Computational study of aortic hemodynamics for patients with an abnormal aortic valve: The importance of secondary flow at the ascending aorta inlet.

Blood flow in the aorta is helical, but most computational studies ignore the presence of secondary flow components at the ascending aorta (AAo) inlet. The aim of this study is to ascertain the importance of inlet boundary conditions (BCs) in computational analysis of flow patterns in the thoracic aorta based on patient-specific images, with a particular focus on patients with an abnormal aortic valve. Two cases were studied: one presenting a severe aortic valve stenosis and the other with a mechanical valve. For both aorta models, three inlet BCs were compared; these included the flat profile and 1D through-plane velocity and 3D phase-contrast magnetic resonance imaging derived velocity profiles, with the latter being used for benchmarking. Our results showed that peak and mean velocities at the proximal end of the ascending aorta were underestimated by up to 41% when the secondary flow components were neglected. The results for helical flow descriptors highlighted the strong influence of secondary velocities on the helical flow structure in the AAo. Differences in all wall shear stress (WSS)-derived indices were much more pronounced in the AAo and aortic arch (AA) than in the descending aorta (DAo). Overall, this study demonstrates that using 3D velocity profiles as inlet BC is essential for patient-specific analysis of hemodynamics and WSS in the AAo and AA in the presence of an abnormal aortic valve. However, predicted flow in the DAo is less sensitive to the secondary velocities imposed at the inlet; hence, the 1D through-plane profile could be a sufficient inlet BC for studies focusing on distal regions of the thoracic aorta.

Giant cell aortitis in treatment-naive human immunodeficiency virus and hepatitis C coinfection.

Giant cell arteritis is a common form of vasculitis, although involvement of the aorta is unusual. There is no established association between giant cell aortitis and human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection. We present the case of a 46-year-old female coinfected with HIV and HCV who had never received antiretroviral therapy and developed symptoms of deteriorating shortness of breath on exertion. Investigations demonstrated aortic root and ascending aorta dilatation, along with severe aortic valve regurgitation, for which the patient underwent valve-sparing aortic root replacement (a David procedure). Histopathology confirmed giant cell aortitis.

Minimally invasive direct coronary artery bypass versus off-pump coronary surgery through sternotomy.

INTRODUCTION: Although it is not a new technique, minimally invasive direct coronary artery bypass (MIDCAB) is employed only by a few surgeons in the UK. We compared our experience with MIDCAB with that of single vessel off-pump coronary artery bypass (OPCAB) graft surgery through a standard median sternotomy. METHODS: Patients who underwent either MIDCAB or OPCAB between April 2008 and July 2011 were reviewed. Exclusion criteria included patients with an ejection fraction of <0.5 or previous cardiac surgery. Data were obtained retrospectively from our prospective database, medical records and through general practitioners. RESULTS: Overall, 74 patients were analysed in the MIDCAB group and 78 in the OPCAB group. Their demographics and EuroSCORE (European System for Cardiac Operative Risk Evaluation) values were comparable (p>0.05). There was no statistically significant difference in the two groups in terms of mortality, recurrent myocardial infarction, postoperative stroke, wound infection, atrial fibrillation or need for reintervention. The MIDCAB group had six conversions to a sternotomy. Eight patients in each group required blood transfusion, with the average transfusion being 1.8 units in the MIDCAB group and 3.2 units in the OPCAB group. The mean duration of ventilation and intensive care unit stay was 5.0 hours and 38.4 hours in the MIDCAB group and 5.4 and 47.8 hours in the OPCAB group. The mean hospital stay was significantly reduced in the MIDCAB population (6.1 vs 8.5 days, p<0.05). CONCLUSIONS: MIDCAB can be performed safely in appropriately selected patients with outcomes comparable with OPCAB. The potential benefits include shorter hospital stay, reduced need for blood transfusion and faster recovery.

Surgical treatment of tricuspid valve endocarditis: a single-centre experience.

