Biomedical subjects

H G Hotz

Publications and source records attributed to H G Hotz.

At least 19 recordsLinked to original sources

PubMed2001

An improved clinical model of orthotopic pancreatic cancer in immunocompetent Lewis rats.

The study of pancreatic cancer (PaCa) requires orthotopic, clinically relevant animal models. The aims of this study were to establish an orthotopic model of ductal pancreatic adenocarcinoma in immunocompetent Lewis rats and to develop a scoring system to quantify local tumor infiltration and distant metastasis. Cells (10(7)) of the rat ductal PaCa cell line DSL-6A/C1 were injected s.c. into donor rats. After 8 weeks, either three (IPL-3) or five (IPL-5) fragments (1 mm3) of the resulting s.c. tumors were microsurgically implanted into the pancreas of recipient rats. In another series of animals, 10(7) DSL-6A/C1 cells were directly injected (INJ) into the pancreas. All animals were monitored daily until death or for 16 weeks. At autopsy, volume of primary tumors and ascites, local and systemic tumor spread, and histologic phenotype were assessed. IPL-5 resulted in significantly larger tumors (12,224 +/- 1,933 mm3), more local infiltration and systemic spread (score: 18.3 +/- 2.0 points), severe clinical tumor disease, and lethality (50%) in comparison to the other induction techniques (IPL-3: 283 +/- 115 mm3/3.5 +/- 0.8 points/0; INJ: 752 +/- 207 mm3/4.3 +/- 0.8 points/8%). Histologic examination revealed moderately to well-differentiated ductal tumors, surrounded by dense stroma. Intraperitoneal tumor dissemination in the INJ group occurred simultaneous with primary tumor growth, indicating PaCa cell spread during injection. Orthotopic implantation of five DSL-6A/C1 tumor fragments into the rat pancreas provides a valid clinical model of ductal pancreatic adenocarcinoma in immunocompetent rodents for preclinical treatment studies. The dissemination score we used permitted quantification of local and systemic tumor spread.

Adenocarcinoma↗

PubMed2001

Endothelin mediates local and systemic disease sequelae in severe experimental pancreatitis.

Endothelin-1 has been shown to reduce pancreatic blood flow and cause focal acinar cell necrosis similar to those seen in acute pancreatitis (AP), whereas therapy with endothelin receptor antagonists enhanced pancreatic capillary blood flow (PCBF) and decreased mortality rates. The current study evaluated the role of endothelin in the development of severe AP. Trypsinogen activation peptides, acinar cell necrosis, and PCBF were used as local indicators of disease severity, fluid sequestration, cardiorespiratory and renal parameters, and colonic capillary blood flow as systemic disease indicators. The following groups of animals were examined: 1) rats with mild edematous AP and 2) severe necrotizing AP treated with and without endothelin, 3) transgenic rats overexpressing endothelin with severe AP, and 4) rats with severe AP prophylactically treated with endothelin receptor antagonists. The following observations were made: endothelin superimposed on mild AP caused hemoconcentration, a decrease in PCBF, and necrosis and ascites not seen in this model without endothelin exposure. Endothelin superimposed on severe AP had no significant effects. After induction of severe AP, less PCBF and more acinar cell necrosis were observed in transgenic rats than in their normal littermates. Prophylactic endothelin receptor antagonists improved local (acinar necrosis, PCBF) and systemic parameters (ascites, urine production, colonic capillary blood flow) of disease severity in animals with severe AP. These observations underscore the role of endothelin as a mediator of disease severity in AP and suggest that endothelin receptor blockade may become a promising therapeutic tool in this disease.

Acute Disease↗

PubMed2000

Experimental models of acute pancreatitis: are they suitable for evaluating therapy?

Since randomized controlled studies of severe acute human pancreatitis can be performed only with restrictions, at least some aspects of innovative therapy concepts should first be clarified in animal experiments. In vitro trials are inadequate for this purpose since they cannot simulate the complex course of severe acute pancreatitis. Animal test results can be transferred to clinical practice if the results are based on trials with established models, standardized methods, and a study design imitating the clinical situation. This contribution discusses the demands on such an animal model of acute pancreatitis and a corresponding study protocol and presents models and protocols which meet these requirements. Concrete examples are presented to show that animal experiments are of great value under these conditions, especially in acute necrotizing pancreatitis. Further standardization of models, protocols, and monitoring should further improve future animal therapy studies at least to the extent that it is possible to select particularly promising substances, which should then be tested in randomized controlled trials.

