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Biomedical subjects

E Klar

Publications and source records attributed to E Klar.

At least 145 records · Page 8Linked to original sources
PubMed1995

Improved survival in acute necrotizing pancreatitis despite limiting the indications for surgical debridement.

OBJECTIVE: To reassess our criteria for the stratification of attacks of acute pancreatitis, and indications for operation in patients with necrotising pancreatitis. DESIGN: Retrospective analysis of casenotes. SETTING: University Hospital, Germany. SUBJECT: 341 Consecutive patients who presented with a first attack of acute pancreatitis between December 1979 and January 1991. MAIN OUTCOME CRITERIA: Morbidity and mortality in relation to clinical (Ranson, Kümmerle, Goris) and radiological (Balthazar) criteria. RESULTS: 78 Patients developed necrotising pancreatitis judged radiologically. Mortality was 15/38 (39%) in the period 1980-85 and 6/40 (15%) in the period 1986-1990. During the first period patients were operated on if their unfavourable clinical signs did not start to resolve within 72 hours, whereas in the second period operation was restricted to those patients who developed signs of multiple organ failure. This policy resulted in the number of operations being reduced from 26/38 (68%) to 17/40 (42%), respectively (p = 0.03). CONCLUSION: Our data support the policy of restricting surgical debridement in necrotising pancreatitis to those patients who develop signs of multiple organ failure.

Acute Disease↗
PubMed1995

[Induction of impaired hepatic microcirculation by in situ hilus preparation in liver explantation].

AIM: Usually, in-situ preparation of the hepatic hilar structures is performed prior to the perfusion with preservation solution. Aim of this study was to investigate mechanical effects of liver preparation on the hepatic microcirculation. METHODS: 16 pigs (German landrace) were randomized in two groups. In both groups, laparotomy was performed after intratracheal intubation. Subsequently, a thermal diffusion probe was implanted into the medial left liver lobe for quantification of microperfusion. In group A (n = 8), bile duct, hepatic artery, and portal vein were exposed and the lesser omentum transsected thereafter. Ultrasound-volume-probes were placed around the hepatic artery and portal vein. Simultaneous measurement of hepatic microperfusion and total liver blood flow was performed five minutes after the end of liver preparation. In group B (n = 8) hepatic microperfusion was quantified 45 minutes after laparotomy without further manipulations. RESULTS: By the preparation, liver perfusion was significantly reduced in group A from 78 +/- 13 ml/100g/min to 61 +/- 16 ml/100g/min. After preparation a total liver blood flow of 137 +/- 46 ml/100g/min was recorded indicating a shunt fraction of 51 +/- 21%. In contrast, hepatic microperfusion in group B remained at baseline during the whole observation period (79 +/- 3 ml/100g/min vs. 78 +/- 5 ml/100g/min). CONCLUSION: In-situ liver preparation induces a relevant disturbance of hepatic microcirculation. Preservation perfusion shortly after surgical manipulation could become ineffective because of an increase in shunt flow. If the regeneration period is too short, e.g. lack of heart explantation, the quality of the liver graft could be limited.

Animals↗
PubMed1995

The role of bile acid secretion in the hepatic response to operation and infection.

Hepatic function is altered in many surgery-related diseases. Bile acid secretion is the major determinant of bile formation and an important indicator of overall hepatic function. To investigate the cause of intrahepatic cholestasis, which is frequently associated with sepsis, we studied the effects of cecal ligation and puncture (CLP) and surgical stress on bile acid secretion and composition. CLP or a sham operation was performed on 20 male Sprague-Dawley rats. Bile was collected from each rat by cannulation of the common bile duct for 10-minute intervals, at 5 and 20 hours after the initial procedure. Bile acid analysis was then performed by high performance liquid chromatography (HPLC). In CLP rats, there was a significant (P < 0.05) cholestatic effect. Bile flow was reduced to 70 +/- 13 per cent at 5 hours, and to 55 +/- 16 per cent at 20 hours (per cent of the sham mean value). In the sham-operated rats, there was a significant choleresis at 20 hours. Bile flow was increased to 146 +/- 13 per cent; bile acid secretion to 245 +/- 24 per cent; and total bile acid concentration to 175 +/- 19 per cent of the sham 5-hour value (P < 0.05). This increased secretion was significantly greater in the metabolites of chenodeoxycholate. However, these surgical stress-associated changes in bile acid secretion and composition did not occur in CLP rats. These findings are consistent with surgical stress-induced induction of 7 alpha-hydroxylase, which was not found in the septic animals. These observations may provide useful insights into the early stages of the pathogenesis of sepsis-related hepatic dysfunction and failure.

