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Biomedical subjects

S Bengmark

Publications and source records attributed to S Bengmark.

At least 37 records · Page 2Linked to original sources

The functional effects of suppression of hypothermia-induced cell swelling in liver preservation by cold storage.

It is known that cellular edema and functional impairment develop during anaerobic cold storage of organs. The extent of both is related to the storage time and the composition of the preservation solution used. We studied hypothermia-induced cell swelling and its effect on liver function after cold storage preservation with either Eurocollins (EC), a number of modified EC solutions in which glucose was replaced by various concentrations of raffinose, or UW solution. After 24 h storage, tissue swelling as determined by total tissue water (TTW) in rat liver tissue slices was most pronounced in slices incubated in Eurocollins, whereas the TTW was only moderately increased in slices stored in modified Eurocollins containing 90 to 120 mM raffinose. In contrast, slices incubated in UW solution had a TTW equal to normal rat liver tissue. Furthermore, intact rabbit livers preserved with Eurocollins had an increase in the whole organ weight, while there was no weight change after preservation with the modified solution containing 120 mM raffinose (M120). In contrast, a pronounced weight loss was observed after preservation with UW solution. After cold storage, the livers were reperfused for 2 h at 38 degrees C in an isolated perfusion circuit (IPL) with an acellular perfusate. Bile flow was significantly greater in livers preserved in M120 than in those preserved with the conventional Eurocollins. However, the bile flow in the livers stored in M120 was inferior to that in the livers preserved with UW solution, which in turn was equal to that in control livers. The release of alanine-aspartate-aminotransferase into the perfusate was higher in livers preserved with Eurocollins, with or without modification, than in the livers preserved with UW solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase

Liver cirrhosis in rats: regeneration and assessment of the role of phenobarbital.

A common model for producing experimental liver cirrhosis is the administration of CCl4 to phenobarbital (PhB)-stimulated rats. However, concern may arise due to the complex actions of PhB upon liver metabolism. This study examined the role of PhB in the production of CCl4-induced liver cirrhosis in the rat. In addition, regenerative capacity of the liver after partial hepatectomy (PH) or portal branch ligation (PBL) was studied in cirrhotic rats, rats treated with CCl4 alone, and in PhB-treated controls. In rats given PhB throughout the CCl4-induction period, ascitic form of micronodular cirrhosis was found in 93% with only 3% mortality. In contrast, rats pretreated with PhB for only 2 weeks followed by CCl4 alone for 18 weeks did not develop liver cirrhosis. In most of the cirrhotic rats, PH induced hepatic regeneration associated with improved liver histology. PBL was less effective. Treatment with PhB alone for 10 weeks resulted in liver atrophy and reduced hepatic regenerative capacity. Impaired regeneration response was also found in rats treated with CCl4 alone. In conclusion, treatment with PhB throughout the CCl4-induction period seems necessary for the production of liver cirrhosis in rats. However, prolonged treatment with PhB alone results in liver atrophy and an impaired regenerative response. Therefore, though necessary for the cirrhotic model, PhB by itself has negative hepatotrophic influences which questions the thoroughness of the PhB/CCl4 experimental model.

Animals

Phosphatidylcholine prevents postoperative peritoneal adhesions: an experimental study in the rat.

Phosphatidylcholine (PC) is the main constituent of the surface-active material coating peritoneal mesothelium. It may prevent postoperative adhesion formation through production of a lubricant film on mesothelial defects. We therefore examined the effect of its soluble form on surgically induced intraabdominal adhesions in rats. The adhesions were induced at laparotomy by any of four different operative models. PC was administered intraperitoneally (20 mg/rat) or intravenously (20 mg/rat or 50 mg/rat) at the end of the operation and on the second and third postoperative day. It was found that the degree of postoperative adhesion formation was significantly reduced by the intraperitoneal injection of PC in all 4 models. In contrast, no effect was achieved by the intravenous injection of PC, not even at a very high dose level. Our results suggest that soluble PC administered intraperitoneally might be a potent adjunct in postoperative adhesion prevention.

Abdomen

Intermittent hepatic arterial or portal occlusion reduces liver tumor growth.