OBJECTIVES: We describe our ten-year experience with surgery for isolated tricuspid valve (TV) infective endocarditis. METHODS: Data were collected through a retrospective patient record review. Between 1999 and 2009, 13 (4.6%) patients had isolated TV surgery. The mean age was 40+/-15 years and there were nine male patients and 4 female patients. Eight (61%) patients were previous intravenous drug users. Indications for surgery included severe TV regurgitation (n=5), uncontrolled infection (n=4), septic pulmonary emboli (n=3) and TV stenosis (n=1). Staphylococcus aureus (n=3) and gram negative organisms (n=2) were isolated pre-operatively. Eleven patients had replacement surgery while two valves were repaired. RESULTS: There were no hospital deaths. Post-operative complications included new atrial fibrillation (n=5), re-operation (n=2), permanent pacemaker (n=2), and renal dialysis (n=1). Five (38%) patients died during the follow-up period. Cause of death was cardiac related in four patients. Actuarial survival was 63.1% at 3 years and 50.4% at 5 years. One patient developed recurrent TV endocarditis. There were no further cases of prosthetic valve failure. TV regurgitation remained trivial in both repaired valves. CONCLUSIONS: Surgery for isolated TV endocarditis is often associated with previous intravenous drug use. The procedure can be performed with acceptable hospital morbidity and no mortality. Late mortality is high, despite the young age of the patients.

Ureteral endometriosis: diagnosis and management.

Ureteral endometriosis is a rare disease with only about 300 cases reported. The diagnosis is difficult. The symptoms are non-specific and the diagnosis is based on abdominal ultrasonography suspicion confirmed by intravenous pyelography. The management of ureteral endometriosis usually requires surgery. Hormone therapy should be offered to patients of childbearing age who desire to have children and have the disease in an early stage. Open or laparoscopic surgical treatment gives long-term favorable results.

Cryosurgery for lung cancer: clinical results and technical aspects.

Lung carcinoma is the most frequently diagnosed malignancy in the world, with the incidence increasing through the 20th century. Presentation may be as a tumor mass primarily obstructing the central bronchial lumen, or a mass infiltrating lung tissue. Cryosurgery can be used as a method of palliative treatment for both these endobronchial and extrabronchial presentations. The aim of this study is two-fold: to present data relating to our extensive experience in treating obstructing endobronchial tumors and to present our initial results of direct cryosurgery to infiltrating lung tumor masses. During a nine-year period, 521 consecutive patients (male:female ratio 1.8:1) with a mean age of 67.9 years who had advanced obstructive tracheobronchial malignant tumors underwent cryosurgery with a mean of 2.4 treatments per patient. Hemoptysis, cough, dyspnoea and chest pain improved by at least one class in 76.4%, 69.0%, 59.25% and 42.6% (p<0.01) of symptomatic patients respectively. Quality of life studies showed that the mean Karnofsky score improved from 60 +/- 7 to 75 +/- 8 and the mean WHO score from 3.04 +/- 0.7 to 2.20 +/- 0.56. There were 7 (1.2%) in-hospital deaths, and 2-year survival was 15.9%. Direct cryosurgery to carcinoma of the lung was performed on 15 patients at exploratory thoracotomy. Results showed an increase in FEV1 from 1.80 +/- 0.6 liters to 1.95 +/- 0.8 (8.3%) liters and in FVC from 2.50 +/- 0.8 to 2.68 +/- 0.8 liters (7.2%). The Karnofsky score improved from 68 +/- 9 to 78 +/- 10 and the WHO score from 2.63 +/- 0.81 to 2.38 +/- 0.78 (9.6%). Major symptoms including cough, dyspnoea, and hemoptysis were assessed and showed improvement in 77.8%, 66.7%, and 100% (p<0.01) of symptomatic patients respectively. Patients were followed for a mean period of 18 months (range 4-84 months). Median survival from the date of surgery (Kaplan-Meier, 95%Cl) was 11.6 (6.8 to 18.2) months, range 1 to 84 months. Cryosurgery provides a safe and effective method for the palliation of advanced central bronchial obstructive tumors, and compares favorably with other methods in terms of safety, cost, and complications. Initial experience suggests that similar palliation may be achieved by cryosurgery applied to advanced parenchymal tumor masses.

