Thomas Vukovich

Inflammatory response and myocardial injury following coronary artery bypass grafting with or without cardiopulmonary bypass.

OBJECTIVE In coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) the inflammatory response is suggested to be minimized. Coronary anastomoses are performed during temporary coronary occlusion. Inflammatory response and myocardial ischaemia need to be studied in a randomized study comparing CABG in multivessel disease with versus without CPB. METHODS Following randomization 30 consecutive patients received CABG either with (n=16) or without CPB (n=14). Primary study endpoints were parameters of the inflammatory response (interleukin (IL)-6, interleukin-10, ICAM-1, P-selectin) and of myocardial injury (myoglobin, creatine kinase-MB (CK-MB), troponin I) (intraoperatively, 4, 8, 16, 24 and 48 h after surgery). The secondary endpoint was clinical outcome. RESULTS The incidence of major (death: CABG with CPB n=1, not significant (n.s.)) and minor adverse events (wound infection: with CPB n=2, without CPB n=1, n.s. ; atrial fibrillation: with CPB n=3, without CPB n=2, n.s.) was comparable between both groups. The release of IL-6 was comparable during 8 h of observation (n.s.). Immediately postoperatively IL-10 levels were higher in the operated group with CPB (211.7+/-181.9 ng/ml) than in operated patients without CPB (104.6+/-40.3 ng/ml, P=0.0017). Thereafter no differences were found between both groups. A similar pattern of release was observed in serial measures of ICAM-1 and P-selectin, with no difference between both study groups (n.s.). Eight hours postoperatively the cumulative release of myoglobin was lower in operated patients without CPB (1829.7+/-1374. 5 microg/l) than in operated patients with CPB (4469.8+/-4525.7 microg/l, P=0.0152). Troponin I release was 300.7+/-470.5 microg/l (48 h postoperatively) in patients without CPB and 552.9+/-527.8 microg/l (P=0.0213). CK-MB mass release was 323.5+/-221.2 microg/l (24 h postoperatively) in operated patients without CPB and 1030. 4+/-1410.3 microg/l in operated patients with CPB (P=0.0003). CONCLUSIONS This prospective randomized study suggests that in low-risk patients the impact of surgical access on inflammatory response may mimic the influence of long cross-clamp and perfusion times on inflammatory response. Our findings indicate that multiregional warm ischaemia, caused by snaring of the diseased coronary artery, causes considerably less myocardial injury than global cold ischaemia induced by cardioplegic cardiac arrest.

Replacement therapy for a homozygous protein C deficiency-state using a concentrate of human protein C and S

A severe congenital deficiency of protein C was diagnosed in a 10‐month‐old girl who had been suffering from skin necrosis since the age of 7 months. The patient was treated initially with fresh frozen plasma, 10 ml per kg body weight, every 24 h. Following treatment, the mean plasma level of protein C was 0.1 U/ml after 30 min and less than 0.02 U/ml after 24 h. The child was then treated with a concentrate of human protein C and S, 100 U protein C per kg body weight, given every 48 h for a period of 9 months. The mean plasma level of protein C was 0.93 U/ml 30 min after administration of the concentrate and 0.13 and 0.08 U/ml after 24 and 48 h, respectively. The mean post‐transfusional in vivo recovery of protein C was 44% and the half life was 8.3 h. The mean plasma level of ‘free’protein S increased from 1.1 to 2.2 U/ml after administration of the concentrate. There was no increase in ‘bound’protein S. The in vivo recovery of ‘free’protein S was 49% and the half life was about 17 h. Since the start of this replacement therapy using a human protein C and S concentrate, the patient has not developed any thromboembolic complications. These results indicate the therapeutic value of human protein C and S concentrate in the treatment of severe protein C deficiency.

Management of serious staphylococcal infections in the outpatient setting

SummaryPatients with serious staphylococcal infections, e.g. endocarditis and osteomyelitis, need prompt and prolonged parenteral antibiotic treatment to ensure eradication of the causative pathogen. The major cost in the treatment of these infections is the long period of hospitalisation required for the administration of intravenous antibiotics. To shorten the hospitalisation period, outpatient treatment can be given to some patients.In this study, patients with acute exacerbations of chronic osteomyelitis (n=44) or endocarditis (n=10) were treated with intravenous teicoplanin. The pathogens were Staphylococcus aureus (n=41,13 of which were methicillin resistant) and coagulase-negative staphylococci (n=13, one of which was methicillin resistant). After a mean loading dose of 15 mg/kg for 3 to 10 days, patients received teicoplanin 3 times a week at a dose (mean 15 mg/kg) individualised to achieve serum trough concentrations of approximately 10 mg/L for osteomyelitis and 20 mg/L for endocarditis. Treatment duration ranged from 28 to 150 (mean 62) days for patients with osteomyelitis and from 28 to 88 (mean 49) days for patients with endocarditis. 37 (84%) patients with osteomyelitis and 8 (80%) patients with endocarditis were treated successfully. Adverse events were ob-served in 9 patients and included rash (n=3), thrombocytopenia (n=3), and drug fever, pseudomembranous colitis, nausea, leucopenia and transient hearing impairment (one patient each).In conclusion, this study demonstrates that teicoplanin can be administered successfully in an outpatient setting according to a 3-times weekly schedule for the treatment of patients with staphylococcal osteomyelitis and endocarditis.