Acute Disease↗

PubMed2000

Animal models of exocrine pancreatic cancer.

Clinically and biologically relevant animal models are mandatory to further evaluate both the pathophysiology and novel strategies for diagnosis and treatment of exocrine pancreatic cancer. This review briefly summarizes the features of human pancreatic cancer in order to define requirements for animal models of the disease. The described model systems in rodents include pancreatic cancer induced by chemicals, pancreatic cancer in transgenic, and immunodeficient animals.

Animals↗

PubMed2000

Endothelin receptor blockade in severe acute pancreatitis leads to systemic enhancement of microcirculation, stabilization of capillary permeability, and improved survival rates.

BACKGROUND: We previously demonstrated that therapy with a new endothelin A receptor antagonist (ET-RA) significantly reduced mortality rates in severe acute pancreatitis (AP) in the rat without attenuating local signs of disease severity (intrapancreatic protease activation, acinar cell necrosis). This raised the question as to why ET-RA was so effective. The purpose of this study was to assess the effect of ET-RA on microcirculation (particularly capillary permeability) within and outside of the pancreas on intravascular fluid loss and extravascular fluid sequestration and on distant organ function. METHODS: Severe AP was induced in rats by standardized intraductal bile acid infusion and cerulein hyper-stimulation. Starting 6 hours (n = 24 rats) and 12 hours (n = 30 rats) after the onset of AP, animals randomly received either the ET-RA (LU-135252) or saline solution with fluid resuscitation (6 mL/kg/h Ringer's lactate). At 24 hours, animals were relaparotomized for intravital microscopic determination of capillary blood flow, leukocyte rolling, and capillary permeability in the pancreas and colon. Further monitoring included cardiorespiratory and renal parameters, hematocrit levels and quantification of ascites and pleural effusions, and acinar cell necrosis at autopsy. Groups of sham-operated healthy animals (n = 6 animals each) that had been treated according to the same protocol served as control animals. RESULTS: ET-RA treatment that was started 6 hours after AP-induction significantly decreased hematocrit levels (38% +/- 1% vs 45% +/- 2% with saline solution treatment), reduced ascites and pleural effusions (6.7 +/- 1.3 mL vs 11.9 +/- 1.3 mL), and improved urine production (4.8 +/- 0.5 mL vs 2.9 +/- 0.6 mL) and respiratory parameters. Moreover, all microcirculatory parameters were improved; in particular, capillary permeability was stabilized (158% +/- 9% vs 248% +/- 8% in the colon). These beneficial effects were also seen when therapy was delayed until 12 hours after AP induction. Pancreatic necrosis was not significantly reduced. The overall mortality rate was 12% in ET-RA-treated animals and 42% in saline solution-treated control animals (P <.05). In healthy animals ET-RA did not significantly alter the target parameters, except for a reduction of capillary permeability in the pancreas. CONCLUSIONS: Improved microcirculation and stabilized capillary permeability in ET-RA-treated animals together with reduced intravascular fluid loss and extravascular fluid sequestration and improved renal and pulmonary function (1) may explain improved survival in this model, (2) support the hypothesis that systemic disease sequelae significantly contribute to outcome in AP, and (3) suggest that ET-RA may be a promising therapeutic tool in AP because it counteracts microcirculatory disorders that contribute to pancreatitis-associated organ dysfunction even when therapy is delayed to a point at which pancreatic injury may no longer be influenced.

Acute Disease↗

PubMed2000

Effect of endothelin and endothelin receptor blockade on capillary permeability in experimental pancreatitis.