The effect of repeated, intermittent hepatic vascular occlusion on liver tumor growth was studied in 32 rats. An adenocarcinoma was inoculated in the left liver lobe. After 8 days, the tumor size was measured and then, in three groups, the hepatic artery was occluded intermittently during 5 days for 15 min, 1 hr, or 2 hr daily, respectively. The tumor growth after 6 days in these groups was compared with that in a group where instead the portal vein was occluded intermittently during 5 days for 15 min, and with that in a group of sham-operated control rats. In the control rats, the tumor volume (mean +/- SEM) increased from 0.16 +/- 0.03 to 1.34 +/- 0.15 cm3 during the 6 days of experiment. It was found that repeated, intermittent occlusion of the hepatic artery or the portal vein, retarded the liver tumor growth to 30-60% of the growth rate in sham-operated controls (P less than or equal to 0.015). The 15-min daily hepatic artery or portal vein occlusion was found to reduce the tumor growth rate as much as daily hepatic artery occlusion for 2 hr. It is suggested that short, daily, intermittent hepatic vascular occlusions might be efficient in the palliative treatment of liver malignancy.

Adenocarcinoma

Metabolic responses to intermittent hepatic dearterialization in the rat.

Hepatic dearterialization is a palliative treatment for irresectable liver tumours. In the current study, the metabolic consequences of hepatic dearterialization were examined in the rat. Liver glycogen content was reduced to an average of 84% following 60 min dearterialization and was further reduced to an average of 16% following 60 min reperfusion. Plasma concentration of beta-hydroxybutyric acid was elevated by an average of 65% following 60 min hepatic dearterialization. In contrast, hepatic dearterialization did not alter cholesterol and triglyceride plasma levels. In addition, the hepatic activity of hepatic lipase was reduced by 29% after 60 min of hepatic dearterialization, a reduction which remained after 60 min of reperfusion. Clearance of intravenously administered antipyrine, which reflects the activity of liver microsomal enzymes, was reduced by 37% after 60 min of hepatic dearterialization. In conclusion hepatic dearterialization is accompanied by marked activity in the processes related to carbohydrate, lipid and xenobiotic metabolism. These effects should be taken into account when treating patients with hepatic dearterialization.

3-Hydroxybutyric Acid

Insulin secretion in streptozotocin-diabetic rats transplanted with immunoisolated islets.

Islet transplantation may be optimized by islet immunoisolation to prevent direct contact between the islet graft and the host tissue. In this study, we examined the glycemia and insulin secretion in streptozotocin-diabetic rats transplanted with islets subjected to immunoisolation with Algire diffusion chamber or with microencapsulation. Two days after diabetes induction by streptozotocin (70 mg/kg i.v.), rats were transplanted i.p. with either 1500 or 3000 islets encapsulated in Algire diffusion chambers, or with either 1500 or 3000 microencapsulated islets. Controls were diabetic rats transplanted i.p. with 1500 overnight-cultured islets not subjected to immunoisolation. In these controls, normoglycemia was evident for 3 weeks and a normal plasma insulin response to glucose infusion (10 mg/min) was seen at day 10 after transplantation. It was found that rats transplanted with 1500 microencapsulated islets similarly were normoglycemic for 3 weeks and that the plasma insulin response to glucose infusion at day 10 was normal. Furthermore, rats transplanted with 3000 microencapsulated islets remained normoglycemic for 6 months, and a glucose infusion performed at 6 months in these rats showed a normal acute plasma insulin response, whereas the second phase of insulin secretion was reduced. In contrast, rats transplanted with 1500 islets immunoisolated in Algire chamber remained hyperglycemic, and rats transplanted with 3000 islets within Algire chamber were normoglycemic for only 2 weeks. We conclude that microencapsulation is superior to the use of diffusion chamber as the immunoisolation technique for islets used for transplantation.

Alginates

The function of a colloid in liver cold-storage preservation.