Basal high-sensitivity-C-reactive protein levels in patients with spontaneous venous thromboembolism

The role of C-reactive protein (CRP) in venous thromboembolism (VTE) is still under discussion because of controversial results in the literature. Conflicting data may have partly been due to bias by exogenous factors altering CRP levels. We investigated CRP concentrations in patients with spontaneous VTE applying a study design that allowed the measurement of basal high sensitivity (hs)-CRP levels. Patients with a history of deep vein thrombosis (DVT, n=117) and pulmonary embolism (PE, n=97) were compared to healthy individuals (n=104). Hs-CRP levels (mg/dl) were significantly higher in patients (n=214, median/interquartile range: 0.171/0.082-0.366) than in controls (0.099/0.053-0.245, p=0.001). The unadjusted odds ratio (OR) for VTE per 1 mg/dl increase of CRP was 2.8 [95% confidence interval (CI): 1.1-6.8, p=0.03]. This association remained significant after adjustment for factor V Leiden, prothrombin G20210A and factor VIII activity above 230% (OR = 2.9, 95% CI [1.1-7.5]), but became remarkably attenuated and lost its statistical significance after adjustment for BMI alone (OR = 1.7 [0.7-4.0]). CRP was also not independently associated with VTE in subgroups of patients (those with DVT without symptomatic PE, those with PE and patients without established risk factor) in multiple regression analysis. In summary, we observed significantly higher basal hs-CRP levels in patients with spontaneous VTE compared to healthy controls. This association was independent of hereditary and laboratory risk factors for VTE, but lost its significance after adjustment for BMI. Increased basal CRP levels do not appear to represent an independent risk factor for VTE.

Is Low Serum Bilirubin an Independent Risk Factor for Coronary Artery Disease in Men but Not in Women

For many years, the bile pigment bilirubin was considered to be only a toxic waste product formed during heme catabolism. Recent evidence, however, suggests that bilirubin acts as a potent physiologic antioxidant that may provide important protection against arteriosclerosis, coronary artery disease (CAD), and inflammation (1)(2)(3). The antioxidant capacity of bilirubin and its potent ability to scavenge peroxyl radicals have led to the concept that mildly increased circulatory bilirubin may have a physiologic function to protect against disease processes that involve oxygen and peroxyl radicals (4). Indeed, inverse correlations between the presence of CAD and total bilirubin concentrations in the circulation were reported recently in several independent studies (5)(6). Additionally, plasma bilirubin correlates inversely with several established risk factors for CAD, including smoking, increased LDL-cholesterol, diabetes, and obesity, but is directly proportional to the protective factor HDL-cholesterol (5)(7). The effect of bilirubin on the risk of cardiovascular disease is apparent in men (8) but is less clear in women (6)(9)(10). In the present study, we therefore examined the influence of gender on total bilirubin concentrations. All patients referred to the Department of Cardiology, University of Vienna, between August 1999 and September 2001 for whom clinical data were available were included in our study. Patients were divided in a CAD and a non-CAD group. The CAD group consisted of 544 patients (157 females and 387 males) with clinically relevant CAD. Clinically relevant CAD was defined as an exercise-induced ischemic ST-segment depression >0.1 mV (12%) (11) and/or a history of myocardial infarction (53%) or coronary intervention [coronary artery bypass (8%) or percutaneous transluminal coronary angioplasty (27%)]. In the non-CAD group (359 patients; 186 females and 173 males), the presence of CAD …

The angiotensin-converting enzyme insertion/deletion polymorphism and serum levels of angiotensin-converting enzyme in venous thromboembolism : Data from a case control study

