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E Klar

Publications and source records attributed to E Klar.

At least 127 records · Page 7Linked to original sources
PubMed1996

Benefits of various dextrans after delayed therapy in necrotizing pancreatitis of the rat.

OBJECTIVE: Ultrahigh-molecular dextran (500,000 Da) has been shown to prevent pancreatic necrosis when given 30 min after induction of pancreatitis. This study should clarify the following: (a) are dextrans still effective after prolongation of the therapy-free interval? (b) what is the impact of the molecular weight of the dextrans? and (c) is their effect influenced by the dextran concentration or by the addition of hypertonic saline? ANIMALS AND INTERVENTIONS: Acute pancreatitis was induced in 70 male dextran-tolerant Wistar rats using intraductal bile-salt infusion and intravenous hyperstimulation. After 3 h, animals were assigned to one of seven groups (n = 10 per group) receiving either Ringer solution or different dextrans (10%) including 70,000 Da (DEX-70), 160,000 Da (DEX-160), 300,000 Da (DEX-300) or 500,000 Da (DEX-500). Additional groups included DEX-70 (6%) and DEX-70 (10%) in combination with hypertonic NaCl (7.5%) (HHS-70). Ringer solution was given at 24 ml/kg and all dextrans at 8 ml/kg. MEASUREMENTS AND RESULTS: Trypsinogen activation peptides (TAP) were quantified in ascites and acinar necrosis after death or sacrifice at 9 h. As an index of less pathological trypsinogen activation, the mean TAP levels in ascites were significantly lower in DEX-70 and DEX-160 compared to Ringer controls (p < 0.05, t-test). Furthermore, the amount of acinar necrosis was significantly lower in all dextran groups except the HHS-70 in comparison with Ringer controls (p < 0.01, t-test). Finally, mortality was significantly reduced from 60% in Ringer controls to 10 and 0%, respectively, in the groups treated with DEX-70 and DEX-160 (p < 0.03, Fisher's Exact test). There was a similar trend in all other groups except the HHS-70. CONCLUSIONS: Despite a therapy-free interval of 3 h, dextrans reduce trypsinogen activation, prevent acinar necrosis, and improve survival in necrotizing rodent pancreatitis. The molecular weight and concentration of dextran are of secondary importance for these beneficial effects.

Animals↗
PubMed1996

Improvement of pancreatic capillary blood flow does not augment the pancreatic tissue concentration of imipenem in acute experimental pancreatitis.

BACKGROUND: Acute necrotizing pancreatitis (ANP) is characterized by decreased capillary pancreatic blood flow. Thus, antibiotics may not reach pancreatic necrosis in therapeutic concentrations and consequently fail to prevent bacterial infection of the pancreas which today is the major cause of morbidity and mortality in ANP. OBJECTIVE: To evaluate whether improvement of impaired pancreatic microcirculation by isovolemic hemodilution with dextran leads to an increase in the pancreatic tissue concentration of imipenem (IMI), an antibiotic widely used in clinical ANP. METHOD: After induction of ANP rats were randomized for either standard fluid therapy with Ringer's lactate (RL) or isovolemic hemodilution with dextran 70,000 (IHD/DEX). Thereafter the animals received an intravenous injection of IMI, and 15 min later they were sacrificed for determination of IMI in serum and tissue. Capillary pancreatic blood flow (CPBF) at the time of antibiotic therapy was assessed by intravital microscopy in an additional set of animals. RESULTS: There was no significant difference in the pancreatic tissue concentration of IMI in animals pretreated with either RL (11.7 +/- 0.6 micrograms/g) or IHD/DEX (11.4 +/- 1.4 micrograms/g), although CPBF was significantly increased in the latter group (1.3 +/- 0.05 vs. 0.8 +/- 0.04 nl/min/capillary). CONCLUSION: (1) IMI is concentrated by the pancreas in experimental ANP despite impaired CPBF. (2) Enhancement of pancreatic capillary blood flow by IHD/DEX does not increase the pancreatic tissue concentration of IMI. This suggests that CPBF is not a decisive factor influencing the accumulation of this antibiotic in the pancreas, which may be one reason for the high efficacy of IMI in clinical ANP.

Acute Disease↗
PubMed1996

[Etiology and pathophysiology of acute pancreatitis].