Animals↗
PubMed1994

Exocrine hyperstimulation but not pancreatic duct obstruction increases the susceptibility to alcohol-related pancreatic injury.

OBJECTIVE: To evaluate the factors thought to be involved in the pathogenesis of acute pancreatitis associated with alcohol. BACKGROUND: The mechanism of alcohol-induced pancreatitis is believed to involve synergistic effects of various pathogenetic factors. The present study was designed to evaluate the possible contribution of pancreatic duct obstruction, physiologic exocrine stimulation, or secretory hyperstimulation to alcohol-induced pancreatic injury. METHODS: Wistar rats were allocated randomly to a control group (group 1), or to a group with pancreatic duct obstruction (group 2), physiologic exocrine stimulation (group 3), ductal obstruction and exocrine stimulation (group 4), or exocrine hyperstimulation with the cholecystokinin analogue cerulein (group 5). Three hours after this pretreatment, animals in each experimental group were randomly divided into two subgroups for intragastric administration of either water (groups 1A through 5A) or beer (groups 1B through 5B). Test solutions were instilled over 9 hours (total amount of alcohol administered, 4.8 g/kg). Twenty-four hours after beginning the test infusion, animals were killed for histologic evaluation of pancreatic edema and determination of an acinar cell necrosis score. Serum amylase levels were determined at 3, 9, and 24 hours. RESULTS: No increase in amylase levels or significant morphologic changes were found in control animals (group 1A) or in animals subjected to physiologic exocrine stimulation (group 2A). Pancreatic duct obstruction, with or without physiologic exocrine hyperstimulation (groups 3A and 4A), and exocrine hyperstimulation (group 5A) induced pancreatitis of similar severity with minor acinar cell damage. Alcohol superimposed on exocrine hyperstimulation (group 5B) increased acinar cell injury (group 5A, 0.4 +/- 0.1 points vs 5B, 1.0 +/- 0.2 points; P < .05) and serum amylase levels at 24 hours (group 5a, 41 +/- 6 U/L vs group 5B, 72 +/- 11 U/L; P < .05), whereas no differences between subgroups A and B (water vs beer) were found in groups 1 through 4. CONCLUSION: Our findings suggest that the pathogenesis of acute alcoholic pancreatitis may require a state of exocrine hyperstimulation, perhaps via cholecystokinin, but do not support a role for constriction or obstruction of Oddi's sphincter.

Acute Disease↗
PubMed1994

Impact of microcirculatory flow pattern changes on the development of acute edematous and necrotizing pancreatitis in rabbit pancreas.

Impairment of pancreatic microcirculation has often been advocated as one pathogenic mechanism in necrotizing pancreatitis. In contrast, data on pancreatic capillary perfusion in edematous pancreatitis are scarce. It was the aim of this experimental study to compare changes in pancreatic microcirculation in edematous and necrotizing pancreatitis. Twelve rabbits were allocated to two groups. Two different models of acute pancreatitis were used. Edematous pancreatitis was elicited by intravenous administration of cerulein (25 micrograms/kg/hr) (N = 6). Necrotizing pancreatitis of the biliary type was induced by pressure-controlled intraductal infusion of a mixture of taurocholate, trypsin, and blood (N = 6). Pancreatic microcirculation was quantified by means of intravital microscopy assessing functional capillary density, blood cell velocity, and distribution of the plasma marker FITC-dextran 70. Systemic hemodynamics were maintained at baseline values by fluid administration. Regardless of edema or necrosis, pronounced extravasation of FITC-dextran was recorded in the early stage of pancreatitis. In cerulein-induced pancreatitis, hyperemia developed as indicated by an increase in blood cell velocity in the presence of homogeneous capillary perfusion. In contrast, a progressive reduction of the number of perfused capillaries was detected in necrotizing pancreatitis. In conclusion, pancreatic microvascular perfusion may be regarded as an important pathogenetic factor for the determination of acute pancreatitis.

