Gerda Falkensammer

Blood coagulation activation and fibrinolysis during a downhill marathon run.

Prolonged physical exercise is associated with multiple changes in blood hemostasis. Eccentric muscle activation induces microtrauma of skeletal muscles, inducing an inflammatory response. Since there is a link between inflammation and coagulation we speculated that downhill running strongly activates the coagulation system. Thirteen volunteers participated in the Tyrolean Speed Marathon (42 195 m downhill race, 795 m vertical distance). Venous blood was collected 3 days (T1) and 3 h (T2) before the run, within 30 min after finishing (T3) and 1 day thereafter (T4). We measured the following key parameters: creatine kinase, myoglobin, thrombin–antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin–α2-antiplasmin complexes, tissue-type plasminogen activator antigen, plasminogen-activator-inhibitor-1 antigen and thrombelastography with ROTEM [intrinsic pathway (InTEM) clotting time, clot formation time, maximum clot firmness, alpha angle]. Thrombin generation was evaluated by the Thrombin Dynamic Test and the Technothrombin TGA test. Creatine kinase and myoglobin were elevated at T3 and further increased at T4. Thrombin–antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin–α2-antiplasmin complexes, tissue-type plasminogen activator antigen and plasminogen-activator-inhibitor-1 antigen were significantly increased at T3. ROTEM analysis exhibited a shortening of InTEM clotting time and clot formation time after the marathon, and an increase in InTEM maximum clot firmness and alpha angle. Changes in TGA were indicative for thrombin generation after the marathon. We demonstrated that a downhill marathon induces an activation of coagulation, as measured by specific parameters for coagulation, ROTEM and thrombin generation assays. These changes were paralleled by an activation of fibrinolysis indicating a preserved hemostatic balance.

Chronic antiepileptic monotherapy, bone metabolism, and body composition in non-institutionalized children.

Aim  The aim of this study was to determine the influence of chronic monotherapy with antiepileptic drugs (AEDs) on vitamin D levels, bone metabolism, and body composition.

Limited utilities of N-terminal pro B-type natriuretic peptide and other newer risk markers compared with traditional risk factors for prediction of significant angiographic lesions in stable coronary artery disease

Objective: To investigate the usefulness of N-terminal pro-brain natriuretic peptide (NT-proBNP) as a predictive marker for angiographically significant coronary artery disease (CAD) and CAD severity compared with other newer biochemical risk markers and classic risk factors in patients with clinically suspected CAD. Design: Cross-sectional evaluation of NT-proBNP in a large consecutive series of patients without a history of myocardial infarction referred for elective coronary angiography (CAG) between March 2004 and January 2005. The value of NT-proBNP for predicting CAD was assessed and compared with high sensitivity C-reactive protein (hs-CRP), γ-glutamyltransferase (GGT) and traditional risk factors. Setting: Tertiary care centre, Department of Cardiology, Innsbruck Medical University, Austria. Patients: 561 men and 287 women aged between 20–86 years (median 65 years). Interventions: None. Main outcome measures: Association of NT-proBNP with the severity of CAD, left ventricular dysfunction and comparison of predictive values of NT-proBNP, hs-CRP, GGT and traditional CAD risk factors. Results: Of all tested newer biochemical risk markers NT-proBNP performed best. In a multinomial logistic regression model NT-proBNP but not hs-CRP or GGT was significantly associated with three-vessel CAD adjusted for age, sex, ventricular, renal function and classic risk factors (odds ratio = 1.667; 95% CI 1.003 to 2.772; p = 0.049). However, NT-proBNP had no additive predictive value to traditional cardiovascular risk factors for the prediction of angiographically significant CAD in a binary logistic regression model. Conclusions: The predictive value of NT-proBNP for CAD severity is better than that of hs-CRP or GGT. However, NT-proBNP is also of limited value compared with traditional risk factors for predicting significant CAD.

Lack of Association of Soluble CD40 Ligand with the Presence of Acute Myocardial Infarction or Ischemic Stroke in the Emergency Department

BACKGROUND Soluble CD40 ligand (sCD40L) has been proposed as a new risk marker for cardiovascular diseases; however, its possible role as a diagnostic marker in the emergency department (ED) has not yet been investigated. METHODS We investigated sCD40L for the diagnosis of acute myocardial infarction or ischemic stroke in 1089 consecutive patients (525 males, 564 females; age, 17-98 years; median, 56 years) in an ED treating mainly adults with medical or neurologic emergencies. We used a research assay from Roche Diagnostics to measure sCD40L in heparinized plasma prepared from routinely drawn blood samples. RESULTS Intraassay and interassay CVs in our laboratory ranged from 1.6%-4.2% and from 4.4%-4.9%, respectively. A multiple linear regression analysis revealed sCD40L concentration to be significantly associated with C-reactive protein concentration (P = 0.012) and platelet count (P < 0.001). In addition, a subgroup analysis revealed a significant association between smoking and sCD40L concentration (P = 0.006). All other tested variables, including discharge diagnosis, age, sex, and other laboratory variables, showed no significant associations. CONCLUSIONS In adults presenting to the ED, sCD40L is not useful as a diagnostic marker for acute cardiac, cerebrovascular ischemic, or thromboembolic events.

Muscle Trauma and Immune Activation after a Downhill Marathon (Tyrolean Speed Marathon)

Abstract Prolonged physical exercise is associated with multiple changes in the immune status indicating an acute phase response and an activation of the immune system. Eccentric muscle activation (e.g. downhill running) induces micro-trauma of skeletal muscles thus inducing an inflammatory response. At present there are no data to which extent the immune system is activated after a downhill marathon run and if there arc any correlations between immune activation and markers for muscle damage or functional impairment of leg muscles. As model for severe eccentric exercise we selected the Tyrolean Speed Marathon (42 km downhill run, 795 m vertical difference). 13 volunteers (12 male, 1 female; mean running time 224 min [range 193 - 266 min.]) finished the run. Blood from antecubital veins was collected 3-4 days before (T1 ), 3-4 hrs before (T2) and immediately after the marathon (T3) as well as on the morning after the run (T4). We measured serum neopterin concentrations, white blood cell count. C-reactive protein (CRP), creatine kinase (CK), myoglobin (Mb), cardiac troponin I (cTnl) and troponin Τ (cTnT). Moreover, isokinetic muscle tests were performed. Following significant changes were found (before vs. after the run): increase in neopterin, CRP, total leukocyte count, CK. Mb, cTnl, cTnT, whereas isokinetic dynamometry showed a reduction in peak hamstring torque of both thighs after the marathon. There were no significant correlations (Spearmans rank correlation coefficient) between the observed changes in neopterin and CRP, CK, Mb. cTnT, cTnl or between neopterin concentrations and parameters of isokinetic muscle tests. We could demonstrate that a 42 km downhill marathon is associated a) with an activation of the cellular immune system, as evidenced by the increase in serum-neopterin. b) pronounced micro-skeletal muscle damage with high serum creatine kinase and myoglobin, and c) eccentric hamstring fatigue. The absolute changes in neopterin were moderate and similar to other types of exercise (flat course and bicycle marathon, mountain hiking).