The pathophysiology of acute pancreatitis can be divided into four different pathogenetic principles. 1. Ductular: The ductular pathogenesis is characterized by the frequent association between migrating gallstones and acute pancreatitis. The causative mechanism consists of an intraductal pressure and permeability increase with consecutive premature enzyme activation. 2. Acinar: The acinar pathogenesis is based on autoactivation of pancreatic enzymes after misdirected basolateral secretion into the interstitium of the pancreas and/or by colocalization of lysosomes and proenzyme-rich zymogen granules inside the acinar cell. 3. Mixed ductular-acinar: The main entity of this pathophysiological concept is the acute alcohol pancreatitis. An increase of intraductal pressure, of duct permeability and a possible direct toxic effect seem to be responsible. 4. Microcirculation disturbance: An impairment of pancreatic microcirculation appears to play a key role in the progression of edematous to necrotizing pancreatitis and was demonstrated in all models of necrotizing pancreatitis examined so far. Causative factors are poor blood fluidity by hemoconcentration, intravascular hypercoagulability, an impairment of arteriolar inflow by vasospasms, of capillary flow by direct endothelial injury and edema, of venous outflow by thrombosis, leukocyteendothelium interaction and direct toxic injury by activated enzymes, kinins and other mediators. A specific and therapeutically successful approach represents the administration of dextran which antagonizes both systemic and local causes of microcirculatory impairment.

Acute Disease↗
PubMed1996

[pHi value as a prognostic parameter in septic and polytrauma patients].

In 17 patients in septic shock and in 12 trauma patients (ISS > or = 20) the gastric pHi and systemic oxygen delivery and consumption were measured every 6 h to evaluate the prognostic significance of the pHi and to determine the relationship between the gastric mucosal oxygenation and the systemic oxygen transport parameters. In the trauma patient the initial pHi has a high prognostic significance (mean survivors = 7.38; non-survivors = 7.15; p < 0.05), while in the septic group no patient with a pathologic pHi (< 7, 35) > or = 12 h survived. Since we found no correlation between pHi and systemic oxygen transport parameters, other factors have to be of greater importance for gut mucosal oxygenation.

Critical Care↗
PubMed1995

Soluble thrombomodulin--a marker of reperfusion injury after orthotopic liver transplantation.

Thrombomodulin is an endothelial cell membrane protein that is released into the blood in soluble forms (soluble thrombomodulin [sTM]) in response to endothelial cell damage. We evaluated intraoperative sTM as a marker of reperfusion injury in 29 liver transplant recipients using an ELISA. Preoperative sTM levels were significantly elevated, as compared with healthy control subjects (75 +/- 61 ng/ml vs. 17 +/- 10 ng/ml; P < 0.001) and remain unchanged at the end of the anhepatic phase (58 +/- 40 ng/ml). There is an increase to 194 +/- 182 ng/ml 3 min after reperfusion (P < 0.001). Post-reperfusion sTM levels correlate significantly with the early liver enzyme release (aspartate transaminase) (P < 0.001). Patients with pronounced reperfusion injury (postreperfusion arterial sTM > 138 ng/ml, n = 16) present significantly higher maximum aspartate transaminase levels within the first 24 postoperative hr, as compared with patients with less reperfusion injury (arterial sTM < 138 ng/ml, n = 12) (P = 0.001). Released sTM is derived from the graft, since patients with pronounced reperfusion injury present significantly higher sTM levels in the hepatic vein 3 min after reperfusion compared with the portal vein (P < 0.001) and artery (P = 0.025), respectively. In patients with higher reperfusion injury, we found significantly more adherent intrasinusoidal granulocytes in the liver biopsy taken 1 hr after reperfusion (P = 0.006), indicating an interrelation of endothelial damage and the important phenomenon of "leukocyte sticking" in reperfusion injury. Thus the postreperfusion increase of sTM as a marker of reperfusion injury correlates with the early liver enzyme release and the accumulation of intrasinusoidal granulocytes.

Adolescent↗
PubMed1995

Determination of plasma activities of purine nucleoside phosphorylase by high-performance liquid chromatography: estimates of nonparenchymal cell injury after porcine liver transplantation.

