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Biomedical subjects

A Bergan

Publications and source records attributed to A Bergan.

108 records · Page 6Linked to original sources

The synthesis and excretion of non-erythroid bilirubin in the dog.

Between 10 and 20% of the bilirubin excreted in the bile is not derived from the breakdown of hemoglobin. When delta-aminolevulinic acid is given as a bilirubin precursor, 99% of the bilirubin formed is of this non-erythroid variety. The non-erythroid bilirubin has been supposed to be synthetized exclusively in the liver. Sequential samples of arterial, portal and liver vein blood, as well as of bile and thoracic duct lymph, were analyzed for bilirubin and non-bilirubin radioactivity following the injection of labeled delta-aminolevulinic acid in dogs. Radioactive bilirubin appeared in blood before it could be demonstrated in bile or lymph. The concentration differences between aortic, portal and liver vein blood displayed a considerable extrahepatic non-erythroid bilirubin synthesis. Most non-erythroid bilirubin synthetized in the liver is excreted directly into the biliary canaliculi.

Animals↗

Operative results in portal hypertension with bleeding oesophageal varices.

During a 15-year period 81 patients with bleeding oesophageal varices were admitted to our department. Nearly 90% had liver cirrhosis, 21% were alcoholics. 67 portosystemic shunts were performed in 63 patients, in 11 of these as an emergency shunt. Overall operative mortality in electively shunted patients was 10.7%. Even in those with the most severe liver insufficiency (Child's group C) operative mortality was below 20%. Operative mortality in elective cases was closely correlated to peroperative bleeding. Only 1 of 45 patients needing less than 10 units of blood peroperatively died, while mortality in the multitransfused group was 45.5%. Both patients surviving urgent shunt surgery were operated on early, i.e. before they had received 5 units of blood.

Adolescent↗

Myocardial blood flow in the diving seal.

Grey seals exhibit a marked drop in heart rate, a slight decrease in ventricular contractility, and an essentially unchanged stroke volume upon diving. In the present study, we have demonstrated that the resulting drop in cardiac output is associated with a 90% reduction of coronary blood flow. Such reduction of myocardial blood flow takes place despite a significant increase in effective coronary driving pressure, and is indicative of a 800% increase in coronary vascular resistance. This means that the circulatory adjustments displayed by the diving seal (i.e. a reduction of the workload on the heart) are so effective that myocardial blood flow can be reduced to 10% of the pre-dive value without loss of cardiac function and blood pressure. It is suggested that even partial simulation of such a circulatory state might be a successful approach in the treatment of ischemic injuries in the heart of man.

Animals↗

Blood volume partition after acute cholestasis in the rat.

A method involving isotope labelling of blood components and then rapid freezing of intact rats, was used for evaluation of the blood content in liver, spleen and gastrointestinal (GI) tract in cholestatic animals. For comparison also another important blood depot, i.e. the lungs were examined. After 4 days of cholestasis the animals were hypovolemic, however, the partition of blood in the liver and GI tract was unchanged or even increased. In contrast the lung blood volume and the erythrocyte content of the spleen were markedly reduced. Three days later the animals had regained their normal blood volume, but still there was a redistribution of blood from the lungs and spleen to the liver and GI tract. We suggest that during cholestasis the depot function of the splanchnic vessels is disturbed. This might be one factor of importance for development of the hepatorenal syndrome.

Acute Disease↗

Effects of different doses of acetylsalicylic acid on renal function in the dog.

This study was carried out in order to examine the effect of increasing doses of intravenously administered lysine-acetylsalicylic acid (ASA) on renal function in dogs. The first purpose was to examine the acute effects on renal water and solute output. The second purpose was to correlate the para-aminohippuric (PAH) clearance measurements with measurement of renal PAH extraction and renal blood flow (RBF). After 7 mg/kg ASA (20-80 microgram SA/ml plasma) a decrease in sodium excretion was observed in all dogs. With increasing ASA doses, the urine sodium excretion declined to 23% of the control period excretion. Tubular reabsorption of free water increased 10%. A significant and dose-related decrease in PAH clearance was observed in all dogs, from 108.7 ml/kg ASA to 58.8 ml/min after 200 mg/kg ASA. The creatine clearance was unchanged. PAH extraction fell in all dogs, RBF (measured by flowmeter decreased 21% at the highest plasma SA levels, as compared with 46% decrease in PAH clearance. ASA seems to inhibit tubular transport of PAH. Inhibition of prostaglandin synthesis by ASA offers one explanation of the effects of RBF and sodium excretion.

