[Blood coagulation in normotensives and hypertensives in relation to their body mass index]. / Gerinnung bei Normotonikern und Hypertonikern in Abhängigkeit vom Body Mass Index.

UNLABELLED: BACKGROUND AND PERSPECTIVE: Various parameters of the coagulation cascade and fibrinolysis are important predictors of myocardial infarction and stroke, for which hypertension is a risk factor. It is unclear whether an elevated blood pressure by itself can produce activated clotting. PATIENTS AND METHODS: Coagulation tests were done on overweight hypertensive (n=40); aged 49 +/- 8 years; group 3), overweight normotensives (n=19; aged 51 +/- 8 years; group 2) and normal-weight normotensives (n=20; aged 51 +/- 8; group 1). RESULTS: Plasminogen-activator-inhibitor 1 (PAI-1), a measure of impaired fibrinolysis, was elevated in group 2 (20.5 +/- 11 U/ml; p < 0.001), compared with group 1 (11.6 +/- 6 U/ml), and was even higher in group 3 (27.5 +/- 9 U/ml; p < 0.05). Fibrinogen and factor VIII, parameters that promote clotting, were elevated in group 2 (360 +/- 61 mg/dl and 143 +/- 15 %, respectively; p < 0.001), and in group 3 (368 +/- 63 mg/dl and 146 +/- 18%; p < 0.001) compared to group 1 (304 +/- 40 mg/dl and 127 +/- 17%). Correspondingly, fibrin monometers, a measure of intravascular coagulation, were elevated in group 3 (p < 0.05) and partial thromboplastin time (PTT) decreased (p < 0.001). Pearson correlation showed a significant (p < 0.001) positive relationship between PAI-1 and body mass index (BMI) (0.539), triglycerides (0.512), blood pressure (0.388 to 0.534), fibrinogen (0.404, and a negative one with HDL-cholesterol (0.625). BMI also correlated with fibrinogen (0.509; p < 0.001) and factor VIII (0.337; p < 0.01). CONCLUSIONS: Fibrinolysis and activated coagulation are reduced in hypertensive subjects: this favours the occurrence of myocardial infarction and stroke. In addition to the level of blood pressure, the extent of the changes are effected especially by BMI and metabolic risk factors.

Markers of coagulation, fibrinolysis and angiogenesis after strenuous short-term exercise (Wingate-test) in male subjects of varying fitness levels.

It was the aim of the study to analyse the haemostatic system during a high standardized intensive short-term (30 s) exercise (anaerobic Wingate test). Blood samples were taken from 15 male subjects before (t0 ), and within 2 (t1 ), 9 (t2 ) and 30 min (t3 ) after the test. We found that the partial thromboplastin time was markedly shortened, whereas the prothrombin time increased slightly from t0 to t1 (p < 0.002) and remained elevated (t3, p < 0.046). Factor VIII increased from t0 to t1 (p < 0.001) and remained elevated as well (t3, p < 0.001). Fibrin monomers were approximately 15 times higher immediately post-exercise (t1, p < 0.001) and continued to be elevated (t3, p < 0.004). The tissue plasminogen activator increased by 4 times after exercise (t1, p < 0.001) and remained elevated (t3, p < 0.002). The d-dimers increased from t0 to t1 (p < 0.001) as well and remained elevated (t3, p < 0.005). Thrombopoietin concentrations were unchanged, whereas the vascular endothelial growth factor increased immediately post-exercise (t0 to t1, p < 0.011 resp. at t2 p < 0.019) and returned to the control level at t3 (p < 0.878). In conclusion, it was found that prothrombotic markers and, even more pronounced, those of the fibrinolytic system were increased. The study provides evidence that due to intensive short-term exercise the balance of the haemostatic system is shifted to a higher equilibrium. Theoretically, the data show that in the case of a subject with risk factors such as impaired fibrinolysis, unfavourable conditions cannot be excluded.

Platelet activation through triathlon competition in ultra-endurance trained athletes: impact of thrombin and plasmin generation and catecholamine release.

