Search PubMed⌕ Search

Biomedical subjects

E Klar

Publications and source records attributed to E Klar.

At least 19 recordsLinked to original sources
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

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

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

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↗
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↗
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↗
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↗
PubMed1990

Pancreatic ischaemia in experimental acute pancreatitis: mechanism, significance and therapy.

Much clinical and experimental evidence suggests that pancreatic ischaemia in the early phase of acute pancreatitis is important in the development of pancreatic necrosis. While depletion of intravascular volume has often been assumed to be the main circulatory defect, an additional disturbance of pancreatic microcirculation has been demonstrated experimentally. Possible contributory mechanisms include chemical-induced vasoconstriction, direct injury of vessel wall, intravascular coagulation and increased endothelial permeability resulting in pancreatic oedema, haemoconcentration and impaired venous drainage. Pancreatic ischaemia as a consequence of these local effects seems to be responsible for the transition of mild pancreatitis to parenchymal necrosis. In experimental models the beneficial effect of various drugs and of sympathetic blockade has been ascribed to an improvement in pancreatic perfusion. Although effective volume therapy is generally accepted as the mainstay of conservative treatment in acute pancreatitis, the efficacy of different fluid preparations is still controversial, and simple fluid resuscitation has not been shown to prevent the development of parenchymal necrosis. The specific impairment of pancreatic microcirculation cannot be prevented merely by replenishment of intravascular volume with crystalloids, albumin or plasma despite normalization of macrohaemodynamics. In contrast, partial replacement of blood by dextran preparations has been shown to increase pancreatic perfusion by improving blood fluidity. Isovolaemic haemodilution in conjunction with conventional fluid therapy may provide a new and effective means of protecting the pancreas from secondary injury due to the early ischaemic phase of acute pancreatitis.

Acute Disease↗