An assay is described for measurement of purine nucleoside phosphorylase (PNP) in plasma by high-performance liquid chromatography (HPLC). A plasma sample was incubated with hypoxanthine and ribose-1-phosphate in phosphate-free medium at pH 7.4 to catalyse the production of inosine by plasmatic PNP. The reaction was stopped by addition of perchloric acid to inactivate the enzyme and to precipitate plasma proteins. After centrifugation and neutralization of the supernatant with NaOH the increase in the substrate inosine was determined by HPLC. Plasma activities of PNP averaged 5.0 mU/ml before and 12.3 mU/ml (p < 0.001), 5 min after porcine liver transplantation. At the same time points, the plasma activities of the frequently used liver enzymes lactate dehydrogenase or alanine aminotransferase remained virtually unchanged. Thus, plasmatic activities of PNP may be a suitable and early indicator of ischemic alterations to the graft in vivo.

Alanine Transaminase↗
PubMed1995

Alcohol selectively impairs oxygenation of the pancreas.

BACKGROUND: Alcohol predisposes to acute pancreatitis by an unknown mechanism and is known to reduce regional pancreatic blood flow. OBJECTIVE: To investigate whether increased blood alcohol causes functional impairment of pancreatic microperfusion as indicated by reduced tissue oxygenation. DESIGN: Prospective, randomized, controlled study. SETTING: University hospital laboratory. SUBJECTS: Forty adult female Wistar rats. INTERVENTIONS: Intravenous infusion of ethanol (2 g/kg) or saline over 60 minutes. Tissue hemoglobin oxygenation saturation and hemoglobin content were measured using reflectance spectroscopy in the pancreas, stomach, and kidney at baseline and at 10-minute intervals for 1 hour. RESULTS: Blood ethanol levels (mean +/- SEM) peaked at 1810 +/- 94 mg/L. Compared with saline controls, pancreatic hemoglobin oxygen saturation in ethanol-treated rats had significantly decreased by 40 minutes and remained depressed, while pancreatic hemoglobin content was unchanged. The magnitude of the depression was at least as great as that previously observed in acute experimental pancreatitis of moderate severity. Neither hemoglobin oxygen saturation nor hemoglobin content was affected in the stomach or kidney by ethanol. CONCLUSION: A raised blood ethanol level was associated with acutely decreased hemoglobin oxygen saturation in the pancreas but not in the stomach or kidney. This observation of provoked hypoxia provides a possible mechanism by which alcohol contributes to pancreatic injury.

Animals↗
PubMed1995

Summary of the 112th Annual Meeting of the German Society of Surgery. Berlin, April 18-22, 1995.

The Annual Meeting of the German Society of Surgery is the main clinical and research forum for the German surgical community. The venue, which was Munich for the past few decades, was changed to Berlin this year in commemoration of the foundation of the society in 1872 in the former and new German capital. Over 3000 surgeons, internists, and basic scientists took part in this year's meeting, which consisted of 1035 presentations. Only single aspects of the meeting can be described: those that are thought either to represent the mainstream of surgical progress in Germany or to depict socioeconomic problems of general interest.

Ambulatory Surgical Procedures↗
PubMed1995

Measurement of blood flow in pancreatic exchange capillaries with FITC-labeled erythrocytes.

Characterization of pancreatic capillary blood flow by in vivo microscopy has been limited by technical shortcomings associated with the use of plasma tracers and the lack of quantitative data. Therefore, fluorescent-labeled erythrocytes were evaluated for quantitation of pancreatic capillary blood flow in rats in physiological state and under defined conditions of increased and impaired pancreatic blood flow. Physiological blood flow was 1.21 +/- 0.06 nl/min per capillary with stable capillary perfusion pattern. Reduction of pancreatic blood flow by decreasing systemic arterial pressure to 60 mmHg through controlled hemorrhage produced a profound decrease of volumetric flow to 0.21 +/- 0.05 nl/min (P < 0.05). The number of perfused capillaries was reduced to 52 +/- 8% of baseline (P < 0.001) and the intermittent perfusion pattern was altered in 26 +/- 5% (P < 0.001) of observed capillaries. Stimulation of pancreatic perfusion with intravenous secretin (5 CU/kg/hr) induced a transient decline to 0.94 nl/min (P < 0.05) followed by a continuous increase to 2.39 nl/min (P < 0.001). The intermittent flow pattern was modified in 15 +/- 3% of capillaries (P < 0.05). Fluorescent-labeled erythrocytes provide unique and reliable qualitative and quantitative data about pancreatic microcirculatory changes. Confinement of the fluorescent tracer to erythrocytes prevents extravasation and minimizes phototoxicity, thereby improving intravital analysis of blood flow in pancreatic exchange capillaries.