Acute Disease↗
PubMed1994

Intraoperative evaluation of big-endothelin plasma levels during liver transplantation in different vascular compartments.

Endothelin-1 (ET) is derived from its precursor big-ET, secreted by endothelial cells of multiple origin. The role of ET peptides in the physiological responses after orthotopic liver transplantation (OLT) was investigated. Venous big-ET plasma levels were analysed by RIA in 28 patients before and after OLT. Samples for analysis were taken intraoperatively from 12 patients from the caval, portal and hepatic veins and the radial artery at multiple time points. Highest caval levels were found during the anhepatic period and 60 min after reperfusion, followed by a drop and subsequent increase postoperatively. Highest levels in the hepatic and portal veins were detected during explanation and reperfusion. A different pattern was found in the radial artery. Values during rejection and infection were elevated compared with preoperative and postoperative levels. The heterogeneity of the kinetics points to different sites of ET generation, including liver and splanchnic circulation. It suggests a predominant paracrine secretion mode of ET peptides with various stimuli involved. Big-ET levels could reflect endothelial cell damage, as big-ET is generated intracellularly and biological activity is rather weak.

Adult↗
PubMed1993

Isovolemic hemodilution with dextran 60 as treatment of pancreatic ischemia in acute pancreatitis. Clinical practicability of an experimental concept.

OBJECTIVE: This phase-I study transferred the concept of isovolemic hemodilution, which has been proven beneficial in the treatment of experimental acute pancreatitis to the patient. SUMMARY BACKGROUND DATA: Pancreatic ischemia represents one main mechanism in the pathogenesis of necrotizing pancreatitis. Isovolemic hemodilution with dextran 60 has been shown experimentally to limit the progression of pancreatic necrosis by improving pancreatic microcirculation. METHODS: Thirteen patients with clinically severe nonbiliary pancreatitis and CT-classification E according to Balthazar were enrolled. Exclusion criteria were anemia, coronary heart disease, chronic obstructive pulmonary disease, coagulopathies, and secondary referral. The volume of blood to be exchanged for dextran 60 was calculated from a nomogram based on body surface. Isovolemic hemodilution aimed at a hematocrit of 30%. Independent from the exchange procedure conventional fluid resuscitation was performed to adjust the central venous pressure at 6 +/- 2 mm Hg. RESULTS: Whole blood (750-1,700 mL) was exchanged for dextran 60 during 45 to 70 minutes. No adverse effect was encountered; central hemodynamics were not affected. Considering a mean Ranson score of 5, mortality was low (7.7%). Progression of pancreatic necrosis was registered in only two patients subsequently undergoing surgical treatment (15%). CONCLUSIONS: Isovolemic hemodilution is practicable in patients. A randomized trial has to prove whether isovolemic hemodilution can substantially alter the course of acute pancreatitis as anticipated from animal studies.

Acute Disease↗
PubMed1993

Improvement of impaired pancreatic microcirculation by isovolemic hemodilution protects pancreatic morphology in acute biliary pancreatitis.

Impairment of the pancreatic microcirculation is a characteristic finding in experimental biliary pancreatitis. Isovolemic hemodilution with dextran 60 has been proven to maintain pancreatic capillary perfusion. To evaluate the significance of this therapeutic approach with respect to histologic changes, intravital microscopic assessment of the microcirculation was combined with a morphometric analysis of the pancreas by means of light microscopy in rabbits (n = 18). Pancreatic capillary perfusion was maintained in the rabbits subjected to hemodilution 30 minutes after the induction of pancreatitis with 54 percent of the capillaries still being perfused at 12 hours, compared with only 16 percent in the control group. The improved capillary perfusion resulted in a significant reduction of those changes considered potentially reversible (cell vacuolization and interstitial edema) that surround zones of necrosis. However, because of the early establishment of necrosis in this model, hemodilution was unsuccessful in preventing all cell death. Hemodilution can limit the progressive extension of pancreatic injury in this model of biliary pancreatitis.