Animals↗

Effects of different doses of chlorpromazine on renal function in the dog.

This study was carried out to examine the effects of low 'alpha-blocking' and higher 'membrane-stabilizing' doses of chlorpromazine (CPZ) on renal function. CPZ was given at slow infusion rate either intravenously or into the left renal artery at three levels (0.5-1.0, 3-8, and 10-15 mg/kg) to 10 anesthetized dogs. An increase in plasma hemoglobin sometimes occurred within few minutes after infusion of more than 10 mg/kg CPZ, probably due to a hemolytic effect of such high doses. Systemic infusion of 0.5-1 mg/kg CPZ caused an increase in urine volume, sodium excretion, and renal plasma flow, and a decrease in filtration fraction and free water clearance was demonstrated in all dogs. At higher CPZ doses renal plasma flow increased further, whereas urine volume and electrolyte excretion were of the same order at all dose levels. A 21% decrease in tubular maximum para-aminohippurate transport (Tm(PAH)) was observed at the highest CPZ doses. After unilateral renal intra-arterial CPZ infusion the percentage change in urine volume, urinary sodium excretion, and Tm(PAH) were of the same order on the infused side as on the contralateral side. Even though the results at all dose levels can be explained by an 'alpha-blocking' effect of CPZ, possible membrane-stabilizine effects of CPZ cannot be excluded.

Animals↗

Transport and conjugation of 14C-bilirubin during acute and chronic cholestasis in the cholecystectomized dog.

The role of the lymphatics in the regurgitation of bilirubin during acute and chronic extrahepatic cholestasis in the dog was studied after intravenous injection of 14C-bilirubin. In acute cholestasis the injected labelled bilirubin was rapidly removed from plasma and reappeared in thoracic duct lymph as labelled bilirubin conjugates. No labelled conjugates were at any time demonstrated in plasma. This is most easily explained as a result of a bilio-lymphatic regurgitation. In chronic cholestasis the labelled bilirubin conjugates were delivered back into the blood, and no specific transport function of the lymph was found. Our results indicate a change in liver cell secretory direction in long-standing cholestasis.

Acute Disease↗

Plasma concentration of lipoprotein-X (LP-X) in experimental bile duct obstruction.

Sequential quantitative determinations of lipoprotein-X (LP-X), measurements of plasma lipids, initial rate of cholesterol esterification, and liver function tests were performed after experimental cholestasis in 6 dogs. In 3 animals ligation and transsection of the common bile duct were combined with cholecystectomy. In 2 other dogs a similar operation, but without removal of the gallbladder, was carried out. In the bile-duct-obstructed and cholecystectomized dogs, LP-X appeared 11-21 hours after operation, and in dogs with preserved gallbladder 32 hours after operation. During the observation periods (6-41 days), the LP-X levels were much higher in the cholecystectomized dogs than in the ones with preserved gallbladders. In most of the bile-duct-obstructed dogs the curves of LP-X concentrations in plasma were bi-phasic. The first peak after 1 to 5 days was followed by a fall, and 10 to 14 days after operation another rise was observed. Concomitant with the changes in the level of LP-X, fluctuations in the levels of phospholipids and free cholesterol occurred. An inverse relationship between LP-X and the activity of lechithin: cholesterol acyltransferase was found.

Acyltransferases↗

Conjugation of non-erythroid bilirubin in chronic experimental cholestasis in the dog.

The dynamics of conjugation of 14C-bilirubin injected intravenously during cholestasis is known from studies in rats and dogs. No studies have been performed concerning the conjugation of non-erythroid bilirbuin (NEB), i.e. the 10-20% of bilirubin synthesized from tissue haemes, mainly in the liver. This study reports the results of experiments in four dogs subjected to extra-hepatic cholestasis of 7-14 days' duration. delta-Aminolevulinic acid-5-C14HCi was injected intravenously as a NEB precursor. The appearances of unconjugated and conjugated labelled NEB as well as of the different azopigments were followed in systemic blood, liver vein blood, and thoracic duct lymph. The first NEB to appear was unconjugated; maximal concentration of unconjugated NEB in peripheral and liver vein blood was reached within one hour. The amount of conjugated NEB in both vascular compartments increased for two to three hours, after which time the degree of conjugation stabilized. The degree of conjugation was higher in liver vein than in peripheral blood for the first two hours. The same azopigments of NEB were found as for injected 14C-bilirubin. The a0 azopigment (azobilirubin) was present in higher amounts in peripheral than in liver vein blood, all the other azopigments were present in higher amounts in liver vein blood.

