Reducing the risk of dislocation after total hip arthroplasty: the effect of orientation of the acetabular component.

Malposition of the acetabular component is a risk factor for post-operative dislocation after total hip replacement (THR). We have investigated the influence of the orientation of the acetabular component on the probability of dislocation. Radiological anteversion and abduction of the component of 127 hips which dislocated post-operatively were measured by Einzel-Bild-Röentgen-Analysis and compared with those in a control group of 342 patients. In the control group, the mean value of anteversion was 15 degrees and of abduction 44 degrees. Patients with anterior dislocation after primary THR showed significant differences in the mean angle of anteversion (17 degrees), and abduction (48 degrees) as did patients with posterior dislocation (anteversion 11 degrees, abduction 42 degrees). After revision patients with posterior dislocation showed significant differences in anteversion (12 degrees) and abduction (40 degrees). Our results demonstrate the importance of accurate positioning of the acetabular component in order to reduce the frequency of subsequent dislocations. Radiological anteversion of 15 degrees and abduction of 45 degrees are the lowest at-risk values for dislocation.

Asymmetric termination of secondarily generalized tonic-clonic seizures in temporal lobe epilepsy.

In patients with secondarily generalized tonic-clonic seizures (sGTCS) an asymmetric termination of the clonic phase can be observed. The authors systematically analyzed this phenomenon in patients with temporal lobe epilepsy (TLE). Thirty-nine sGTCS from 29 patients with TLE who underwent successful epilepsy surgery were analyzed, in addition to a prospectively collected group of 28 patients with TLE who had 35 sGTCS. The clonic phase of sGTCS did not end synchronously in 65.7% of all patients and in 59.4% of all seizures. In 79.3% to 80% this was ipsilateral to the hemisphere of seizure onset, and there was excellent interobserver agreement.

Plasma levels of cardiac troponin I after prolonged strenuous endurance exercise.

This study provides biochemical evidence that ultraendurance exercise may cause subclinical myocardial damage, even in well-trained cyclists. The cellular nature of this damage and its clinical relevance remain unknown at present.

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.

Therapy for microcirculatory disorders in severe acute pancreatitis: comparison of delayed therapy with ICAM-1 antibodies and a specific endothelin A receptor antagonist.

Many of the complications in severe acute pancreatitis result from the amplifying effects of microcirculatory disruption. The pathogenesis of these microcirculatory disorders is multifactorial and involves various vasoactive mediators. Thus questions arise as to which vasoactive mediators are most important and how long after the onset of disease vasoactive mediator blockade may be effective. The present study compares the effect of delayed therapy with two vasoactive mediator antagonists, previously tested with promising results in other studies in a well-established rodent model of severe acute pancreatitis. Twelve hours after induction of acute pancreatitis, rats were randomized to therapy with intracellular adhesion molecule-1 (ICAM-1) antibody (2 mg/kg IA-29), endothelin A receptor antagonist (ET-RA) (40 mg/kg LU 135252), or saline solution (volume equivalent). After 12 hours of fluid resuscitation, animals underwent repeat laparotomy for intravital microscopic determination of capillary blood flow, leukocyte rolling, and capillary permeability in the pancreas and colon. Other measurements included cardiorespiratory parameters, hematocrit, pleural effusions, ascites, urine production, and survival. Compared to saline treatment, both ICAM antibody and ET-RA significantly enhanced capillary blood flow in the pancreas and colon, reduced leukocyte rolling, and stabilized capillary permeability. These beneficial effects on microcirculation were associated with decreased fluid loss into the third space and improved renal function and survival. Although both antagonists likewise enhanced capillary blood flow and reduced leukocyte rolling, ET-RA was significantly more effective than ICAM antibody in counteracting capillary leakage, thereby further reducing fluid sequestration. The present study confirms the beneficial effects of endothelin and ICAM antagonists in severe acute pancreatitis, even with delayed therapy, suggesting that both compounds are candidates for further clinical testing. Selective endothelin A receptor blockade appears to be especially attractive for clinical use not only because it was superior to ICAM antibody in the present study but also because of its favorable pharmacologic properties and (preliminary) positive results in clinical phase 2 studies currently underway for other diseases.