Acute Disease↗
PubMed1992

[Etiology and pathogenesis of acute pancreatitis].

The pathogenesis of acute pancreatitis is based on the following principles: 1. Biliary. In biliary pancreatitis there is a causal relationship between the induction of acute pancreatitis and the migration of gallstones. The basic pathomechanism seems to be a combination of an increase in permeability and pressure in the ductal system. 2. Intraacinar. Caerulein-pancreatitis is a well established experimental model which reflects the intracellular/interstitial type of activation. Basolateral secretion of pancreatic enzymes into the interstitial space represents the initial event. Intracellular activation of trypsin by the fusion of zymogen-granules and lysosomes has been advocated as an alternative mechanism. 3. Alcohol. The acute alcohol pancreatitis comprises a combined pathogenesis. Obstruction and reflux as well as the cytotoxic effect of alcohol seem to be the main principles. 4. Disturbance of pancreatic microcirculation. Ischemia of the pancreas seems to play a key role in the transition from pancreatic edema to necrosis. Improvement of capillary perfusion by isovolemic hemodilution with dextran 60 has been shown to be an efficient therapeutic tool.

Acute Disease↗
PubMed1991

Adverse effect of therapeutic vasoconstrictors in experimental acute pancreatitis.

Alpha-adrenergic drugs commonly are used to treat hypotension resulting from severe acute pancreatitis. It was shown previously that although systemic arterial pressure is increased by phenylephrine, pancreatic microcirculatory perfusion is decreased. Because inadequate tissue perfusion may be critical in the progression of edematous pancreatitis to parenchymal necrosis, it was hypothesized that vasoconstrictors might be harmful in pancreatitis. Therefore the effect of phenylephrine on cerulein-induced mild pancreatitis were studied. Sprague-Dawley rats (n = 54) were randomly allocated to 6 experimental groups and subjected to the following infusion regimens: (1) cerulein (cae) + phenylephrine (phe), (2) cae + saline (NS), (3) NS + phe, (4) cae + phenoxybenzamine (pbz) + phe, (5) NS + pbz + phe, and (6) NS. Initial and terminal hematocrit, serum amylase activity, and blood ionized calcium concentration were determined. The animals were killed 9 hours after starting the infusion. Macroscopic and histologic changes were scored by a 'blinded' pathologist. Phenylephrine increased the severity of cerulein-induced pancreatitis as manifested by statistically significant adverse changes in serum amylase, hematocrit, ionized calcium, peripancreatitic soap formation, and acinar cell vacuolization. These changes were antagonized by alpha-adrenergic receptor blockade with phenoxybenzamine. It is concluded that phenylephrine is deleterious in acute experimental pancreatitis, the first demonstration of such an effect by a pharmacologic vasoconstrictor, and suggested that microcirculatory changes may be important in the transition of mild to severe pancreatitis. Caution in the use of vasoconstrictor drugs in patients with acute pancreatitis is recommended.

Acute Disease↗
PubMed1991

[The value of classification for therapy and prognosis of acute pancreatitis. Analysis of a patient sample of the Heidelberg Surgical University Clinic 1986-1989].

116 patients admitted for acute pancreatitis were analysed. In 80% of patients presenting biliary pancreatitis cholecystectomy and bile duct exploration was the prevalent treatment, in 7.8% pancreatic necrosis was removed. Indications to operate on patients with non-biliary pancreatitis included enhancement of pancreatic inflammation revealed by computed tomography and multi-organ-failure or sepsis complicating the course of the disease (incidence of laparotomy 20.3%, incidence of necrosectomy 12.3%). According to this concept 2 out of 3 patients presenting partial pancreatic necrosis recovered without operation. Lethality of patients with acute necrotizing pancreatitis (6.9%) was accounted 25%, over-all mortality 6%. Methods used for classification of severity of acute pancreatitis (Mainz classification, Ranson criteria) turned out to be not reliable. Clinical staging of pancreatitis was not in accordance with intraoperative findings in 51.9% of cases. As a prerequisite for stage-dependent therapy new objective data to access severity and clinical course of acute pancreatitis have to be worked out.

Acute Disease↗