The aims of this study were to evaluate whether platelets are activated during strenuous exercise in healthy athletes. Also, to determine the impact of plasmin and thrombin activity and catecholamine release. Previous studies have shown activation of the hemostatic system after competitive exercise, but platelet activation was thought to be absent in trained athletes. The impact of thrombin and other potent platelet activators is still a matter for debate. We examined 30 healthy triathletes during a triathlon competition. Flow cytometric detection of CD62p (P-selectin) was used to measure in vivo activation of platelets. Platelet-leukocyte aggregates were also determined. Thrombin concentration was assessed by the thrombin-antithrombin III complex (TAT) and the fibrinolytic state was characterised by the plasmin-alpha2-antiplasmin complex (PAP). Catecholamines were measured by means of high-pressure liquid chromatography. CD62p rose from baseline (2.3%) to 3.4% and was still elevated after 2 hours (3.1%, p = 0.0133). Platelet-leukocyte aggregates were elevated 30 min after exercise (4.3 % vs 3.6%) and decreased significantly after 60 min (2.9 %, p = 0.008). TAT increased from 3.9 microg/l to 8.3 microg/l after competition and to 5.4 microg/l 2 hours later (p < 0.001). PAP increased 10-fold from 350 microg/l to 3,267 microg/l after the triathlon and was still elevated after 2 hours (1,074 microg/l, p<0.001). No linear correlation was found between the hemostatic markers, catecholamines and platelet activation. Platelets, coagulation and fibrinolysis are activated by competitive exercise in athletes, whereby fibrinolytic changes are pronounced. Mechanisms of platelet activation during exercise include phenomena other than plasmatic hemostatic factors and catecholamines.

Activation of blood platelets in response to maximal isometric exercise of the dominant arm.

Isometric exercise is a popular form of physical activity for many people. Only few studies exist on the effects of this type of exercise on the hemostatic system. Eleven male healthy subjects (21-42 years) of varying fitness levels were investigated before, immediately after and 10 min after strenuous isometric exercise of the dominant arm. Blood samples were drawn by repetitive puncture from both the exercising and the contralateral arm. The following variables were studied: Prothrombin time and partial thromboplastin time as group tests for the plasmatic coagulation system; platelet count as well as p-selectin expression for the platelet system; tissue plasminogen activator (t-PA) activity and antigen for the fibrinolytic system. The partial thromboplastin time was shortened immediately after maximal isometric exercise of the dominant arm, the prothrombin time remained unchanged. No change was found in the platelet count, but a marked p-selectin expression was observed immediately after maximal isometric exercise of the dominant arm (p < 0.05) and even in the resting contralateral arm. Values returned to baseline after 10 min. There was a slight increase of t-PA antigen concentration and white blood cell count at maximal isometric contraction which did not occur in the resting arm, although changes over the 3 time points were significant in both arms. Maximal isometric exercise leads to platelet activation in both arms, a slight aPTT decrease and t-PA antigen increase in local blood stream. As compensatory fibrinolytic changes do not occur, it is an open question whether isometric exercise increases the potential risk of thromboembolism.

Vascular endothelial growth factor in exercising humans under different environmental conditions.

It was the aim of this study to investigate the time course of changes in the serum concentrations of vascular endothelial growth factor (VEGF) during a regular survival training programme combined with food and fluid deprivation and during a high altitude marathon run. We studied soldiers of the Austrian Special Forces performing survival training at sea-level and marathon runners of the Posta Atletica who crossed the border between Chile and Argentina at altitudes up to 4722 m. Baseline data collected before the 1-week of survival training showed that the soldiers had normal VEGF [n = 8, 246.7 (SD 118.5) pg.ml(-1)] serum concentrations which remained unchanged during the course of the study. Before the high altitude marathon the subjects showed normal VEGF serum concentrations [178 (SD 84.5) pg.ml(-1)]. After the run VEGF concentrations were found to be significantly decreased [41.0 (SD 41.6) pg ml(-1), P < 0.01]. It was concluded that prolonged physical stress during normobaric-normoxia did not alter the VEGF concentrations whereas during severe hypobaric-hypoxia decreased VEGF serum concentrations were measured, at least temporarily, after prolonged physical exercise which might have been due to changes in production, release, removal and/or binding of circulating VEGF.

Troponin T in patients with low grade or atypical angina. Identification of a high risk group for short- and long-term cardiovascular events.