The value of colloid in preservation of the liver by cold storage has not yet been fully clarified. Therefore, we studied the effects of colloid on cell swelling, liver weight, and bile production after cold storage in rat liver tissue slices and isolated rabbit liver. In rat liver tissue slices cold-stored for 24 hr in UW solution, total tissue water (TTW) was the same as in the control freshly unpreserved tissue and omitting the colloid (hydroxyethyl starch) from the UW solution did not affect the TTW. However, after cold storage for 24 hr in Perfadex, TTW was markedly increased (by 100%, P less than 0.001). Omitting the colloid in this solution, dextran, or replacing it with hydroxyethyl starch, did not affect this increase in TTW. Thus, the hypothermia-induced cell swelling evident after preservation in Perfadex was not prevented by colloid. Rabbit liver cold-stored in UW solution for 24 hr lost 15.4 +/- 4.7% of weight, but omitting the colloid from UW solution decreased this weight loss to 3.1 +/- 3% (P less than 0.01). In contrast, rabbit livers cold-preserved in colloid-free Perfadex gained 23.3 +/- 5.7% in weight. Adding colloid, either dextran or hydroxyethyl starch, decreased significantly this weight gain, to 9 +/- 3.7% and 10.4 +/- 1.8%, respectively (P less than 0.01), probably as a result of colloid osmotic pressure, preventing the interstitial edema. Rabbit livers preserved for 24 hr in UW solution, with or without colloid, produced the same amount of bile as control unpreserved livers. In contrast, livers preserved in colloid-free Perfadex for 24 hr had a markedly impaired bile production (3.9 +/- 0.9 ml/100 g) as compared with control livers (15.5 +/- 2.6 ml/100 g, P less than 0.01). Colloid partially restored this impaired bile production, to 8 +/- 1.4 mg/100 g by dextran and to 8.5 +/- 1.7 ml/100 g by hydroxyethyl starch, respectively (P less than 0.01). Thus, although colloids do not prevent the hypothermia-induced cell swelling, they prevent the development of interstitial edema, and, hence, improve the liver function.

Adenosine

Improvement of the effects of intrasplenic transplantation of hepatocytes after 90% hepatectomy in the rat by cotransplantation with pancreatic islets.

Acute liver failure is associated with high mortality. Whether support with transplanted hepatocytes improves the outcome is not established. We studied the potential beneficial effects of intrasplenic transplantation of hepatocytes in conjunction with islets of Langerhans on 90% hepatectomy-induced acute liver failure in rats. We found that all control rats died within 48 hr following 90% hepatectomy. In contrast, the mortality decreased significantly in rats transplanted with 10(7) hepatocytes into the spleen parenchyma at 1-3 days prior to 90% subtotal hepatectomy, whereas no significant reduction in mortality was seen in rats transplanted with hepatocytes immediately after the operation. However, cotransplantation of hepatocytes and 400 isolated pancreatic islets into the spleen reduced mortality when performed immediately after the 90% hepatectomy. Therefore, hepatocyte transplantation reduces mortality after 90% hepatectomy only if performed prior to the hepatectomy. However, transplantation of hepatocytes in conjunction with pancreatic islets reduces mortality when performed at the same time as 90% hepatectomy. Hence, the combined transplantation of hepatocytes and islets might offer support after liver failure.

Alkaline Phosphatase

Islet allotransplantation to streptozotocin-diabetic rats. Effects of multistrain donation and ultraviolet light irradiation.

It has previously been suggested that rejection after islet transplantation in mice is prevented by using a small amount of islet tissue from several donor animals of different strains. Furthermore, it has been suggested that ultraviolet light (UV) irradiation of islet grafts prevents rejection. We therefore studied whether islet allotransplantation in the rat could be improved by using islets from donor rats of several different strains or by using UV-irradiated islets. We found that Sprague-Dawley rats transplanted with 1,000 Wistar rat islets 2 days after streptozotocin (70 mg/kg, i.v.) remained normoglycemic for only 8 +/- 1 days. The same poor result was obtained when the diabetic rats were transplanted with islets collected from donor rats of four different strains, also when only 100 islets from each donor rat were used in combination with short-term insulin treatment. In contrast, streptozotocin-diabetic Sprague-Dawley rats isotransplanted with either 1,000 islets or with 400 islets combined with a short-term insulin treatment remained normoglycemic for more than 3 months. Furthermore, rats allotransplanted with 400 UV-irradiated islets and also treated with ciclosporin remained normoglycemic for 30 +/- 3 days, whereas those transplanted either with 400 UV-irradiated islets without ciclosporin treatment or with 400 nonirradiated islets with ciclosporin treatment did not reach normoglycemia. We conclude that, in rats, multistrain islet donation is not efficient and that UV irradiation of islets does not result in long-term benefits.