Therapy for microcirculatory disorders in severe acute pancreatitis: effectiveness of platelet-activating factor receptor blockade vs. endothelin receptor blockade.

Many of the complications of severe acute pancreatitis are the result of the amplifying effects of microcirculatory disruption. The factors causing microcirculatory disorders in acute pancreatitis involve vasoactive mediators such as platelet-activating factor (PAF) and endothelin-1 (ET) activated during the inflammatory response to pancreatic injury. To further evaluate the potential therapeutic role of specific receptor antagonists (RA) to these mediators, the present study compares the effect of PAF and ET receptor blockade on microcirculation and organ function in a well-established rodent model of severe acute pancreatitis. Six hours after acute pancreatitis induction, rats were randomized to therapy with ET-RA (50 mg/kg LU-135252), PAF-RA (82 microg/kg WEB-2170), or NaCl 0.9% (volume equivalent). After 18 hours of fluid resuscitation, animals were relaparotomized for intravital microscopic determination of capillary blood flow, leukocyte rolling, and capillary permeability in the pancreas and colon. Other measurements included cardiorespiratory parameters, hematocrit, pleural effusions, ascites, urine production, and survival. Compared to saline treatment both ET-RA and PAF-RA significantly improved capillary blood flow in the pancreas and colon, reduced leukocyte rolling, and stabilized capillary permeability. The beneficial effects of receptor antagonist treatment on microcirculation were associated with decreased fluid loss into the third space, improved renal and respiratory function, and survival. Although both receptor antagonists likewise improved capillary blood flow, ET-RA was significantly more effective in counteracting leukocyte rolling and capillary leakage, thereby further reducing fluid sequestration. The present study confirms the beneficial effects of PAf and ET receptor blockade on microcirculation inside and outside the pancreas, organ function, and survival when given at the early stage of severe pancreatitis. Because ET-RA was more effective in stabilizing capillary permeability and avoiding subsequent fluid loss into the third space, we propose that ET-RA should be tested in a clinical trial (either in comparison or in addition to PAF-RA).

Increased frequency of thorax injuries with ACD-CPR.

A prospective, randomised out-of-hospital study in a two-tiered system with active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) versus standard (STD) CPR in patients following non-traumatic cardiac arrest was planned to test the hypothesis that ACD-CPR by the first tier may increase the occurrence of ventricular fibrillation as compared with STD-CPR. Furthermore, in a later phase of the study, sternal and rib fractures induced by both CPR methods were determined by extensive autopsy. After enrolling 90 patients the study was terminated because of a high frequency of chest injuries found at autopsy. Forty-two patients received STD-CPR from the first tier and ACD-CPR from the second tier. Thirty-three patients received ACD-CPR only by the first and the second tier, while 15 patients received STD-CPR only from the first and second tiers. In order to obtain a sufficiently large control group for autopsy findings after STD-CPR, STD-CPR was performed in an additional 33 patients within a second period of 4 months. There was no improvement in the number of patients found in ventricular fibrillation after ACD-CPR as compared to STD-CPR performed by the first tier. In patients undergoing autopsy (n = 35) there were significantly more sternal fractures with ACD-CPR versus STD-CPR (14/15 vs. 6/20; P <0.005) and rib fractures (13/15 vs. 11/20; P < 0.05) In conclusion, ACD-CPR appears to cause more CPR-related injuries than does standard CPR, but as a result of a number of limitations on this study, this fact cannot be proven beyond doubt.

Contrast-enhanced transrectal color doppler ultrasonography (TRCDUS) for assessment of angiogenesis in prostate cancer.