AIMS: Cardiac troponin T is an established marker of cardiovascular risk in patients with severe angina pectoris. Data are scarce on patients admitted to a coronary care unit with low grade or atypical angina pectoris to rule out myocardial infarction. METHODS AND RESULTS: We investigated 106 patients (57.4 SD 11.6 years) with low grade (Braunwald class I) or atypical symptoms out of 702 patients admitted to the coronary care unit with suspected acute myocardial infarction. Serum concentrations of troponin T were measured at admission and 4 h later. In hospital cardiovascular events including acute myocardial infarction, life threatening cardiac arrhythmias, congestive heart failure, and death were recorded. Patients were additionally observed after 3 and 6 months post-discharge regarding acute myocardial infarction, unstable angina, rehospitalization for cardiac causes and death. The patients were divided into a troponin T positive (> or =0.2 microg x 1(-1) at admission or 4 h later; n=11) and a troponin T negative group. The mean value of troponin T 4 h after admission in the positive group was 0.58 microg x 1(-1). Of the troponin T positive patients, 0.82 (0.95 CI: 0.48-0.98) had a cardiovascular event during their stay in hospital vs 0.41 (0.95 CI: 0.31-0.52) of troponin T negative patients (P<0.05). In the troponin T positive group 0.64 (0.95 CI: 0.31-0.89) developed myocardial infarction in hospital vs 0.07 (0.95 CI: 0.03-0.15) in the troponin T negative group (P<0.001). Troponin T predicts outcome after 3 and 6 months significantly (P<0.05). CONCLUSION: Troponin T identifies patients with low grade or atypical angina at risk of severe short- and long-term cardiovascular events. Therefore, troponin T adds substantial information in patients with ruled out acute myocardial infarction. Troponin T positive patients have to be observed carefully regardless of their symptom intensity and may have to receive early cardiac catheterization; troponin T negative patients could be released safely from the coronary care unit early.

Fluid regulation during prolonged physical strain with water and food deprivation in healthy, trained men.

The aim of this study was to investigate fluidregulating mechanisms, with special regard to the role of plasma proteins in the control of plasma volume (PV), and the role of the superficial tissues as a water storage organ of the body during prolonged physical strain. 29 male subjects (mean age 22.2 +/- 2.8 years) were studied during a 5 day period of survival training with multifactorial strain including restricted water intake (11 H2O.day-1) and food intake (628 kJ.day-1) additionally to physical exercise and sleep deprivation (20 h within 5 days). Under field conditions the heart rate was monitored continuously, and body mass, body composition, thickness of the shell tissues, and blood parameters were measured at (T1), after 72 h (T2), after 120 h (T3) and in the recovery period after 48 h (T4) and 72 h (T5). The estimated energy expenditure was approximately 24,000 kJ.day-1. The mean decrease of body mass was 6.77 kg (9.5%) at T3 (p < 0.001), 0.95 kg (1.3%) at T4 (p < 0.05) and 0.68 kg (0.9%) at T5 (n.s.). A reduction of total body water of 3.8 1 was estimated at T3. Serum creatinine ([Cr]) was raised at T3 by 18.5% (p < 0.0001). No relationship was found between [Cr] and other parameters. The PV decreased by 3.7% (p < 0.0001) at T2, increased by 1.6% (p < 0.0001) at T3 and was not different to baseline at T4 (+0.2%; n.s.). Total protein concentration ([TP]) increased at T2 (11.7%; p < 0.0001) and T3 (2.6%; p < 0.01), and decreased (p < 0.0001) at T4 (8.2%) and T5 (5.7%). Plasma proteins shifted into the intravascular space at T2 and T3 and moved out of the intravascular space at T4 and T5. This gives support to the hypothesis that one of the counterregulatory mechanisms maintaining PV during prolonged exercise is provided by protein shifts from the extravascular into the intravascular space. Our data provide evidence that this mechanism assists PV homeostasis efficiently over a period of 120 h with multifactorial strain, even under conditions with a fluid loss of almost 8% of the total body water.

Erythropoietin in blood volume regulation under real and simulated micro-g conditions.

NASA: Changes in erythropoietin levels in the blood were measured under several experimental conditions. Subjects were exposed to either bedrest, isolation and confinement, head-down tilt, or space flight. Results indicated that production and release of erythropoietin were decreased following simulated weightlessness and in some space flown subjects. The authors conclude that the responses are much more individual in space than during simulation experiments.^ieng

Erythropoietin under real and simulated microgravity conditions in humans.