[Pregnancy and inflammatory bowel disease]. / Sarcina si bolile inflamatorii intestinale idiopatice.

Inflammatory bowel disease (IBD)--Crohn's disease, ulcerative colitis--affects frequently the women in their childbearing years with concerns about both on pregnancy and evolution of the IBD. Important issues concerning a pregnant woman with IBD include the effect of pregnancy on the disease, and, conversely, the effect of IBD on pregnancy and inheritance of IBD in the offspring. Adverse fetal outcomes are not increased when IBD is inactive; however, women with active disease incur a greater risk of premature birth. Most of women with active IBD at the time of contraception have continued or worsening disease activity during pregnancy. Most medications for IBD are safe during pregnancy, with notable exceptions. A key principle of management is that active disease, not therapy, poses the greatest risk to pregnancy.

An evaluation of existing risk stratification models as a tool for comparison of surgical performances for coronary artery bypass grafting between institutions.

OBJECTIVE: Risk stratification systems are used in cardiac surgery to estimate mortality risk for individual patients and to compare surgical performance between institutions or surgeons. This study investigates the suitability of six existing risk stratification systems for these purposes. METHODS: Data on 5471 patients who underwent isolated coronary artery bypass grafting at two UK cardiac centres between 1993 and 1999 were extracted from a prospective computerised clinical data base. Of these patients, 184 (3.3%) died in hospital. In-hospital mortality risk scores were calculated for each patient using the Parsonnet score, the EuroSCORE, the ACC/AHA score and three UK Bayes models (old, new complex and new simple). The accuracy for predicting mortality at an institutional level was assessed by comparing total observed and predicted mortality. The accuracy of the risk scores for predicting mortality for a patient was assessed by the Hosmer-Lemeshow test. The receiver operating characteristic (ROC) curve was used to evaluate how well a system ranks the patient with respect to their risk of mortality and can be useful for patient management. RESULTS: Both EuroSCORE and the simple Bayes model were reasonably accurate at predicting overall mortality. However predictive accuracy at the patient level was poor for all systems, although EuroSCORE was accurate for low to medium risk patients. Discrimination was fair with the following ROC areas: Parsonnet 0.73, EuroSCORE 0.76, ACC/AHA system 0.76, old Bayes 0.77, complex Bayes 0.76, simple Bayes 0.76. CONCLUSIONS: This study suggests that two of the scores may be useful in comparing institutions. None of the risk scores provide accurate risk estimates for individual patients in the two hospitals studied although EuroSCORE may have some utility for certain patients. All six systems perform moderately at ranking the patients and so may be useful for patient management. More results are needed from other institutions to confirm that the EuroSCORE and the simple Bayes model are suitable for institutional risk-adjusted comparisons.

Validation of four different risk stratification systems in patients undergoing off-pump coronary artery bypass surgery: a UK multicentre analysis of 2223 patients.