Animals↗
PubMed1995

Peritoneal host defenses are less impaired by laparoscopy than by open operation.

There is a growing body of evidence that laparoscopic surgery is physiologically less injurious than open surgery. We hypothesized that the open technique results in a greater impairment of peritoneal and systemic defense mechanisms than does the laparoscopic technique. Nissen fundoplication, standardized in technique and duration, was performed in 16 pigs. The procedure was performed through a standard midline incision (OPEN, n = 8) or with laparoscopic technique and CO2 pneumoperitoneum (LAP, n = 8). The peritoneal cavity was instilled with 400 cc of normal saline, either alone (not contamined, n = 8) or containing 10(9) E. coli/ml (contaminated, n = 8). Quantitative cultures, cell count, and flow cytometry were performed on blood and peritoneal fluid samples obtained at timed intervals. We found that host defense processes were better preserved after LAP than by OPEN surgery. Peritoneal and systemic monocyte class II antigen expression, and serum tumor necrosis factor-alpha activity was greater in the OPEN group compared with the LAP group, but peritoneal bacterial clearance was more efficient in the LAP group. These data may illustrate a potential benefit of laparoscopic surgery in cases of peritoneal contamination.

Animals↗
PubMed1995

Effect of microcirculatory perfusion on distribution of trypsinogen activation peptides in acute experimental pancreatitis.

Extraintestinal trypsinogen activation peptides (TAP) have been shown to correlate with severity of acute pancreatitis in humans as well as in various animal models. Ischemia superimposed on experimental pancreatitis, however, increases acinar cell injury without increasing TAP in plasma. We speculated that TAP generated in the pancreas might not reach the circulation in necrotizing pancreatitis due to decreased pancreatic perfusion. To test the hypothesis that generation of TAP in plasma is related to pancreatic perfusion and that plasma TAP may therefore underestimate acinar cell injury in necrotizing disease, we correlated TAP in pancreatic tissue and body fluids with capillary pancreatic blood flow in necrotizing and edematous pancreatitis. The ratio between necrosis and TAP in tissue was similar in both models; the ratio between TAP in plasma and tissue, however, was significantly lower in necrotizing pancreatitis, indicating that a certain amount of TAP generated in the pancreas did not reach the circulation. Decreased pancreatic perfusion found in necrotizing pancreatitis was consistent with this finding. Our data suggest that TAP in tissue is most reliable to indicate severity of acute pancreatitis, whereas plasma TAP may underestimate pancreatic injury in necrotizing disease due to decreased pancreatic perfusion.

Acute Disease↗
PubMed1995

Isovolemic hemodilution with dextran prevents contrast medium induced impairment of pancreatic microcirculation in necrotizing pancreatitis of the rat.

BACKGROUND: Previous studies demonstrated that intravenous contrast medium (CM), as used in contrast enhanced computed tomography, aggravates the impairment of pancreatic microcirculation (PM) characteristic of severe pancreatitis and increases necrosis and mortality in necrotizing pancreatitis (NP) in rats. This study evaluates the use of isovolemic hemodilution, which can enhance the microcirculation in severe pancreatitis, for preventing CM-induced injury. METHODS: NP was induced in 30 dextran-tolerant Wistar rats by intraductal glycodeoxycholic acid and intravenous cerulein for 6 hours. PM was quantified by intravital microscopy using fluorescein isothiocyanate labeled erythrocytes. Based on previous results, areas with low blood flow (< 1.6 nL/min/cap) were identified and baseline recordings of capillary blood flow taken. A reduction of hematocrit to 75% of baseline was achieved by replacement of 5 mL/kg of blood with 25 mL/kg Ringer's lactate (RL) or by exchange of 8 mL/kg of blood for the same amount of dextran 70.6%. Thereafter, the nonionic CM iopamidol (Solutrast, Byk Gulden, Konstanz, Germany) was injected during 1 minute and PM measurements repeated after 30 and 60 minutes. RESULTS: Despite hemodilution with RL, pancreatic capillary perfusion was significantly decreased to 87% of baseline (0.83 +/- 0.04 mL/min/cap; n = 216) 60 minutes after CM infusion (P < 0.05). In contrast, capillary blood flow was significantly increased to 161% (1.56 +/- 0.05 nL/min/cap; n = 278) in the group treated with dextran. Moreover, the percentage of capillaries developing complete stasis was significantly lower in the dextran group (2.3 +/- 1.2%) compared to animals diluted with RL (22.3 +/- 4.8%) (P < 0.002). CONCLUSION: Isovolemic hemodilution with dextran prevents the additional impairment of pancreatic microcirculation induced by CM in NP.