Animals

Improved liver preservation for transplantation due to calcium channel blockade.

Intracellular calcium is an important determinant for cell death in organ hypothermic preservation for transplantation. In this study, we show that prevention of calcium entry improves the result of liver cold storage in UW solution. The isolated perfused rabbit liver was used. After 48 hr of cold storage in UW solution, bile production was reduced by 70% (P less than 0.005). However, by adding the calcium channel blockers verapamil or nifedipine (40 microM) to the UW solution, this reduction was abolished, and the livers produced the same amount of bile as unpreserved livers. Furthermore, addition of the calcium channel activator, BAY K8644 (40 microM), to the UW solution, reduced bile production by 50% (P less than 0.01) already after preservation for 24 hr. We conclude that calcium entry is of importance for liver function after preservation and cold storage, and that including a calcium channel blocker to the preservation solution makes long-term liver preservation safer.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Repeated dearterialization of hepatic tumors with an implantable occluder.

A new implantable device for repeated hepatic dearterialization was evaluated in 13 patients with tumors of the liver. Eleven patients had colorectal secondaries and also received cyclic intraperitoneal infusion of 5-fluorouracil. Two patients had primary hepatocellular cancer (HCC). Four patients had a variant arterial supply. The hepatic artery was occluded repeatedly for 1 hour twice daily for 1 to 17 months (mean, 8.5 months). A complete transient occlusion was obtained in all but three patients, in whom minor collaterals were missed at the initial operation. Collaterals developed in two patients during therapy. Leakage from the balloon occurred in two patients after 5 and 12 months. Two patients developed thrombosis of the hepatic artery during therapy due to the cuff being placed too tightly around the vessel. A complete remission was demonstrated in one patient with HCC, a partial response in three patients (one HCC and two metastatic), stable disease in two patients, and progression in five patients. Median survival for colorectal lesions was 15 months (range, 2 to 23 months) from start of the occlusions. Four of nine patients developed calcifications of their lesions during therapy. One patient with HCC was alive and free of disease 18 months after the start of the occlusions. Both patients with HCC had an obstructed portal vein which may have contributed to the favorable outcome. The occluder was uniformly accepted by the patients who were able to do their occlusions at home.

Adult

Roles of bile and bacteria in biliary peritonitis.

Bile is known to have an adverse effect in peritonitis but the mechanism(s) and site of action of bile are unknown, as are the relative roles of bile and bacteria. The present study was designed to answer some of these questions. Experiments in which rats were injected intraperitoneally and intravenously with bile, Escherichia coli or saline showed that bile had no systemic toxicity and that it increased the mortality rate only when introduced into the peritoneal cavity together with bacteria. Measurements of peritoneal fluid volumes and blood pressure did not confirm the theory that the increased mortality rate was a consequence of loss of plasma volume into the peritoneal cavity. The number of intraperitoneal bacteria decreased continuously in animals receiving intraperitoneal E. coli alone. When bile was added by intraperitoneal injection, the number of intraperitoneal bacteria started to rise at 2 h and then increased steadily with a consequent bacteraemia at 10 h. The number of bacteria per peritoneal phagocyte was significantly lower after intraperitoneal injection of E. coli and bile, when compared with injection of E. coli alone. It is concluded that bile exerts its detrimental effect within the peritoneal cavity in the presence of bacteria. Bile impairs local host defence in a way that remains unknown and may be related to the detergent-lytic effects of bile salts.

Animals

Intermittent hepatic dearterialization induces glucose intolerance: an experimental study in the rat.

