Poul Erik Mortensen

Truncated GLP-1 (proglucagon 78–107-amide) inhibits gastric and pancreatic functions in man

We studied the effect of intravenous infusion of synthetic truncated GLP-1 (proglucagon 78–107-amide) on fasting and postprandial gastric acid secretion, gastric emptying, and pancreatic secretion of trypsin and lipase in eight normal volunteers using marker dilution and aspiration technique. The infusion resulted in a plasma concentration of 110±14 pmol/liter (mean±SEM). Truncated GLP-1 significantly inhibited postprandial acid secretion by 43±11%, in spite of unchanged plasma gastrin concentration. Gastric emptying rate decreased significantly; 50% emptying time increased from 16±2 min to 30±5 min. Postprandial trypsin and lipase outputs were significantly inhibited by 47±17% and 40±9%, during truncated GLP-1 infusion. Pancreatic enzyme output was linearly correlated to gastric emptying, and truncated GLP-1 did not affect this relationship, suggesting that the effect on pancreatic secretion was secondary to the effect on gastric emptying. Postprandial insulin and glucagon concentrations were similar with and without truncated GLP-1 infusion in spite of significantly lower blood glucose levels (5.2 ±0.2 versus 3.7±0.3), indicating that GLP-1 stimulated insulin secretion and inhibited glucagon secretion. In conclusion, our results suggest that truncated GLP-1 act as a physiological inhibitor of gastric and pancreatic functions in man.

Oxyntomodulin from distal gut. Role in regulation of gastric and pancreatic functions.

We studied the effects of intravenous infusion of synthetic oxyntomodulin (proglucagon 33–69), a potential hormone from the ileal mucosa, on fasting and postprandial gastric acid secretion, gastric emptying, gastroduodenal motility, and pancreatic secretion of trypsin and lipase measured simultaneously in six normal volunteers using multilumen tubes for infusion of markers, manometry, and aspiration of gastric and duodenal contents. The infusion resulted in plasma concentrations of 203±21 pmollliter (mean±sem) of oxyntomodulin, regarded as high but not unphysiological concentrations of the peptide. Oxyntomodulin almost abolished basal acid secretion and inhibited postprandial acid secretion by 35±10%. Gastric emptying decreased significantly; the time for 50% to leave the stomach increased from 17.3±2.2 min to 34.7±8.0 min. The postprandial gastroduodenal motility was massively inhibited by oxyntomodulin. Postprandial trypsin and lipase output was significantly inhibited by 56±12% and 42±11%, respectively, during oxyntomodulin infusion. However, pancreatic enzyme output was linearly related to gastric emptying and oxyntomodulin did not influence this relationship, suggesting that oxyntomodulins effect was due to its effect on gastric emptying. Oxyntomodulin seems to play an important role in the small intestinal inhibitory control of gastropancreatic functions.

Oxyntomodulin: a potential hormone from the distal gut. Pharmacokinetics and effects on gastric acid and insulin secretion in man

Abstract Synthetic oxyntomodulin, a predicted product of the glucagon gene, which is produced in the human lower intestinal mucosa, was infused in doses of 100 and 400 ng kg‐1 h‐1 into six volunteers to study its pharmacokinetics and effects on pentagastrin‐stimulated gastric acid secretion (100 ng kg‐1 h‐1). The concentration of oxyntomodulin in plasma measured with a cross‐reacting glucagon assay increased from 37 ± 5 to 106 ± 17 and 301 ± 40 pmol l‐1, respectively. The metabolic clearance rate was 5·2 ± 0·7 ml kg‐1 min‐1 and the half‐life in plasma was 12 ± 1 min. Oxyntomodulin reduced the pentagastrin‐stimulated acid secretion by 20 ± 9% during the low‐rate infusion (P < 0·05) and by 76 ± 10% during the high‐rate infusion (P < 0·05). In accordance with the homology with glucagon, there was a small, significant rise in plasma concentrations of insulin and insulin C‐peptide during oxyntomodulin infusion. Oxyntomodulin may therefore be included among the potential incretins and enterogastrones in man.

The effect of the cholecystokinin receptor antagonist MK-329 on meal-stimulated pancreaticobiliary output in humans

To determine the physiological role of circulating cholecystokinin (CCK), the effect of the CCK receptor antagonist MK-329 on upper digestive processes was investigated in six normal volunteers after a mixed meal. In a double-blind, two-period, randomized crossover design, the subjects received either 10 mg MK-329 or placebo orally 3 hours 15 minutes before the meal, which contained 51CrCl3 as food marker. A five-lumen tube with the tip in the distal duodenum allowed continuous marker infusion (57Co-B12) and duodenal aspiration as well as recordings of antral and duodenal motility patterns via three pressure sensors. Postprandially, MK-329 caused a significant reduction of 30%-60% (P less than 0.05) in pancreatic trypsin output during the initial three 15-minute periods; thereafter, the output was virtually the same than after placebo. Thus, the integrated enzyme response was only reduced by 15% (NS) during the 3-hour period beginning 15 minutes after the meal. In contrast, gallbladder contraction, determined by total bile acid excretion, was inhibited by 77% (P less than 0.05), indicating a crucial role of CCK in regulating gallbladder motility. Except for the initial 30 minutes postprandially, MK-329 also induced a significant reduction in duodenal pH with mean values ranging from 3.5 +/- 0.2 to 4.1 +/- 0.3 compared with 4.5 +/- 0.3 to 5.0 +/- 0.4 after placebo (P less than 0.05), probably because of lowered secretion of pancreatic bicarbonate. Gastric emptying rate was significantly accelerated by MK-329 during the initial 75 minutes after the meal, but the time for 50% emptying did not differ from placebo [127.5 +/- 7.7 vs. 140.0 +/- 9.0 minutes (NS)]. No changes were observed in the motility pattern of the proximal duodenum after feeding. Whereas MK-329 only caused a slight increase of the basal plasma CCK concentrations, the postprandial levels were markedly enhanced. Peak concentrations were 10.0 +/- 1.3 vs. 4.0 +/- 0.5 pmol/L after placebo (P less than 0.001), and the integrated response exceeded the control value by 175% (P less than 0.01). The results suggest that circulating CCK is not an essential mediator of the postprandial pancreatic enzyme secretion in humans, whereas it plays a critical role in gallbladder emptying.