The aim of this study was to analyze the time course of erythropoietin (EPO) during Earth-bound microgravity simulations such as bed rest, isolation and confinement (IC), head-down tilt (HDT; -6 degrees), and immersion to evaluate which factors could contribute to alterations in EPO under real microgravity conditions during and after short- (< 10 days) and long-term (> 6 mo) spaceflights. During bed rest (24h), no significant changes in EPO could be observed. Subjects confined in a diving chamber facility for 60 days showed a decrease in EPO. In the recovery period a slight increase was observed, but EPO concentrations did not reach the pre-IC control level. In the control period before HDT, subjects showed normal resting values for EPO, but on day 2 of HDT the EPO concentrations were decreased (P < 0.01). Later the EPO levels remained below the control value and were increased after HDT (P < 0.05). After immersion (24 h) increased EPO concentrations could be determined (P < 0.05). During a short-term spaceflight the astronauts showed in-flight (day 4) decreased and unchanged EPO concentrations. During a long-term spaceflight, 24 h after recovery, the cosmonaut showed slightly elevated EPO concentration, which increased markedly during the following days. It is concluded that 1) HDT (-6 degrees) causes a rapid decrease in EPO in humans, 2) IC per se leads to diminished EPO concentrations, 3) EPO regulation in humans during short- and long-term spaceflights might be different, 4) changes in central blood volume, i.e., central venous pressure, seem to be involved in the modulation of EPO production and release under simulated and real microgravity conditions, and 5) the HDT (-6 degrees) Earth-bound simulation reflects mostly the changes in EPO production and release observed under real microgravity conditions in humans.

Shift working in the Chilean Andes (> 3,600 m) and its influence on erythropoietin and the low-pressure system.

It was hypothesized that, in shift workers with a history of intermittent hypoxic stress (working 10 days at > 3,600 m, then resting for 4 days at sea level) for > 5 yr, the initial erythropoietin (EPO) response and the changes in central venous pressure (CVP) are different from those in Caucasian lowlanders. We studied the kitchen personnel (n = 11) of a mine (3,600 m) and a group of Caucasian lowlanders (n = 5). Blood samples were taken, and CVP was determined several times before, during, and after a typical shift. At baseline data collection (BDC) before transition, the shift workers had EPO concentrations of 5.2 +/- 2.4 mU/ml, which increased at altitude (P < 0.01) and returned to BDC values on the recovery (day 16). The Caucasians showed the same time course. Serum transferrin receptor concentrations did not change in either group. CVP values were generally higher in the shift workers than in the Caucasians. In conclusion, the hypothesis that the initial EPO response to a hypoxic stimulus is altered in these shift workers has to be refuted. Higher hemoglobin concentrations and/or CVP values in shift workers might be responsible for the rather low EPO concentrations in shift workers at BDC.

Influence of maximal ergometric exercise on endothelin concentrations in relation to molecular markers of the hemostatic system.

The effects of moderate 30 min cycle ergometer exercise (aerobic metabolism; 0.85-3.71 mmol.1(-1) lactate) followed by short-term exercise at maximal capacity (anaerobic metabolism; 5.09 to 17.75 mmol.1(-1) lactate) on endothelin (ET) and hemostatic variables (tissue plasminogen activator [t-PA] antigen, prothrombin fragments [F1,2], thrombin-antithrombin III complex [TAT], prothrombin time and partial thromboplastin time) were investigated in 15 male healthy subjects of varying fitness levels. Endothelin was measured twice before and immediately after maximal cycle exercise. The results show an increase in endothelin concentration [10.0 pg.ml-1 (baseline) + 6.1 pg.ml-1 (increase post exercise)]. ET did not increase under control conditions. Moderate 30 min exercise caused an increase in t-PA antigen concentration (3.66 + 3.15 ng.ml-1) and short-term maximal exercise produced a markedly higher elevation in this variable (+10.6 ng.ml-1). F1,2 increased (810 + 40 pmol.l-1) under moderate and by 150 pmol.l-1 under anaerobic exercise. TAT increased only at maximal exercise levels (1.01 + 0.32 ng.l-1). No changes were found in any of these variables under control conditions. No correlation of endothelin and the hemostatic variables was found. It is concluded that endothelin and hemostatic markers increase independently during moderate and maximal exercise.