BACKGROUND: Various risk stratification systems have been developed in coronary artery bypass graft surgery (CABG), based mainly on patients undergoing procedures with cardiopulmonary bypass. OBJECTIVE: To assess the validity and applicability of the Parsonnet score, the EuroSCORE, the American College of Cardiology/American Heart Association (ACC/AHA) system, and the UK CABG Bayes model in patients undergoing off-pump coronary artery bypass surgery (OPCAB) in the UK. METHODS: Data on 2223 patients who underwent OPCAB in eight cardiac surgical centres were collected. Predicted mortality risk scores were calculated using the four systems and compared with observed mortality. Calibration was assessed by the Hosmer-Lemeshow (HL) test. Discrimination was assessed using the receiver operating characteristic (ROC) curve area. RESULTS: 30 of 2223 patients (1.3%) died in hospital. For the Parsonnet score the HL test was significant (p < 0.001) and the receiver operating characteristic curve (ROC) area was 0.74. For the EuroSCORE the HL test was also significant (p = 0.008) and the ROC area was 0.75. For the ACC/AHA system the HL test was non-significant (p = 0.7) and the ROC area was 0.75. For the UK CABG Bayes model the HL test was also non-significant (p = 0.3) and the ROC area was 0.81. CONCLUSIONS: The UK CABG Bayes model is reasonably well calibrated and provides good discrimination when applied to OPCAB patients in the UK. Among the other three systems, the ACC/AHA system is well calibrated but its discrimination power was less than for the UK CABG Bayes model. These data suggest that the UK CABG Bayes model could be an appropriate risk stratification system to use for patients undergoing OPCAB in the UK.

Gastropleural fistula originating from the lesser curve: a recognised complication, an uncommon pathway of communication.

Fistulous communications between the abdominal and the pleural cavity are rare; they implicate intra-abdominal sepsis. We present a rare case of subphrenic abscess following gastric perforation, which resulted in thoracic empyema. This report emphasises that gastropleural fistulas, although uncommon, should be considered in differential diagnoses of thoracic empyema, especially when there is a longstanding history of peptic ulceration.

Systemic inflammation and cardiac surgery: an update.

Cardiac surgery with cardiopulmonary bypass (CPB) is associated with the development of a systemic inflammatory response that can often lead to dysfunction of major organs. The systemic inflammation can be assessed intra- and postoperatively by measuring concentrations of inflammatory mediators in plasma and tissues. These concentrations, however, do not always correlate with the degree of observed organ dysfunction. Various strategies have been used to reduce inflammatory phenomena in patients undergoing CPB. Cardiac surgery without CPB has been performed increasingly with satisfactory results over the past few years. Attenuation of systemic inflammation and improved outcome in high risk patients are potential benefits of this technique. The emergence and expanding performance of cardiac surgical procedures without the use of CPB has given us an excellent tool to investigate the relative importance of CPB as a cause of systemic inflammation. Aprotinin is a protease inhibitor which is used in cardiac surgical patients for its haemostatic effects. Aprotinin has anti-inflammatory properties, the nature of which have not been completely clarified. This article presents a summary of the published literature investigating inflammatory response and organ dysfunction in patients who have cardiac surgery without CPB. It also presents an overview of recent data on the anti-inflammatory action mechanisms of aprotinin.

The effect of circuit surface area on CD11b(mac-1) expression in a rat recirculation model.

The aim of the study was to assess the effect of exposed surface area of diethylhexylphthalate plasticized polyvinylchloride (PVC) on the expression of the adhesion molecule CD11b(mac-1) on neutrophils and to determine whether there is any apparent advantage in the current trend in reducing circuit surface area in terms of neutrophil activation. The study was carried out using a parallel plate rodent recirculation biomaterial testing model on 4 groups of 10 adult male Sprague Dawley rats weighing between 350 and 450 g. One group comprised the control group in which there was no biomaterial exposure. In the remaining 3 groups, the animals were subjected to either high (48 cm2), intermediate (24 cm2), or low (12 cm2) biomaterial surface area exposure. The parallel plate test cell was connected to the right femoral circulation and recirculation initiated at a flow rate of 1.5 ml/min for a period of 60 min. Blood samples were taken at 0, 30, and 60 min for the assessment of CD11b expression. Cd11b was assessed using flow cytometric analysis on neutrophils. The results demonstrated that there was a surface area related effect in the upregulation of CD11b. The difference at the terminal sample point between the highest surface area group (293.95 +/- 18.57%) and the low surface area group (133.80 +/- 49.31%) was highly statistically significant (p < 0.001). These results demonstrate that there may be some gain in terms of reduced inflammatory response from reducing the exposed surface area of PVC in extracorporeal perfusion circuits.