Acute Disease↗
PubMed1995

Intravenous contrast medium aggravates the impairment of pancreatic microcirculation in necrotizing pancreatitis in the rat.

BACKGROUND: Previous reports demonstrated that radiographic contrast medium, as used in contrast-enhanced computed tomography, increases acinar necrosis and mortality in experimental pancreatitis. The authors studied the possibility that these changes may be related to an additional impairment of pancreatic microcirculation. METHODS: Fifty Wistar rats had acute pancreatitis induced by intraductal glycodeoxycholic acid (10 mmol/L for 10 min) and intravenous cerulein (5 micrograms/kg/hr for 6 hrs). After rehydration (16 mL/kg), pancreatic capillary perfusion was quantified by means of intravital microscopy at baseline before intravenous infusion of contrast medium (n = 25) or saline (n = 25), and 30 and 60 minutes thereafter. In addition to total capillary flow, capillaries were categorized as high- or low-flow (> or < 1.6 nL/min). RESULTS: Pancreatic capillary flow did not change in either high- or low-flow capillaries after saline infusion. However, contrast medium infusion induced a significant decrease of total capillary flow (p < 0.001). Analysis according to the relative flow rate revealed that this was primarily because of a significant additional reduction of perfusion in low-flow capillaries (p < 0.0001). Furthermore, complete capillary stasis was observed in 15.9 +/- 3.4% after contrast medium as compared with 3.2 +/- 1.2% after saline infusion (p < 0.006). CONCLUSION: Radiographic contrast medium aggravates the impairment of pancreatic microcirculation in experimental necrotizing pancreatitis.

Acute Disease↗
PubMed1995

Hyperoncotic dextran and systemic aprotinin in necrotizing rodent pancreatitis.

BACKGROUND: Dextrans improve pancreatic microcirculation in acute experimental pancreatitis. They could therefore facilitate the transport of a protease inhibitor to ischemic areas of tissue injury and be of additional benefit. METHODS: To compare the effects of dextrans with and without aprotinin, necrotizing pancreatitis was induced in 33 male dextran-resistant Wistar rats by intraductal infusion of low-dose glycodeoxycholic acid (10 mmol/l) followed by intravenous cerulein (5 micrograms/kg/h) for 6 h. Three and four hours after the start of the cerulein infusion the animals received infusions of either Ringer's lactate (RL) (12 ml/kg), 70,000 Da dextran (10%) (DEX-70) (4 ml/kg) alone, or DEX-70 (4 ml/kg) with aprotinin (5000 IU/kg) (DEX-70/A). RESULTS: The death rate was 60% within 9 h in the RL group (6 of 10) but only 10% in the DEX-70 group (1 of 10) (p < 0.03; Fisher's exact test) and 23% in the DEX-70/A group (3 of 13). Histomorphometry demonstrated a significant reduction of acinar necrosis in both treatment groups compared with control animals (p < 0.014; t test). Total amounts of trypsinogen activation peptides (TAP) in ascites were also significantly lower in these groups (p < 0.05; t test). CONCLUSIONS: DEX-70 given 3 h and 4 h after induction of pancreatitis significantly reduced the levels of TAP, limited acinar necrosis, and improved survival rate in acute necrotizing rodent pancreatitis. There was no additional benefit from the combination with aprotinin.

Acute Disease↗