Erythropoietin in 29 men during and after prolonged physical stress combined with food and fluid deprivation.

The study investigated the influence of prolonged physical stress during survival training with food and fluid deprivation on the serum concentrations of erythropoietin (EPO). A group of 29 male subjects [mean age 22.2 (SD 2.8) years, height 1.78 (SD 0.06) m, and body mass (m(b)) 73.5 (SD 8.6) kg] were studied for 5 days of multifactorial stress including restricted water intake (11 H2O. day(-1)) and food intake (628 kJ. day(-1)) combined with physical exercise (estimated energy expenditure approximately 24000 kJ.day(-1)) and sleep deprivation (20 h within 5 days). Blood samples were taken before (T1), after 72 h (T2) and 120 h (T3) of physical stress, and after 48 h, (T4) and 72 h (T5) of recovery. The samples were analysed for EPO, and concentrations of serum iron (Fe), haptoglobin (Hapto), transferrin (Trans), ferritin (Fer), haemoglobin (Hb) and packed cell volume (PCV). The m(b) had decreased by 6.77 kg at T3 (P <0.01) and 0.68 kg at T5. The EPO and Hapto decreased during the survival training (P <0.01) and increased during the recovery period (P <0.01). The Fe increased during the survival training (P <0.01) and remained above the control concentrations during recovery (P <0.01). The Hapto decreased during the survival training (P <0.01) and remained below control concentration at T4 and T5 (P <0.01). The Trans decreased continuously over the week (P <0.01). The Fer increased during the survival training (P <0.01) and returned to control concentration at T5. The Hb increased from T1 to T2 (P <0.01) and had decreased significantly at T5 (P <0.01). The PCV increased from T1 to T2 (P <0.01) and remained below control levels afterwards (P <0.01). From our study it was concluded that, in humans, prolonged physical stress with food and fluid deprivation induces a marked EPO decrease, which is followed by a rapid increase during recovery to restore the reduced O2 transport capacity.

Body weight and body composition during sixty days of isolation.

The aim of this study was to find the mechanisms leading to the weight changes that have frequently been observed during isolation and in spaceflight. Isolation studies with small groups impose limitations on the measurements that can be performed to simple, noninvasive methods. In this study the simple parameters of body weight and body composition, along with sodium and potassium excretion, were determined in three males and one female subject before, during and after 60 days of isolation. Our assumption was that application of these simple methods might provide valuable information, when measurements are done on a daily basis and when the pre- and post-isolation periods are taken into account. Three subjects gained weight before isolation, while one lost weight. All four subjects gradually lost weight during isolation, 1-4% of their weight on the first day of isolation. During the first post-isolation week weight remained stable. During isolation one subject lost body fat, whereas another lost body water and lean body mass, but gained body fat. The urinary electrolyte excretion pattern reflected the changes in body composition: sodium loss coincided with a decrease of total body water, and potassium loss with a decrease of lean body mass. The Bioelectrical Impedance Analysis method, used in defining changes in body composition, provided data in good agreement with those obtained with the double-labeled water method. The results reported here are in agreement with observations reported by other investigators with respect to the body weight changes and the body composition. However, it is still not understood why some subjects lose fat and others gain fat under identical conditions. Psychological factors may be involved in these individual differences. Two further points have become clear from these studies: (1) the pre- and post-isolation periods should be taken into account, (2) urinary electrolyte excretion must be seen in the context of changes in body composition, not only in the context of kidney function.

Renal and endocrine responses in humans to isotonic saline infusion during microgravity.