Effect of aprotinin on endothelial cell activation.

BACKGROUND: Cardiopulmonary bypass surgery is often accompanied by a systemic inflammatory response, which can lead to postoperative complications in high-risk patients. This is mediated in part through a systemic rise in inflammatory cytokine levels and the sequestration of leukocytes within organs. Aprotinin has previously been shown to exert an anti-inflammatory effect by preventing the capacity of leukocytes to transmigrate through vascular endothelium. Here we have focused on whether aprotinin has an effect on endothelial cell activation and adhesion molecule expression in response to tumor necrosis factor-alpha, particularly with reference to whether aprotinin inhibits tumor necrosis factor-stimulated neutrophil transendothelial migration. METHODS AND RESULTS: Intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin expression was studied in tumor necrosis factor-alpha-activated human umbilical vein endothelial cells in the presence of aprotinin at 200, 800, and 1600 kIU/mL. Aprotinin inhibited tumor necrosis factor-alpha-stimulated expression of intercellular adhesion molecule-1 (P =.019 at 1600 kIU/mL) and vascular cell adhesion molecule-1 (P =.003 at 1600 kIU/mL) but not E-selectin. Similar results were obtained in the dermal microvascular endothelial cell line, HMEC-1, which exhibited diminished intercellular adhesion molecule-1 expression in the presence of aprotinin (P =.040 at 800 kIU/mL and P <.001 at 1600 kIU/mL). Aprotinin also significantly inhibited neutrophil transmigration across tumor necrosis factor-alpha-activated human umbilical vein endothelial cells (P =.046 at 1600 kIU/mL). CONCLUSIONS: We have demonstrated that aprotinin inhibits intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, but not E-selectin, expression on tumor necrosis factor-alpha-activated endothelial cells and that transendothelial migration by neutrophils is also specifically suppressed under these conditions. Our results indicate that endothelial cells can be specifically targeted by aprotinin, therefore adding to our understanding of the anti-inflammatory mechanism of action of aprotinin during cardiopulmonary bypass.

Vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 serum level in patients with chest pain and normal coronary arteries (syndrome X).

BACKGROUND: Plasma levels of soluble vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) mediators of leukocyte adhesion to vascular endothelium may implicate in the pathogenesis of the syndrome of chest pain with normal coronary arteries. HYPOTHESIS: We attempted to determine whether markers of endothelial activation are raised in patients with chest pain and normal coronary arteries. METHODS: We measured plasma VCAM-1, ICAM-1 (ng/ ml) in 36 patients (34 men, 2 women, aged 62 +/- 9 years) with stable angina, coronary artery disease (CAD), and a positive response to exercise test; in 21 patients (6 men, 15 women, aged 56 +/- 9 years) with chest pain and normal coronary arteriograms (syndrome X); and in 11 healthy control subjects (8 men, 3 women, aged 49 +/- 14 years). RESULTS: Plasma ICAM-1 levels were significantly higher both in patients with CAD (mean +/- standard error of the mean) (328 +/- 26, p < 0.05), and in syndrome X (362 +/- 22, p < 0.01) than in controls (225 +/- 29). VCAM-1 levels were also higher in syndrome X (656 +/- 42 ng/ml) and in patients with CAD (626 +/- 42 ng/ml) than in controls (551 +/- 60, p = 0.09). CONCLUSIONS: ICAM-1 and VCAM-1 levels are increased both in patients with CAD and with syndrome X compared with control individuals. These findings may suggest the presence of chronic inflammation with involvement of the endothelium in patients with anginal chest pain and normal coronary angiograms.

Effect of aprotinin (trasylol) on the inflammatory and thrombotic complications of conventional cardiopulmonary bypass surgery.

