Atrial natriuretic peptide concentrations in umbilical cord plasma from pre-eclamptic women

Summary. Atrial natriuretic peptide (ANP) was measured in arterial and venous umbilical cord plasma at the time of delivery by cesarean section in pre-eclamptic (n= 7) and normal women (n= 6). In addition venous samples were obtained from pre-eclamptic (n= 7) and normal pregnant women (n= 7) near term. ANP plasma levels were higher in pregnant women with pre-eclampsia than in normal pregnant women (27·9±4·4 [mean±SEM] and 14·1 ±2·5 pmol 1^-1, respectively, P<0·05). Immediately after delivery plasma ANP in pre-eclamptic mothers was 66·7 ± 12·8 pmol 1^-1 compared to 13·9 ±2·2 pmol 1^-1 in normal mothers (P<0·01). However, in the pre-eclamptic group the levels of ANP in arterial and venous umbilical cord plasma (19·5 ±4·2 and 16·7±4·3 pmol 1^-1 respectively) were significantly (P<0·01) lower than ANP levels in arterial and venous cord plasma (39·6 ± 1·0 and 31·1±4·2 pmol 1^-1, respectively) from normal mothers. It is concluded that the increased ANP plasma level in pre-eclamptic women originates from a maternal source. In addition, since the ANP level is lower in cord plasma than in maternal plasma in pre-eclampsia, fetoplacental volume homeostasis may also be changed in pre-eclampsia.     

Kinetics of 13CO2 elimination after ingestion of 13C bicarbonate: the effects of exercise and acid base balance

Abstract. In order to investigate the effects of muscular work and preceding exercise on the retention of exogenous labelled bicarbonate, we studied the effects of oral administration of [¹³C]bicarbonate (0·1 mg kg^-1) in five subjects at rest before exercise and during and after 1 h of treadmill walking at 73% VO_2max on three separate occasions. Elimination of CO₂ from labelled bicarbonate was 62·6±8·1% at rest, 103·6±11·3% during exercise (P<0·01) and 43·0±4·7% during recovery from exercise (P= 0·01). During exercise mean residence time (MRT) was shorter than at rest (35±7 min vs. 54±9min, P < 0·02) and CO₂ pool size was larger (998±160 ml CO₂kg^-1, vs. 194±28ml CO₂kg^-1, P < 0·001). Compared to values obtained at rest, during recovery from exercise, MRT and CO₂ pool size were reduced (34±5min, P < 0·05; 116±19 ml CO₂kg^-1, P < 0·02, respectively). In an additional five subjects acidosis and alkalosis were induced prior to administration of oral [¹³C]bicarbonate at rest. Elimination of bicarbonate was lower during acidosis (46·1±5·6%, P < 0·01) but was unaltered (50·9±5·6%, NS) during alkalosis, compared to the values obtained at resting pH. During acidosis MRT and CO₂ pool size decreased (37±3min, P<0·01 and 123±10ml CO₂kg^-1, P < 0·01, respectively) whereas in alkalosis MRT was unchanged (65±8 min NS) but CO₂ pool size was increased (230±23ml CO₂kg^-1, P < 0·05). The kinetics of elimination of ¹³CO₂ from administered bicarbonate after exercise are different to those at rest and resemble acidosis. The appropriate correction factor for sequestered ¹³C should be used in metabolic studies of the post-exercise state when using ¹³C tracers.     

Reproducibility of orthostatic changes in cerebral oxygenation in healthy subjects aged 70 years or older