Aminolevulinic Acid↗

The role of the liver lymphatics in the transport of non-erythroid bilirubin during different stages of experimental cholestasis.

The role of the liver lymphatics in the regurgitation of bilirubin during the different stages of cholestasis has been a matter of debate. Earlier studies have shown that 14C-bilirubin injected intravenously one hour after induction of cholestasis was rapidly and completely cleared from the blood and appeared in the thoracic duct lymph in high concentration. During chronic cholestasis the injected 14C-bilirubin was delivered directly back to the blood after conjugation in the liver. The aim of the present study was to investigate the role of the lymphatics in the transport of non-erythroid bilirubin (NEB), a metabolic product of certain tissue haemes, produced mainly in the liver. The study was carried out in dogs. Five dogs were studied in the first hours following bile duct obstruction, and five others after at least one week of cholestasis. 14C-delta-aminolevulinic acid was given as a NEB precursor. In contrast to the results obtained with 14C-bilirubin injection, evidence for a delivery of conjugated labelled NEB directly to the blood during acute cholestasis was found. The concentration curves for NEB and non-NEB radioactivity in the thoracic duct lymph indicated the presence of a secondary biliolymphatic regurgitation. In chronic cholestasis no evidence for such a biliolymphatic regurgitation of NEB was found.

Acute Disease↗

Complete biliocolic fistula.

A case of postoperative complete biliocolic fistula is described. The patient had 10 daily voluminous motions of diarrhoea and lost 14 kg in weight in the course of two months. Increased faecal fat excretion was demonstrated. Treatment with oral tetracyclines resulted in cessation of the watery diarrhoea and some weight gain, but steatorrhoea persisted. Closure of the biliocolic fistula with re-established bile flow to the proximal small intestine cured the patient. A discussion of the case based on the present knowledge of bile salt metabolism and bile salt- bacterial interrelationship is presented.

Adult↗

Wash-out of intraparenchymally injected Xenon-133 as a parameter of liver blood flow in the dog.

The method of intraparenchymal injection of xenon-133 for measurement of blood flow was evaluated for use in the liver. Repeated injections in the same liver gave rise to a great range of flow values, pointing to a heterogeneous liver perfusion. The use of single measurements for determination of liver blood flow with this method is not acceptable. Comparison between different livers is only possible when several injections are made and the results are given a statistical characterization. Flow values obtained generally did not correlate well with values determined by other methods. The method therefore seems suitable only for comparative and qualitative studies.

Animals↗

Technical aspects and complications of end-ileostomies.

During a period of 10 years (1980-1990) we constructed or reconstructed 358 end-ileostomies: 224 were primary constructions, 96 were reconstructed by laparotomy, and 38 were local reconstruction. Only 2 ileostomies were primarily located on the left side. The mean length was 5 cm. We had 11.6% reoperations after primary stomy and 7.3% and 7.9% reoperations after reconstruction by laparotomy and local approach, respectively. There were 12.9% and 8.7% reoperations after emergency and elective primary operations, respectively. Closing the lateral gutter or fixation of ileum to the rectus fascia did not influence significantly the number of reoperations. Postoperative discolored stomy did not indicate more dysfunction of the ileostomy. Stenosis of the ileostomy, peristomal fistulas, and peristomal dermatitis were seen in 23 (10.3%), 21 (9.4%), and 18 (8%) of the patients after primary ileostomies, respectively. Patients with Crohn's disease had significantly more of these problems than patients with ulcerative colitis. Only a few patients had retraction of the ileostomy (2.7%), stomal prolapse (1.8%), or parastomal herniation (1.8%). Women had significantly more parastomal herniation than men; otherwise there were no differences between the sexes.

Constriction, Pathologic↗

Changes in pharmacokinetics of cisplatin after hepatic resection in rats.

Adjuvant chemotherapy concomitant with hepatic resection has been considered as treatment of patients with hepatocarcinoma. To examine the influence of a partial hepatectomy on the platinum pharmacokinetics, rats were given a single dose of cisplatin (2 mg/kg) prior to 2/3 hepatic resection or sham operation. The partially hepatectomized rats showed a 44% increase in the AUC between 2-48 hr compared with the sham-operated controls. The terminal plasma half-life from 12-48 hr was 21.1 hr for the partially hepatectomized rats and 14.7 hr for the sham-operated animals. Total platinum concentration in liver tissue was 1.3 times that of plasma 20 min after injection. Although cisplatin is considered to be eliminated mainly via renal excretion, our finding may suggest a role for the liver in the elimination of platinum.

Animals↗