmol/l and the integrated area under the curve from 0 to 120 min (delta AUC) of ACTH was significantly reduced from 40 +/- 11 to 14 +/- 4 pmol x 120 min/l. The cortisol peak (delta = 30 min) and the AUC of cortisol were not significantly diminished. The suppressive effect of loperamide on basal and ceruletide-induced ACTH and cortisol secretion was completely reversed by the administration of 0.8 mg naloxone, 20 min before and during infusion of ceruletide. The administration of naloxone itself had no significant effect on ACTH or cortisol levels. In conclusion, ACTH is released by peripherally administered ceruletide within a short period.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of intraduodenal bile and taurodeoxycholate on exocrine pancreatic secretion and on plasma levels of vasoactive intestinal polypeptide and somatostatin in man.

Intraduodenal (i.d.) application of bile or Na-taurodeoxycholate (TDC) dose dependently enhances basal exocrine pancreatic secretion. The hydrokinetic effect is mediated at least in part by secretin. This study should show, whether vasoactive intestinal polypeptide (VIP), a partial agonist of secretin, may also be involved in the mediation of the hydrokinetic effect. Furthermore, plasma concentrations of somatostatin-like immunoreactivity (SLI) were measured in order to check whether this counterregulating hormone is also released by bile and TDC. Twenty investigations were carried out on 10 fasting healthy volunteers provided with a double-lumen Dreiling tube. Bile and TDC were intraduodenally applied in doses of 2-6 g and 200-600 mg, respectively, at 65-min intervals. Plasma samples were withdrawn at defined intervals for radioimmunological determination of VIP and SLI. Duodenal juice was collected in 10-min fractions and analyzed for volume, pH, bicarbonate, lipase, trypsin, and amylase. I.d. application of bile or TDC dose dependently stimulated hydrokinetic and ecbolic pancreatic secretion. Bile exerted a slightly stronger effect than TDC. Pancreatic response was simultaneously accompanied by a significant increase of plasma VIP and SLI concentrations. The effect of bile on integrated plasma VIP and SLI concentrations seems to be dose dependent; the effect of TDC on integrated SLI, too. For the increase of integrated plasma VIP concentrations after TDC no dose-response relation could be established. We conclude that VIP may be a further mediator of bile-induced volume and bicarbonate secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

The mediators of bile action on the exocrine pancreas.

Under basal conditions, bile and bile salts applied intraduodenally influence plasma levels of several gastroenteropancreatic peptides. Besides those with stimulatory effects on exocrine pancreatic secretion, others with inhibitory or no effects are released as well. Furthermore, cholinergic and peptidergic neural mechanisms may also be activated. Secretin seems to be the most important mediator of bile- or bile salt-induced water and bicarbonate secretion. In addition, VIP released from peptidergic nerve endings in the pancreas may also be involved in the mediation of the hydrokinetic effect. With regard to water and bicarbonate secretion, cholinergic mechanisms probably are of minor importance. Cholinergic mechanisms, however, seem to be the most important mediator of bile- or bile salt-induced pancreatic enzyme secretion. CCK may act as an additional mediator of the ecbolic effect. This statement, however, is based on few results only and has to be confirmed by further studies. Gastroenteropancreatic peptides with an inhibitory action on the exocrine pancreas were also released by intraduodenal bile or bile salts. Somatostatin is released in physiologically relevant amounts to bring about a counter-regulation. Plasma PP levels are also enhanced by bile and bile salts. The amounts of PP released, however, are below those observed postprandially. In contrast to their stimulatory action on basal pancreatic secretion, bile and bile salts have no or even an inhibitory effect on pancreatic secretion stimulated by intraluminal nutrients. Accordingly, the release of gastroenteropancreatic peptides is not influenced (for example, secretin) or even reduced (for example, CCK) when bile or bile salts are added to intraluminal nutrients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Enzyme liberation and activation of the kallikrein-kinin system in experimental pancreatitis. Studies of portal vein blood, pancreatic lymph and peritoneal effusion]. / Enzymfreisetzung und Aktivierung der Kallikrein-Kinin-Systeme bei experimenteller Pankreatitis. Untersuchungen in Pfortaderblut, Pankreaslymphe und Peritonealexsudat.

The clinical course of acute pancreatitis is strongly influenced by secondary cardiac, pulmonary and renal damage. The aim of the present study was to gather information about the compartment promoting the systemic damage. Therefore the activity of lipase, phospholipase A and plasma pro-kallikrein and the concentration of tissue kallikrein and kininogen were measured in portal venous blood, pancreatic lymph and peritoneal exudate. Anaesthetized pigs were subjected to fluid resuscitation to keep systemic haemodynamic parameters constant. The pancreas was isolated in situ. The pigs were randomly assigned to a control group (n = 9) or one of the two pancreatitis groups (n = 10 each). Pancreatitis was induced by i.a. infusion of free fatty acid (FFS) or retrograde infusion of 5% sodium taurocholate intraductally (NaT). In both pancreatitis groups the activity of lipase and phospholipase A increased. The most pronounced changes were seen in the peritoneal exudate (phospholipase A activity 40 min after induction: control 10.0 U/l, NaT 72.2 U/l). In both pancreatitis groups there was evidence for activation of the tissue kallikrein kinin system in the form of an increase in the kallikrein concentration and a decrease in the kininogen concentration. Again the changes were most pronounced in the peritoneal exudate (tissue kallikrein 40 min after induction: control 14.7 ng/ml, NaT 452 ng/ml).

Hemodynamic effects following intraperitoneal infusion of pancreatic ascites fluid.

Severe necrotizing pancreatitis is accompanied by release of hemorrhagic ascites fluid (HAF), which is thought to be related to the occurrence and frequency of cardiocirculatory and pulmonary failure as a consequence of acute pancreatitis. The purpose of this study was to evaluate the role of HAF due to these systemic complications. Experiments were performed in 25 pigs (mean b.wt. 22 +/- 1 kg) under general anesthesia and mechanical ventilation. The animals received 50 ml/kg b.wt. i.p. of either physiologic saline solution (control CO, n = 9) or hemorrhagic ascites fluid (HAF, n = 16). HAF was obtained from 16 pigs with pancreatitis induced by intraductal infusion of bile salt. Eight animals in the HAF group were pretreated with indomethacin (10 mg/kg i.v. INDO/HAF). All animals were followed up for 6 h. Mean arterial pressure, cardiac output, and stroke volume fell significantly in the HAF (-25%, -27%, -27%) and in the INDO/HAF groups (-24%, -20%, -17%) as compared with controls (-6%, -6%, -6%). Also, left ventricular end-diastolic pressure (LVEDP) decreased by 52% and 48% in both HAF recipient groups, whereas LVEDP was unchanged in the control group. Myocardial contractility (Vmax) remained unaltered in all experimental groups. No significant differences in gas exchange and lung dry/wet weight ratio were observed. Lipase and PGI2 of the unpretreated HAF group rised to 203% and 198% in arterial blood at 6 h compared with unaltered levels in the control group. No increase of prostanoid concentrations was detected in the indomethacin-pretreated group, whereas lipase increase by a comparable extent as in the HAF group. We conclude that the early consequences of HAF are mainly characterized by systemic hypotension due to hypovolemia.