The inflammatory cytokine response after autotransfusion of shed mediastinal blood

Background: The inflammatory response in patients undergoing cardiac surgery with cardiopulmonary bypass is well known and increased levels of inflammatory cytokines have been shown. High levels of cytokines have been reported in blood drained from the surgical field. The present study aimed to elucidate whether autotransfusion of shed mediastinal blood in itself causes increased cytokine levels in coronary artery bypass graft (CABG) patients.

A randomized study on hemorrhoidectomy combined with anal dilatation

Forty patients with third-degree hemorrhoids were randomized in two groups. Seventeen patients had a Milligan hemorrhoidectomy combined with anal dilatation and 23 had hemorrhoidectomy only. Anal manometry was carried out preoperatively at three, six, and 12 months postoperatively. Maximum resting pressure decreased significantly in both groups after surgery, although a small increase in maximum resting pressure was noticed after six months. A significant decrease in anal pressure was measured in both groups after one year. After one year, three patients in the dilation group had minor degrees of incontinence compared to none in the nondilated group. In both groups three patients complained of recurrent symptoms of hemorrhoids. It is concluded that the combination of hemorrhoidectomy and anal dilatation does not improve cure rate compared to hemorrhoidectomy alone, but may increase the risk of continence disturbances.

Autotransfusion after coronary artery bypass grafting halves the number of patients needing blood transfusion

BACKGROUND Several randomized studies about autotransfusion of shed mediastinal blood in patients undergoing coronary artery bypass grafting have resulted in divergent findings concerning reduction of the need for homologous blood transfusions. Most of these studies used less strict criteria for homologous blood transfusion than applied in daily clinical practice. METHODS A prospective, randomized, controlled study involving 120 patients having elective, uncomplicated coronary artery bypass grafting was performed. The autotransfusion group received transfusion of shed mediastinal blood for 18 hours. Criteria for homologous blood transfusion were hemoglobin concentration less than 5.0 mmol/L in the intensive care unit and less than 5.5 mmol/L during the rest of the hospital stay. RESULTS Twenty-eight percent of patients in the autotransfusion group received homologous blood transfusion versus 55% in the control group (p = 0.007). Ninety-five percent of the shed mediastinal blood was transfused. In the autotransfusion group, a total of 26 units of homologous blood was used versus 78 units in the control group (p < 0.001). CONCLUSIONS Autotransfusion of shed mediastinal blood in patients undergoing elective, uncomplicated coronary artery bypass grafting halves the number of patients needing homologous blood and reduces the amount of homologous blood given.

Cardiac enzymes and autotransfusion of shed mediastinal blood after myocardial revascularization

BACKGROUND Autotransfusion of shed mediastinal blood reduces blood requirement after coronary artery bypass grafting. Recently, two nonrandomized trials indicated that autotransfusion elevates the levels of cardiac enzymes after cardiac operations. METHODS Prospective, randomized controlled studies involving 120 patients (study A) and 15 patients (study B) having elective uncomplicated coronary artery bypass grafting were performed. Autotransfusion of shed mediastinal blood was performed for 18 hours in the patients allocated to autotransfusion. Serum levels of cardiac enzymes were measured. In study B cardiac enzyme levels in shed mediastinal blood and circulating blood were measured 1 hour postoperatively. RESULTS Cardiac enzyme levels were significantly elevated in the patients receiving autotransfusion. In patients with a perioperative myocardial infarction. The level of creatine kinase-MB was much higher than in the autotransfused patients without myocardial infarction. The level of cardiac enzymes was higher in shed mediastinal blood compared with circulating blood. CONCLUSIONS Postoperative autotransfusion of shed mediastinal blood causes elevation of cardiac enzyme levels after coronary artery bypass grafting.

Impact of autotransfusion after coronary artery bypass grafting on oxygen transport.

Background: Autotransfusion of shed mediastinal blood after coronary artery bypass grafting (CABG) has been shown to reduce the requirement for allogeneic blood. We have previously demonstrated in non‐randomized studies that the oxygen capacity of shed mediastinal blood is similar to the patients circulating blood and better than stored allogeneic blood. Therefore, we wanted to examine the influence of autotransfusion of shed mediastinal blood on oxygen transport capacity in patients undergoing CABG.

Effect of Somatostatin on 133Xe Clearance from Colonic Mucosa before and after Local Nervous Blockade in Unanaesthetized Man

The effect of intravenous somatostatin bolus on mucosal and submucosal blood flow in six patients with colostomies was studied with the local 133Xe clearance technique. Mucosal and submucosal blood flow decreased by 28% after somatostatin injection. After induction of local nervous blockade by infiltrating the labelled area of the mucosal membrane with lidocaine the reduction in blood flow caused by somatostatin was abolished. These observations suggest that the vasoconstrictor effect of somatostatin is mediated by neurogenic mechanisms.