BACKGROUND: The clinical relevance of tumor angiogenesis has been investigated in several human tumors, including prostate carcinoma (PC). Previously, we found angiogenesis, measured as microvessel density (MVD), to be an independent prognostic factor in PC. Therefore, we evaluated contrast-enhanced Transrectal Color Doppler Ultrasonography (TRCDUS) for assessment of angiogenesis in PC. MATERIALS AND METHODS: We investigated 15 patients with PC before radical prostatectomy (RP) and 3 control patients before radical cystoprostatectomy. TRCDUS was performed using a micro-bubble-based ultrasound enhancer Levovist for identifying hypervascularized areas within the prostate. Computer-assisted quantification of color pixel intensity (PI) was used to evaluate objectively the hypervascularized areas; resistive index (RI) measurements were also obtained in these areas. After histopathological examination of the entire prostate gland for tumor confirmation, immunohistochemical evaluation of MVD using a polyclonal antibody against factor VIII was performed as described by Weidner et al. (N Engl J Med 324: 1-8, 1991). TRCDUS findings were correlated with the immunohistochemical data. RESULTS: All patients showed hypervascularized areas (range: 1-9) on contrast-enhanced TRCDUS. Hypervascularized areas showed a sensitivity of 50.8% and a specificity of 95.2% for detecting PC. Analysis of TRCDUS data and immunohistochemistry revealed a significant correlation between PI and MVD in PC specimens, demonstrating a correlation coefficient of r2 = 0.977 (p<0.001). RI did not correlate with MVD. CONCLUSION: Contrast-enhanced TRCDUS showed a high specificity in identifying PC. PI correlated significantly with MVD. Therefore, quantification of color Doppler signals seems to be helpful for assessment of angiogenesis in PC.

Radiographic abnormalities in the thoracolumbar spine of young elite skiers.

An increased frequency of radiologic abnormalities in the thoracolumbar spine has been reported among young athletes in various sports, but there are no data concerning ski sports. To evaluate the incidence of these abnormalities in young elite skiers, we compared 120 skiers younger than 17 years old (alpine skiers, ski jumpers, and Nordic cross-country skiers) with a random sample of 39 control subjects of the same age who had no history of high-performance sports participation. Standardized anteroposterior and lateral radiographs of the entire lumbar spine, the lower thoracic spine, and the upper part of the sacrum were obtained from each athlete and each control subject. Radiographs were evaluated by two independent observers for the presence and size of anterior and posterior endplate lesions and Schmorl's nodes. The elite alpine skiers and ski jumpers demonstrated a significantly higher rate of anterior endplate lesions than did the control subjects. This finding might be attributable to excessive loading and repetitive trauma of the immature spine under high velocity, especially in the forward bent posture.

Comparison of score evaluations and instrumented measurement after anterior cruciate ligament reconstruction.

Forty-four patients who had undergone unilateral anterior cruciate ligament reconstructions were evaluated retrospectively with seven different scoring systems (International Knee Documentation Committee, Orthopadische Arbeitsgruppe Knie, Lysholm, Feagin and Blake, Zarins and Rowe, Cincinnati, and Marshall scores). The results varied between systems and therefore lacked reliability. Of the 44 patients, 32 were rated as excellent according to the Cincinnati score while only 3 patients were rated as normal according to the International Knee Documentation Committee form. Good and excellent results were found twice as frequently with the Cincinnati and Lysholm scores compared with the scores of Zarins and Rowe or the International Knee Documentation Committee form. Statistical analysis confirmed this observation and revealed significant differences between the scoring systems. Side-to-side differences using the manual maximum displacement test with the KT-1000 arthrometer revealed good correlation with the International Knee Documentation Committee and the Orthopadische Arbeitsgruppe Knie questionnaires. None of the other scoring systems, which do not measure anterior laxity, produced reasonable correlation with instrumented measurements. We found that certain population-specific factors as well as the distribution of single findings can distort the results of scoring systems. To avoid these interference factors, the patient sample should be homogeneous and selected prospectively and there should be agreement about the value of single findings.