It was the purpose of this study to investigate how the endocrine and renal mechanisms of fluid volume control in humans (n = 4) adapt to microgravity by applying an intravenous isotonic saline infusion. The acute ground-based supine (Sup) and seated (Seat) positions were chosen as references. During microgravity, renal sodium excretion (UNaV) was doubled during the second and third hours after infusion compared with during Seat (P < 0.05) but blunted during the first hour after infusion compared with during Sup, leading to a reduction in cumulative UNaV (59 +/- 15 vs. 108 +/- 12 mmol/5 h; P < 0.05). Plasma norepinephrine (NE) attained the highest value 3 h after infusion during microgravity (31 +/- 5 x 10(-2) ng/ml vs. 19 +/- 1 and 13 +/- 3 x 10(-2) ng/ml for Seat and Sup, respectively; P < 0.05). Inflight levels of plasma renin and aldosterone were very similar to levels during Seat. In conclusion, 1) the microgravity-adapted renal responses to infusion reflected a condition in between that of ground-based Seat and Sup, respectively, and 2) the plasma levels of NE, renin, and aldosterone were elevated inflight and not related to the changes in UNaV and urinary flow rate. These observations are in contrast to results of ground-based simulation experiments and might partly have been caused by a prior inflight reduction in extracellular fluid volume. The high levels of NE during microgravity warrant further investigation.

[Stress reduction through listening to music: effects on stress hormones, hemodynamics and mental state in patients with arterial hypertension and in healthy persons]. / Stressreduktion durch Musikhören. Einfluss auf Stresshormone, Hämodynamik und psychisches Befinden bei Patienten mit arterieller Hypertonie und bei Gesunden.

Stress hormones, tissue-plasminogen activator (t-PA) antigen, left-ventricular diastolic function and mood immediately before and after listening to three different kinds of music (a waltz by J. Strauss, a piece of modern classic by H. W. Henze, and meditative music by R. Shankar) were measured in 20 healthy persons (10 women, 10 men; mean age 25 [20-33] years) and 20 hypertensives (8 women, 12 men; mean age 57.5 [25-72] years). To recognise haemodynamic effects, mitral flow by Doppler ultrasound was used as a measure of left-ventricular diastolic function. Atrial filling pressure (AFF) was calculated from the flow integral (VTI) of the early E and the late A waves. The Zerssen scale was used to estimate the immediate mood of the subjects. In hypertensives the levels of cortisol (74 vs 78 ng/ml; P < 0.05) and t-PA antigen (4.3 vs 4.5 ng/ml; P < 0.05) were lower after than before the Strauss waltz. The muscle by Henze lowered the concentrations of cortisol (70 vs 84 ng/ml; P < 0.05), noradrenaline (203 vs 224 ng/l; P < 0.05) and t-PA antigen (4.1 vs 4.6 ng/ml; P < 0.05). After listening to the piece by Shankar the concentrations of cortisol (71 vs 78 ng/ml; P < 0.05), adrenaline 14.5 vs 24.5 ng/ml; P < 0.05) and t-PA antigen (4.2 vs 4.3 ng/ml; P < 0.05) were lower. In healthy subjects AFF (29 vs 26%; P < 0.05) rose after the Strauss music, VTI-E fell (69 vs 73 mm; P < 0.05, while natriuretic peptide rose (63 vs 60 pg/ml; P < 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Fluid distribution and tissue thickness changes in 29 men during 1 week at moderate altitude (2,315 m).

To quantify fluid distribution at a moderate altitude (2,315 m) 29 male subjects were studied with respect to tissue thickness changes [front (forehead), sternum, tibia], changes of total body water, changes of plasma volume, total protein concentrations (TPC), colloid osmotic pressure (COP), and electrolytes. Tissue thickness at the forehead showed a significant increase from 4.14 mm to 4.41 mm 48 h after ascent to the Rudolfshuette (2,315 m) (P < 0.05). At 96 h after ascent the tissue thickness at the tibia was decreased to 1.33 mm compared to the control value of 1.59 mm (P < 0.01). Body mass increased from 75.5 kg (control) to 76.2 kg on the last day (P < 0.05) and body water from 44.21 to 45.01 during the week (P < 0.01). The accumulation fluid in the upper part of the body was paralleled by a decrease in TPC and COP. At 48 h after the ascent COP dropped from 29.5 mmHg to 27.5 mmHg (P < 0.01). After 96 h at moderate altitude COP was still significantly decreased compared to the control level. At 1.5 h after the return from the Rudolf-shuette in Saalfelden (744 m) COP was back to the control values. The TPC also showed an initial drop from 7.75 g.dl-1 to 7.48 g.dl-1 after 48 h at altitude and remained below the control value during the whole week (P < 0.01). It seems from our study that even with exposure to moderate altitude measurable fluid shifts to the upper part of the body occurred which were detected by our ultrasound method.