Before the discovery of its hemostatic properties, aprotinin was thought of as a potential anti-inflammatory agent. Its clinical introduction in 1987 to prevent blood loss during cardiac surgery [Royston 1987, van Oeveren 1987] led to its anti-inflammatory benefits being largely overlooked in favor of a vigorous debate centering on whether aprotinin may be pro-thrombotic when given to patients. In this article, we summarize evidence for the anti-inflammatory activity of aprotinin and discuss our recent contributions in this area. We also summarize the state of the thrombosis debate and discuss our recent evidence from purified platelets which shows that aprotinin is simultaneously hemostatic yet anti-thrombotic.

Increased plasma adhesion molecule levels in patients with heart failure who have ischemic heart disease and dilated cardiomyopathy.

BACKGROUND: Inflammatory mechanisms, including leukocyte activation, appear to play a pathogenetic role in the development of heart failure. Vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) are important mediators of leukocyte adhesion to vascular endothelium. The plasma levels of the soluble form of these molecules may be elevated in chronic inflammation. METHODS AND RESULTS: We measured plasma VCAM-1 and ICAM-1 levels (in nanograms per milliliter) with the commercially available enzyme-linked immunosorbent assay method in 12 patients (9 male, 3 female, aged 64 +/- 8 years) with dilated cardiomyopathy and heart failure, in 23 patients (23 male, aged 65 +/- 9 years) with ischemic cardiomyopathy and heart failure, and in 11 healthy control subjects (8 male, 3 female, aged 49 +/- 14 years). Plasma ICAM-1 levels were higher both in patients with dilated cardiomyopathy (363 +/- 77 ng/mL, P <.05) (mean +/- SEM) and in those with ischemic heart disease (320 +/- 32 ng/mL, P <.05) than in control subjects (225 +/- 29 ng/mL). VCAM-1 levels were also higher in both groups with heart failure (664 +/- 73 ng/mL) than in control subjects (551 +/- 60 ng/mL). VCAM-1 levels were higher in patients with class IV compared with those with class II and III heart failure. CONCLUSIONS: Plasma adhesion molecule levels are increased in patients with heart failure and are unrelated to the presence or absence of angiographically demonstrable atherosclerotic coronary artery disease. The plasma level of VCAM-1 correlates with the severity of heart failure.

Leucodepletion during cardiopulmonary bypass reduces blood transfusion and crystalloid requirements.

Cardiopulmonary bypass (CPB) is associated with the production of inflammatory responses, which can have significant influence on prognosis. We studied the effects of leucocyte-depletion filters on inflammatory parameters and early postoperative prognosis during coronary revascularization. Twenty patients undergoing elective coronary revascularization were randomly divided into two groups. Ten patients had leucocyte-depletion filters added to the CPB circuit (treatment group) and 10 were used as control cases (control group). Expression of CD11b on neutrophils, and production of myeloperoxidase and lactoferrin, were measured in arterial samples between induction and 3 h postbypass. In addition, clinical parameters were measured during inpatient recovery. CD11b neutrophil expression, and myeloperoxidase and lactoferrin production, were found to be upregulated during CPB and then to decline to preoperative levels by the third postoperative hour. Blood transfusion requirements were reduced in the treatment group, equalling 1.5 +/- 1.2 units, compared to 2.7 +/- 1.1 units for the control group (p value = 0.034) and so were the volumes of crystalloid infused during the first 24 h postoperatively, equalling 3.9 +/- 1.21 in the treatment group and 3.3 +/- 0.71 in the control group (p value = 0.021). Overall, the application of leucocyte depletion produced an early clinical advantage, underlining the need for an improved understanding and manipulation of the inflammatory response to CPB.

The antithrombotic and antiinflammatory mechanisms of action of aprotinin.