RES function and liver microcirculation in the early stage of acute experimental pancreatitis.

BACKGROUND/AIMS: The reticuloendothelial system and in particular the Kupffer cells in the liver are important for eliminating antigens and toxic substances in many diseases including acute pancreatitis. Optimal Kupffer cell function is believed to depend on numerous factors including intact hepatic blood supply and microcirculation. The aim of the study was to evaluate whether hepatic microcirculation and Kupffer cell function are impaired in acute pancreatitis and whether enhancement of hepatic capillary blood flow leads to improved reticuloendothelial system function. METHODOLOGY: Acute pancreatitis was induced in rats by intraductal infusion of bile salt followed by i.v. cerulein hyperstimulation. Animals were randomized to receive either a selective endothelin-A receptor antagonist (ET-RA; LU-135252; 50 mg/kg) or saline. Sham-operated animals (intraductal and i.v. saline infusion) treated according to the same protocol served as controls. Liver phagocytic function was evaluated in 6 animals per group 6 and 24 hrs after acute pancreatitis induction and treatment using 99mTc-labeled Nanocoll and a scintillation camera technique. Another 6 animals of each group were used for intravital microscopic determination of hepatic capillary blood flow using fluorescein-labeled erythrocytes. RESULTS: Six hours after acute pancreatitis induction, hepatic capillary blood flow and nanocoll clearance were significantly decreased in saline-treated animals (compared to saline-treated healthy controls). Endothelin-A receptor antagonist significantly improved hepatic capillary blood flow and nanocoll clearance. This beneficial effect was no longer seen after 24 hrs when these parameters had spontaneously returned to values not significantly different from normal. CONCLUSIONS: Reticuloendothelial system function and hepatic capillary blood flow are impaired (only) in the early stage of this acute pancreatitis model. Endothelin-A receptor antagonist improves hepatic capillary blood flow at this stage. Enhancement of hepatic capillary blood flow is accompanied by normalization of nanocoll clearance, suggesting that hepatic microcirculation influences phagocytic Kupffer cell function early in acute pancreatitis.

[Influence of reflex zone therapy of the feet on intestinal blood flow measured by color Doppler sonography]. / Beeinflussung der Darmdurchblutung durch Fussreflexzonenmassage, gemessen mittels farbkodierter Dopplersonographie.

OBJECTIVE: An influence on organ-associated blood flow is considered as a possible mechanism of action of reflex zone massage of the feet (FRZM) therapy. In the present study we investigated whether changes in intestinal blood flow can be achieved by FRZM. MATERIAL AND METHODS: 32 healthy adults (19 women and 13 men) were randomly assigned to the treatment or the placebo group. Subjects of the treatment group received foot massage on the zones assigned to the intestines and those of the placebo group received massage on zones unrelated to the intestines. Before, during and after FRZM, the blood flow velocity, the peak systolic and the end diastolic velocities in the superior mesenteric artery as well as the resistive index as a parameter of vascular resistance were calculated. RESULTS: During FRZM, in the subjects of the treatment group there was a significant reduction in the resistive index (p = 0.021), suggesting an increase in the blood flow in the superior mesenteric artery and the subordinate vascular system. In contrast, there were no significant changes in the resistive index in the subjects of the placebo group. CONCLUSION: The reduction in the resistive index observed in the treatment group supports the assumption that FRZM improves blood flow in the organs considered to be associated with the specific foot zones, at least during the therapy process.

[Monstrous pseudocyst of the adrenal gland]. / Monströse Pseudocyste der Nebenniere.

We report on a 64-year-old patient with a huge adrenal pseudocyst. These are rare cystic lesions of the adrenal gland with an unclear etiology. Recent studies suggest that the majority of adrenal pseudocysts are of vascular origin. All cystic masses in the epigastric region have to be considered in the differential diagnosis. The treatment of choice is surgical removal.