BACKGROUND: Capillary leakage with fluid loss into the third space contributes to many of the early systemic complications in severe acute pancreatitis. There has been increasing interest in endothelin as one of the factors affecting capillary permeability. AIM: To elucidate further the role of endothelin in the development of capillary leakage in acute pancreatitis by investigating the effect of exogenous endothelin administration and endothelin receptor blockade in sham operated animals and two models of acute pancreatitis. METHODS: Determination of capillary permeability in the pancreas and colonic mucosa by quantifying extravasation of fluorescein labelled dextran using a novel computer assisted video image analysis system. RESULTS: Pancreatic and colonic capillary permeability increased stepwise from mild to severe acute pancreatitis. Endothelin increased pancreatic and colonic capillary permeability in healthy animals and animals with mild acute pancreatitis but had no additional adverse effect in severe acute pancreatitis. Endothelin receptor blockade decreased pancreatic capillary permeability in sham operated rats but had no effect on the colon. In mild and severe acute pancreatitis, endothelin receptor blockade stabilised increased capillary permeability in both the pancreas and colon. CONCLUSIONS: Endothelin plays an important role in mediating capillary permeability in the pancreas. In severe pancreatitis, it increases capillary permeability even outside the pancreas, thereby contributing to capillary leakage. Endothelin receptor blockade significantly reduces capillary permeability in acute pancreatitis both in and outside the pancreas, suggesting a therapeutic approach to counteract capillary leakage in severe acute pancreatitis.

Animals↗

PubMed1999

Does glutamine reduce bacterial translocation? A study in two animal models with impaired gut barrier.

Failure of intestinal barrier function and subsequent translocation of bacteria from the gut are believed to play a decisive role in the development of systemic septic complications, for example, following major trauma or major abdominal surgery. This study evaluated: (a) the effect of glutamine on colonic microcirculation and electrophysiological parameters reflecting gut barrier function, (b) the translocation of live bacteria to extraintestinal organs, and (c) disease outcome in two animal models with impaired gut barrier function. Severe acute pancreatitis or colitis was induced in rats randomized for therapy with or without glutamine (0.5 g/kg daily). After 48 h one animal group was prepared for intravital microscopy of colonic capillary blood flow and electrophysiological measurement of gut permeability; another was killed after 96 h for histological and microbiological examination. In animals with pancreatitis, glutamine (Gln) supplementation significantly improved gut permeability, i.e., Gln increased colonic transmucosal resistance from 67+/-7 to 92+/-3 Omega/cm(2) and decreased mannitol flux through the epithelium by 53%. Capillary blood flow in the colonic mucosa was improved by 25%. The prevalence of pancreatic infections was reduced from 86% in animals on standard parenteral nutrition to 33% in animals given the Gln-enriched diet (P<0.05); mortality decreased by 32%. In colitis, Gln had no significant effect on these parameters except for improving colonic capillary blood flow in colon segments not adjacent to the major injury site. Glutamine supplementation improves colonic capillary blood flow, stabilizes gut permeability, and reduces secondary pancreatic infections and mortality in severe rodent pancreatitis, but it is not helpful in colitis. This confirms previous reports that glutamine stabilizes gut barrier function only in certain diseases. Our experimental data strongly suggest that acute pancreatitis (rather than colitis) is one of the diseases with gut barrier dysfunction in which glutamine substitution may be helpful to reduce bacterial translocation and should therefore be tested in a controlled clinical trial.

Animals↗

PubMed1999

Systemic lymphocyte activation modulates the severity of diet-induced acute pancreatitis in mice.