Intermittent hepatic dearterialization is used in the palliative treatment of liver malignancy. However, its metabolic consequences are not established. Therefore the influences of the procedure on the plasma insulin, glucagon and glucose responses were studied in healthy rats and in rats with a tumour inoculated subcapsularly into the liver. To study the influence on stimulated islet hormone secretion we infused arginine intravenously (7 mg/min) for 30 min, because arginine is known to stimulate the secretion of both insulin and glucagon. During hepatic dearterialization, hyperglycaemia developed; mean(s.e.m.) blood glucose levels after 60 min of dearterialization were 20.2(1.3) mM versus 14.7(1.5)mM in controls (P less than 0.001). Concomitantly, compensatory hyperinsulinaemia and hypoglucagonaemia occurred. Furthermore, during both dearterialization and in the immediate reperfusion phase, the arginine-induced increase in plasma insulin levels was impaired (P less than 0.001), whereas the arginine-induced increase in plasma glucagon levels was not significantly affected. These changes were qualitatively the same in tumour-free and tumour-bearing rats. We conclude that glucose intolerance develops during selective hepatic dearterialization, which is evident both from basal hyperglycaemia and impaired insulin secretion.

Adenocarcinoma

A technique for isolated liver perfusion in the rat with survival and results of cytotoxic drug perfusion on liver tumor growth.

The toxic side effects of many chemotherapeutic agents prevent their use in high concentrations. Isolated perfusion techniques have been used most commonly for malignancies involving the extremities, but recently also for irresectable liver tumors. This paper describes a technique for in vivo isolated liver perfusion for 30 min with oxygenated blood through the portal vein and hepatic artery simultaneously. There was a 14% mortality rate. There was some initial hepatocellular death, which resolved quickly and did not seriously affect liver function. There was only a small leak from the perfusion system to the systemic circulation. We tested the system on an experimental liver tumor from a colonic adenocarcinoma. Perfusion with added 5-FU in a toxic dose of 70 mg/kg to the medium significantly retarded tumor growth evaluated 10 days after perfusion compared to rats perfused without 5-FU. This model closely resembles the technique applied clinically and will enable further work on effects of perfusion in an experimental rat liver tumor model.

Animals

Bile peritonitis in acute cholecystitis.

A review of all patients treated for acute cholecystitis (n = 5848) during an 18-year period (1969-1986) at two hospitals (one practising early surgery in patients with acute cholecystitis and the other not) disclosed that 104 (1.8%) had bile within the abdominal cavity at surgery; 71 with a visible perforation of the gallbladder and 33 without. The bile was infected in 82% of performed cultures (most commonly with Escherichia coli). Mortality was 7.7% (8/104 patients), being 20% (4/20) in the hospital practising delayed surgery and 5% (4/84) in the hospital practising early surgery (p less than 0.10). Infectious complications were responsible for the deaths by leading to multiple organ failure with pulmonary or renal insufficiency or gastro-intestinal bleeding. The timing of surgery was the only factor that had prognostic significance, i.e. the longer the hospital delay before surgery the higher the mortality, although elderly patients or patients with perforation tended to have a worse prognosis. In conclusion, the results of this study indicated that early surgery is important in patients with acute cholecystitis as a means of lowering mortality in bile peritonitis in this condition.

Acute Disease

Percutaneous management of pyogenic hepatic abscesses.

Twelve patients (9 men, 3 women) with a mean age of 65 (54-78) years, with pyogenic hepatic abscesses were managed by percutaneous drainage between 1979 and 1987. Biliary origin was most common (4 patients), followed by hepatic abscesses as a late postoperative complication (seen in 3 patients) and hepatic abscesses occurring in association with acute appendicitis (2 patients). The origin was unknown in 3 patients. Diagnosis was reached by computed tomography or ultrasonography with a diagnostic delay of in mean 11 days. Seventeen abscesses were found among the 12 patients. The median abscess size (maximal diameter) was 7 (1-12) cm. Nine patients were treated with percutaneous drainage with an indwelling catheter within the abscess cavity for up to 3 weeks, while 3 patients were managed with percutaneous puncture and aspiration alone. The most commonly isolated organism from the drained hepatic abscess was E. coli. The course following percutaneous treatment was uneventful, without mortality and recurrence of the hepatic abscess during follow-up. One patient required surgical drainage of an additional hepatic abscess. Percutaneous drainage of hepatic abscesses, independent of origin, thus seems as a safe and reliable method, which should be considered as the treatment of choice if facilities and knowledge of percutaneous management are provided.

Aged