Evaluation of antimitotic activity of Rotula aquatica (Lour): a traditional herb used in treatment of cancer.

Rotula aquatica was extensively used by vaidyas (Ayurvedic practioners) in holistic treatment of cancer. In the present study, an attempt has been made to evaluate the antimitotic activity of R. aquatica. Preliminary antimitotic screening was done using Allium cepa root tip assay. The mitotic index of the root tips markedly decreased with increasing concentration of the aqueous extract. The different fractions obtained by successive extraction of R. aquatica using solvents of increasing polarity were also evaluated for their antimitotic activity. Tannins were isolated which showed a better activity than the non-tannin fraction. Experiments were also carried out with incorporation of folic acid in the aqueous extract. Folic acid inhibited the antimitotic activity of aqueous extract of R. aquatica in a dose dependent manner. The results obtained were compared with methotrexate--a known drug available in market as anti-cancer agent. The studies were extended to human cells using 3 pancreatic cancer cell lines, viz: HPAF-II, BxPC-3, and CAPAN-2. Extract of R. aquatica was found to be extremely effective in the prevention of cell proliferation of the pancreatic cancer cell lines. The phytochemical evaluation revealed presence of polyphenols (tannins) and steroids. A HPTLC fingerprinting was developed and studied. Two compounds were isolated and subjected to spectral studies like UV, IR and mass spectrums. The empirical formula was derived by considering this data with elemental analysis of the compounds.

[The evaluation of the second-look operation of patients with ovarian carcinoma and tubal carcinoma by means of a retrospective comparison study]. / Die Wertigkeit der Second-Look-Operation bei Patientinnen mit einem Ovarialkarzinom oder Tubenkarzinom mittels einer retrospektiven Vergleichsstudie.

INTRODUCTION: This investigation is a retrospective analysis to evaluate the influence of second-look surgery on the relapse-free and overall survival of patients with ovarian and tubal carcinomas. METHOD: For 208 patients with and without second-look operation out of 469 of the total collective, a matched analysis and a Cox regression model were established in the framework of a multivariate analysis. RESULTS: Second-look surgery in patients with ovarian cancer had no significant influence on the relapse-free and overall survival. The 10-year survival was equal in both groups: CONCLUSION: Second-look surgery cannot be justified on the basis of clinically noninvasive methods such as radiological findings with additional use of tumor markers. It should only be done in control clinical trials to evaluate new means of treatment.

[The effect of the lactation period on the cell content of sheep milk]. / Einfluss der Laktationsperiode auf den Zellgehalt von Schafmilch.

Milk samples of 201 ewes were examined in 6 week intervals during a complete lactation period. Those samples were analyzed for the presence of pathogenic bacteria and the somatic cell count was determined. Besides, the California Mastitis Test (CMT) was performed and the udder was clinically examined. The cell counts were found to depend on the lactation period. During 6 weeks following parturition the cell count was 63,000 cells/ml. This number decreased towards the 24th week of lactation to 32,000 cells/ml. At the end of lactation this value increased again to 425,000 cells/ml. The median value of ewes with normal udder health was 56,000 cells/ml milk. For samples from which pathogenic bacteria were isolated this value was 159,000 cells/ml. The most frequent pathogens isolated from the milk samples were coagulase-negative cocci (59.6% of bacteriologically positive samples), the median number being 88,000 somatic cells/ml in these sheep. Coagulase-positive cocci were isolated in 25.3% of the samples, the median value of the cell count was 295,000 cells/ml. In 12.1% of the samples streptococci were found. The median value was 167,000 cells/ml. From the remaining 3.0% of bacteriologically positive samples Pasteurellae, E. coli and Actinomycetae were isolated. The median value of the somatic cell count was 184,000 cells/ml. We consider coagulase-positive cocci therefore as the most pathogenic bacteria for the ovine udder.