Aprotinin (Trasylol) is generally regarded to be an effective hemostatic agent that prevents blood loss and preserves platelet function during cardiac surgery procedures requiring cardiopulmonary bypass (CBP). However, its clinical use has been limited by the concern that such a potent hemostatic agent might be prothrombotic, particularly in relation to coronary vein graft occlusion. In this review we present a mechanism of action that challenges such a viewpoint and explains how aprotinin can be simultaneously hemostatic and antithrombotic. Aprotinin achieves these two apparently disparate properties by selectively blocking the proteolytically activated thrombin receptor on platelets, the protease-activated receptor 1 (PAR1), while leaving other mechanisms of platelet aggregation unaffected. We also review recent research leading to the discovery of novel antiinflammatory targets for aprotinin. A better understanding of its mechanisms of action has led to the conclusion that aprotinin is a remarkable drug with the capacity to correct many of the imbalances that develop in the coagulation system and the inflammatory system after CPB. Nonetheless, it has been clinically underused for fear of causing thrombotic complications, a fear that in light of recent evidence may be unfounded.

Inhibition of neutrophil L-selectin shedding: a potential anti-inflammatory effect of aprotinin.

The cardiopulmonary bypass (CPB)-related inflammatory response involves leucocyte activation and increased leucocyte-endothelial cell interaction. L-selectin is an adhesion molecule expressed on the surface of leucocytes which participates in the initial rolling step of the leucocyte-endothelial cell adhesion cascade. L-selectin is proteolytically cleaved off the surface of leucocytes when they become activated, an event that is regarded as a marker of leucocyte activation. Aprotinin is a protease inhibitor that has been used in cardiac surgery as a haemostatic agent and also exhibits certain anti-inflammatory properties. In this study, peripheral venous blood from volunteers was pre-incubated with aprotinin at 200, 800 and 1600 kallikrein inhibiting units (kiu)/ml and stimulated with the chemoattractants N-formyl-methyl-leucyl-phenylalanine (fMLP) or platelet activating factor (PAF). Surface expression of L-selectin on neutrophils was measured using a monoclonal antibody and flow cytometry. The results demonstrate that aprotinin inhibits shedding of L-selectin in a dose-dependent fashion (p=0.0278 and 0.0005, respectively, at 800 and 1600 kiu/ml for fMLP-stimulated shedding; p=0.0017 and 0.0010, respectively, at 200 and 800 kiu/ml for PAF-stimulated shedding). This effect may be of significance with respect to the anti-inflammatory action of aprotinin in patients undergoing CPB.

An anti-inflammatory property of aprotinin detected at the level of leukocyte extravasation.

BACKGROUND: Aprotinin is a serine protease inhibitor used extensively in cardiac operations to reduce postoperative bleeding. It has also been used in trials aimed at reducing the systemic inflammatory response to cardiopulmonary bypass. It remains unclear whether the anti-inflammatory action of aprotinin is related to its general ability to suppress leukocyte activation or whether aprotinin can exercise effects during the leukocyte-endothelial cell adhesion cascade. METHODS: We used intravital microscopy to study the 3 main stages of the adhesion cascade (leukocyte rolling, firm adhesion, and extravasation) within the mesenteric microcirculation of rats. This in vivo technique allows leukocyte recruitment to be viewed directly through the transparent mesentery of anesthetized animals. RESULTS: Aprotinin, given by continuous infusion at a clinically relevant dose, exerted no effect on the rolling or firm adhesion responses toward local chemoattractant N -formyl-methyl-leucyl-phenylalanine but significantly inhibited extravasation of leukocytes (73% at 40 minutes, P =.04) into surrounding tissues. In parallel in vitro experiments, aprotinin (used at 200, 800, and 1600 kIU/mL) dose dependently inhibited neutrophil transmigration through cultured endothelial cells in response to 3 different chemoattractants: N -formyl-methyl-leucyl-phenylalanine (P <.001 at 800 and 1600 kIU/mL), interleukin 8 (P <.05 at 200 kIU/mL and P <.001 at 800 and 1600 kIU/mL), and platelet-activating factor (P <.05 at 1600 kIU/mL). CONCLUSIONS: Our studies have therefore revealed a novel anti-inflammatory mechanism of aprotinin operating at the level of leukocyte extravasation. These findings may be relevant in the prevention of systemic inflammation after cardiopulmonary bypass through the use of protease inhibitors.