The angiotensin-converting enzyme (ACE) has been suggested to affect blood coagulation and fibrinolysis. Results from literature on the role of the frequent insertion/deletion (I/D) polymorphism in the ACE gene in venous thromboembolism (VTE) are controversial. Only limited data on ACE serum levels inVTE exist. We determined the ACE I/D polymorphism by genotyping and ACE serum levels by an enzymatic assay in 100 high-risk patients with objectively confirmed recurrentVTE and at least one event of an unprovoked deep venous thrombosis or pulmonary embolism. One hundred twenty-five age- and sex-matched healthy individuals served as controls. ACE genotype frequencies were not significantly different between patients (DD: 26.0%, ID: 52.0%, II: 22.0%) and controls (DD: 29.6%, ID: 44.8%, II: 25.6%; p = 0.56). Neither individuals with ACE DD genotype nor those with ACE ID genotype had a higher risk for VTE in comparison to those with ACE II genotype (odds ratio and [95% confidence interval]: 1.0 [0.5-2.1] and 1.4 [0.7-2.6], respectively). Serum ACE levels (U/l) did not differ between patients (median = 25.25, 25th -75th percentile: 20.20-33.70) and controls (24.20, 17.85-34.50, p = 0.49). In the total population involved in the study the ACE DD genotype (n = 63: 36.00 [26.40-43.00]) was associated with higher ACE levels than the ACE ID genotype (n = 108: 24.10 [19.80-31.48], p < 0.001) and the ACE II genotype (n = 54: 19.35 [15.00-22.95], p < 0.001). In conclusion, we found a significant association of the ACE I/D polymorphism with ACE serum levels. However, neither the serum levels nor the I/D genotype were associated with VTE.

The effect of near-normoglycaemic control on plasma levels of coagulation factor VII and the anticoagulant proteins C and S in insulin-dependent diabetic patients.

The present prospective follow‐up study was made to study the effect of glycaemic regulation on levels of factor VII, protein C and protein S in 15 insulin‐dependent diabetic patients without manifestations of vascular disease. Patients were tested before and after 8 weeks of ‘metabolic’ intervention, whereby a near‐normoglycaemic state was achieved. At baseline, values of cross‐linked fibrin degradation products (XL‐FDP) and levels of ‘total’ protein S were significantly increased and protein C values were decreased in the diabetic patients when compared to control subjects, whereas levels of factor VII and ‘free’ protein S were near normal. After ‘metabolic’ intervention a decrease of all haemostatic parameters were recorded, however XL‐FDP levels did not decline to control levels and the imbalance of factor VII and protein C persisted. When patients with newly diagnosed diabetes (n= 8) were compared to those with long‐term disease (n= 7) higher levels of factor VII, protein C and protein S were recorded in the latter group before and after metabolic intervention; at baseline the differences reached statistical significance for factor VII and protein S, and remained significant for factor VII after metabolic intervention. Before and after intervention XL‐FDP levels were higher in patients with newly diagnosed disease than in patients with long‐term diabetes. The correlation analysis revealed positive correlations of factor VII, protein C and protein S to cholesterol and triglycerides, of protein S to all glycaemic control parameters, negative correlations of protein C to glucose, and of XL‐FDP to factor VII, protein C and protein S. The results indicate an imbalance of haemostasis towards thrombophilicity in insulin‐dependent diabetic patients, not completely correctable by glycaemic control.

Evaluation of a Turbidimetric Denka Seiken C-Reactive Protein Assay for Cardiovascular Risk Estimation and Conventional Inflammation Diagnosis

Measurement of C-reactive protein (CRP) is used for conventional inflammation diagnosis (1) and diagnosis of low-grade inflammation for risk estimation of cardiovascular events (2)(3). Because diagnostic measurement ranges for those two indications differ by two orders of magnitude, different methods or different applications of one method must be used at present to cover both diagnostic measurement ranges (4)(5). The aim of this study was to evaluate the analytical performance of the Denka Seiken turbidimetric CRP assay compared with the Dade Behring nephelometric assay across a concentration range of 0.2–300 mg/L. For this evaluation, leftover material was used, which is in concordance with the European Law for Medical and Diagnostic Products. For precision and linearity studies, we prepared serum pools from blood samples with previously measured CRP (BN II nephelometer; Dade Behring). The low and high pools were prepared by combining samples with CRP <1 and 200–300 mg/L, respectively. The high pool was diluted with the low pool to the following final percentages of high pool: 100%, 33%, 11%, 3.7%, 1.2%, 0.41%, 0.14%, and 0%. The dilutions were aliquoted and stored at −20 …

Diagnostic Value of Hemostatic Parameters for Prediction of Complications in Patients Undergoing Aorto-Coronary Bypass Grafting

Though there has been rapid progress in coronary bypass surgery, postoperative hemostatic disorders due to extracorporeal circulation (ECC) are one of the remaining obstacles of this technique. Thrombocytopenia and platelet dysfunction [5], hyperfibrinolysis [3, 7] or activation of the anticoagulant system [4] going along with consumption of pro- and anticoagulant proteins [3–5] can cause extensive postoperative bleeding. Furthermore, the activation of intravasal coagulation might be the pathophysiological base for complex postoperative complications [4]. Thus, the aim of this study was to investigate whether a reduction in the preoperative thromboresistant potential quantified by various hemostatic parameters is linked to intra- or postoperative complications.