To examine the role of lymphocyte activation in the development of local and systemic complications in acute pancreatitis, we compared disease severity of choline-deficient, 0.5% ethionine supplemented (CDE) diet-induced acute pancreatitis in T- and B-cell deficient SCID mice and immunocompetent C.B-17 mice. Twenty-five female SCID and 17 female C.B-17 mice were fasted for 24 h and fed a CDE diet for 72 h. Twenty SCID and 12 C.B-17 mice were bled and their organs removed for histologic evaluation. Five control animals of both kinds were fed a regular diet for 6 days. Lung, kidney, and pancreas were examined microscopically, and pancreatic damage scored. Apoptosis was detected by DNA nick-end labeling and confirmed by DNA laddering. Trypsinogen-activation peptide was measured by enzyme-linked immunosorbent assay (ELISA), and the catalytic activity of PLA2 was determined by a radiometric assay. Four-day mortality was 10% in SCID and 33% in C.B-17 mice, and 10-day mortality was 0 in SCID and 60% in C.B-17 mice. SCID mice had mild pulmonary damage, whereas pulmonary injury was severe in C.B-17 mice. Pancreatic damage was severe in both groups. Even though in situ staining of apoptotic cells was found in all pancreatitis animals, apoptosis was confirmed by DNA laddering only in C.B-17 mice. In SCID mice, apoptotic cell staining positively correlated with necrosis (r = 0.91; p < 0.001). Plasma TAP and PLA2 catalytic activity did not differ significantly between the groups. In conclusion, the absence of T and B lymphocytes prevents severe pulmonary injury resulting from acute pancreatitis but does not influence pancreatic or renal damage. Our results suggest that systemic lymphocyte activation does not affect the initiating events that trigger pancreatic injury but modulates the systemic response, in particular, pulmonary injury caused by acute pancreatitis.

Acute Disease↗

PubMed1998

Prophylactic thyroidectomy in MEN IIA: does the calcitonin level correlate with tumor spread?

BACKGROUND: The fate of patients with multiple endocrine neoplasia of type II A (MEN II A) is determined by medullary thyroid carcinoma, which occurs in all cases. This has led to the therapeutic concept of prophylactic thyroidectomy in affected family members with the goal of removing the thyroid before the manifestation of carcinoma. We investigated a prophylactically thyroidectomized MEN II A population to determine whether the highly specific and sensitive tumor marker calcitonin correlates with tumor spread. PATIENTS AND METHODS: Fifteen patients with MEN II A (aged 4-24 years) who had undergone prophylactic thyroidectomy since 1990 were included in the study. Baseline and pentagastrin-stimulated calcitonin levels were preoperatively determined in all cases. The indication for surgery was established on the basis of pathologic calcitonin levels in the first seven patients and on the basis of detected RET proto-oncogene mutation in the other eight patients. Bilateral central lymphadenectomy was performed in all patients in addition to thyroidectomy. RESULTS: Histology demonstrated C-cell hyperplasia in five patients (aged 4-13 years), unilateral medullary microcarcinoma in six (aged 9-17 years) and a bilateral medullary microcarcinoma in three cases (aged 17-24 years). One 9-year-old boy with bilateral microcarcinoma already had a lymph node metastasis. The mean baseline calcitonin level correlated with the histologic findings (r=0.71, P=0.003) but there was no correlation between pentagastrin-stimulated calcitonin levels and histology (r=0.21, P=0.47). CONCLUSION: In MEN II A patients undergoing prophylactic thyroidectomy, baseline but not stimulated calcitonin levels already correlate with the histologic tumor stage at the stage of clinically occult C-cell hyperplasia or medullary microcarcinoma. However, biochemical screening cannot reliably discriminate the transition from C-cell hyperplasia to invasive microcarcinoma. Individuals with MEN IIA should therefore undergo early prophylactic thyroidectomy once the diagnosis is confirmed by molecular genetic testing.

Adolescent↗

PubMed1998

Endothelin receptor blockade improves fluid sequestration, pancreatic capillary blood flow, and survival in severe experimental pancreatitis.

OBJECTIVE: To evaluate the effect of a new endothelin receptor antagonist (ET-RA) on the course of severe experimental pancreatitis. BACKGROUND: Endothelin-1 has been shown to reduce regional blood flow in various organs, including the pancreas, and to aggravate cerulein-induced mild pancreatitis. METHODS: Acute necrotizing pancreatitis (ANP) was induced in rats by standardized intraductal bile acid infusion and cerulein hyperstimulation. Serum trypsinogen activation peptides (TAP) were measured to verify comparable disease severity. Starting 6 hours after the onset of ANP, animals randomly received either saline or the new ET-RA LU-135252. Monitoring included cardiorespiratory parameters, urine output, hematocrit, and TAP levels. After 24 hours, animals were relaparotomized to determine pancreatic capillary blood flow and to assess the amount of free intraabdominal fluid and acinar cell necrosis. Survival was determined in a second set of experiments on 24 animals observed for 48 hours after pancreatitis induction and treatment with either normal saline or ET-RA. RESULTS: Comparable TAP increases confirmed equally severe ANP in both groups before treatment. Treatment with ET-RA significantly reduced the mortality rate, from 50% in untreated animals to 8%. Improved survival was associated with significantly decreased hematocrit, improved urinary output, decreased ascites, and increased pancreatic capillary blood flow. There were no significant differences in plasma TAP and acinar cell injury in the surviving animals of the two treatment groups. CONCLUSION: Therapy with the new ET-RA reduces the early mortality rate in experimental ANP, probably by reducing fluid sequestration and improving microcirculation.