Inappropriate detection of supraventricular arrhythmias by implantable dual chamber defibrillators: a comparison of four different algorithms.

Inappropriate therapy of supraventricular tachyarrhythmias by an ICD is still a common problem. Dual chamber (DDD) ICDs provide additional atrial sensing and should result in higher specificity for detection of supraventricular tachyarrhythmias. However, a direct comparison of different dual chamber algorithms has not been reported. The detection algorithms of four different DDD ICDs were tested: Phylax AV, Defender IV, Ventak AV III DR, and Gem DR 7271. Based on arrhythmias recorded from patients undergoing invasive electrophysiological studies and in many cases of catheter ablation at our institution, a library consisting of 71 supraventricular and 15 ventricular tachyarrhythmias was created. The library consists of episodes of atrial fibrillation, atrial flutter with different AV conduction, typical and atypical AV nodal reentrant tachycardia, AV reentrant tachycardia, sinus tachycardia, and ventricular tachycardia with and without ventriculoatrial conduction. Atrial fibrillation was appropriately classified by all four algorithms. However, the specificity for detection of other supraventricular tachyarrhythmias achieved by the Biotronik (12%) and the Guidant (11%) devices was significantly lower compared to the specificity of the ELA (28%) and the Medtronic DDD ICD (20%). This is due to the fact that the Biotronik and the Guidant algorithm classified all supraventricular tachyarrhythmias resulting in a stable ventricular rate as ventricular tachycardia, whereas the ELA and Medtronic algorithms performed a more detailed analysis by assessment of PR association, atrial onset, or timing of the atrial event relative to the ventricular event, respectively. Atrial fibrillation, the most common supraventricular tachyarrhythmia in patients with ICD, was detected by all devices.

Effect of fluid resuscitation with and without endothelin A receptor blockade on hemoconcentration and organ function in experimental pancreatitis.

BACKGROUND: Intravascular fluid loss contributes to pancreatitis-associated multiple organ dysfunction and is thus a major target for therapy in this life-threatening disease. AIM: To evaluate intravascular fluid loss and extravascular fluid sequestration together with cardiorespiratory and renal function in a well-established rat model of severe acute pancreatitis (AP) and to investigate the effect of fluid resuscitation with and without endothelin receptor A blockade on these parameters. METHOD: Induction of AP in rats by a standardized bile salt infusion into the pancreatic duct and intravenous cerulein hyperstimulation. Six hours after AP induction, animals were randomized into 4 groups to receive (1) no therapy; (2) 4 ml/kg/h Ringer's lactate (RL) i.v.; (3) 8 ml/kg/h RL i.v., or (4) 4 ml/kg/h RL plus an endothelin receptor antagonist. Target parameters measured before and after AP induction and during the 24-hour observation period included: mean arterial blood pressure, heart rate, hematocrit, arterial blood gases, urine production, ascites and pleural effusions. RESULTS: After 6 h, all animals presented with severe hemoconcentration (hematocrit >57%) and oliguria (<0.5 ml/6 h). Cardiorespiratory parameters were within the normal range. Up to 12 h after AP induction, animals without therapy had an increased hematocrit and oliguria and developed metabolic acidosis. Animals receiving fluid resuscitation had a significant drop in hematocrit and maintained compensated blood gas values. A significant increase in urine production was only observed in animals given 8 mg/kg/h RL. Between 12 and 24 h, urine production significantly increased with fluid resuscitation and respiratory parameters stabilized except for animals treated with 8 ml/kg/h RL which developed arterial hypoxia and hypercapnia. CONCLUSIONS: Intravascular fluid loss and extravascular fluid sequestration together with decreased urine production characterize the early phase of this model of severe AP. Massive fluid resuscitation necessary for increasing urine output may lead to respiratory distress. Reduction of intravascular fluid loss by endothelin receptor blockade is associated with improved renal and respiratory function.

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.

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.