Acute Disease↗

PubMed1997

Influence of changes in pancreatic tissue morphology and capillary blood flow on antibiotic tissue concentrations in the pancreas during the progression of acute pancreatitis.

BACKGROUND: The ability of an antibiotic to reach bactericidal concentrations in tissue depends on numerous factors including tissue composition and regional perfusion. Although necrotising pancreatitis is characterised by progression of pancreatic necrosis over at least 96 hours and microcirculatory alterations, the impact of these changes on the concentration of antibiotics in the pancreas has not yet been investigated. AIM: To determine and compare pancreatic tissue concentrations of imipenem and cefotaxime at different stages of acute necrotising pancreatitis in an animal model that has been shown to mimic closely the pathomorphological and bacteriological features of severe human pancreatitis. METHOD: Acute necrotising pancreatitis was induced in rats by a standardised intraductal infusion of glycodeoxycholic acid and intravenous cerulein. Six hours (n = 16) and 48 hours (n = 16) after induction of pancreatitis, the animals were randomised for intravenous therapy with either imipenem or cefotaxime. Fifteen minutes after injection of the antibiotic, the animals were killed. Blood and the head of the pancreas were collected for determining imipenem or cefotaxime in serum and tissue; the splenic portion of the pancreas was prepared for histological examination. In an additional set of identically treated animals, pancreatic capillary blood flow (PCBF) was assessed by intravital microscopy before induction of acute necrotising pancreatitis and at the time of antibiotic therapy. RESULTS: Imipenem accumulates in the pancreas in the initial phase of acute necrotising pancreatitis characterised by pronounced oedema and decreased PCBF, and tends to decrease with resolution of the oedema and the progression of acinar cell necrosis in the later course of the disease. Concentrations of cefotaxime are low in oedematous pancreatic tissue early after induction of acute necrotising pancreatitis and increase with the resolution of oedema and normalisation of PCBF. CONCLUSIONS: Concentrations of antibiotics in the pancreas vary in acute necrotising pancreatitis, depending on changes in pancreatic tissue morphology and capillary blood flow. This suggests that antibiotic tissue concentrations may not be consistent from one agent to another and that efficacy of antibiotics in acute pancreatitis cannot be estimated solely on the basis of their pharmacological and microbiological properties.

Acute Disease↗

PubMed1997

[Between bench and bedside: examples of clinically oriented basic surgery research].

Animal experimental studies are an effective modality for testing new therapeutic strategies, provided that the animal model and the study protocol simulate the clinical situation. This is exemplified by various animal experimental studies on the therapy of infectious complications in acute necrotizing pancreatitis that were performed preliminary or supplementary to clinical studies. The results show that basic surgical research with close clinical orientation can be usefully and fruitfully combined with clinical studies and enables the academically active young surgeon to overcome the dualism between laboratory work and clinical practice.

Animals↗

PubMed1997

[Is preoperative scintigraphy in euthyroid nodular goiter necessary?].

Preoperative thyroid isotope scan would influence the operative procedure and the perioperative management in patients with nontoxic goiter only if it raises suspicion of malignancy. However, the scintigram shows significantly lower sensitivity and specificity in the detection and prediction of malignant nodules in the thyroid gland than the ultrasound examination. Thyroid isotope scan is more expensive than ultrasonography, and its routine use in the investigation of nontoxic nodular goiter should be abandoned.

Cost-Benefit Analysis↗

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↗

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↗