In the elderly, standing can frequently be accompanied by blood pressure (BP) changes and cerebral symptoms such as dizziness, fall, or even syncope, but this may vary from day‐to‐day. Therefore, we aimed to investigate the reproducibility of orthostatic responses of cerebral cortical oxygenation and systemic haemodynamics in elderly subjects. In 27 healthy elderly subjects (age 70–84 years), changes in systolic BP (SBP), diastolic BP (DBP), heart rate (HR) and stroke volume (SV) were continuously monitored by Finapres (Finger Arterial Pressure), and changes in oxyhaemoglobin ([O₂Hb]) and deoxyhaemoglobin ([HHb]) concentrations were continuously measured over the right frontal cortex by near infrared spectroscopy (NIRS) during supine rest and 10 min of active standing on two separate occasions. SBP and DBP increased by 6·7 ± 15·4 mmHg (P<0·05, mean ± SD) and 8·2 ± 6·4 mmHg (P<0·01), respectively, whereas HR increased by 9·5 ± 5·0 bpm (P<0·01) and SV decreased by –8·3 ± 7·4 ml (P<0·01) during standing on the first occasion. [O₂Hb] decreased by –3·9 ± 2·9 μmol l^–1 (P<0·01), while [HHb] increased by 1·8 ± 2·2 μmol l^–1 (P<0·01). Group‐averaged orthostatic changes in cortical oxygenation and systemic haemodynamics were very similar on the two occasions, although an intraindividual variation was found. Cortical oxygenation changes were not accompanied by severe cerebral symptoms. Active standing induced reproducible group‐averaged frontal cortical oxygenation declines in healthy elderly subjects, although an intraindividual day‐to‐day variability was present, possibly related to the variability of orthostatic BP responses. These findings indicate that cerebral autoregulation fails to compensate completely for postural changes in elderly subjects, which might predispose elderly subjects to ischaemic cerebral symptoms.     

Calf vein compliance increases following bed rest after aortocoronary bypass surgery

Early post-operative ambulation (<3 days) is expected to decrease the risk of venous thrombosis, whereas late ambulation (>7 days) increases the risk of orthostatic hypotension. The effect of post-operative bed rest on calf vein compliance was studied before (D ? 1) and 7 days (D + 7) after aortocoronary bypass surgery in 50 patients (41 men and nine women, 65 ± SD 10 years). Calf vein compliance was measured by strain gauge plethysmography and stepwise increases in thigh congestive pressure from 20 to 60 mmHg. Calf compliance [median (25 percentile–75 percentile)] increased significantly by 48% from D ? 1 to D + 7 [0·044 (0·039–0·051) vs. 0·065 (0·048–0·083) ml (100 ml mmHg)^?1, P<0·001]. This increase was reflected as increased calf volume for the 50 mmHg [D ? 1 2·10 (1·75–2·65) vs. D + 7 2·60 (1·70–3·00) ml 100 ml^?1, P<0·01] and 60 mmHg [D ? 1 2·50 (2·10–2·95) vs. D + 7 3·20 (2·30–4·00) ml 100 ml^?1, P<0·001] occlusion pressure levels. The associated pathologies (diabetes and arterial hypertension) and NYHA grades had no significant influence on the increase in compliance. Among the vasoactive therapeutic regimens, calcium channel blockers contributed significantly to the increased calf compliance, but only on D ? 1. The increase in venous compliance following aortocoronary bypass surgery is multifactorial but should be considered for prophylactic management of these patients.     

Osteocalcin metabolism in the pulmonary circulation

The aim of this study was to evaluate the role of the pulmonary vessel endothelium in the removal of circulating osteocalcin, by measuring the osteocalcin levels in serum from pulmonary and radial artery blood from 39 patients undergoing aorto‐coronary bypass. Because of the discrepancies between methods of measurement, two methods were used. Significant differences were observed in group A (n = 18), tested with heterologous radioimmunoassay (2·85 ± 0·67 μg l^?1 in the pulmonary versus 2·69 ± 0·67 μg l^?1 in the radial artery serum, P<0·001) and in group B (n = 21), tested with a two‐site immunoradiometric assay (5·22 ± 1·46 versus 4·93 ± 1·36 μg l^?1, P<0·01). The percentage differences were –5·54 ± 4·76% (P<0·001) in group A and –4·99 ± 8·13% (P<0·01) in group B; the comparison between the percentage differences was not significant. These different osteocalcin concentrations between the two vascular compartments were considered a marker of osteocalcin degradation. Therefore, the study seems to demonstrate that, as well as kidney, liver and bone, the lung is a relevant site of osteocalcin catabolism. The proteolytic activity of pulmonary vessel endothelium seems to involve about 5% of the circulating peptide.     

Inter-relations between the calcium set-points of Parfitt and Brown in primary hyperparathyroidism: a sequential citrate and calcium clamp study

Abstract. The objective of the present study was to compare the calcium set-points of E. M. Brown and A. M. Parfitt obtained by sequential citrate and calcium clamp in patients with primary hyperparathyroidism and healthy controls. Twenty-six patients with primary hyperparathyroidism were investigated and compared to 22 healthy volunteers. All participants were investigated by sequential calcium lowering and raising comprising the following four phases: Phase (1) blood ionized calcium lowering of about 0·20 mmol l^-1; phase (2) steady-state (relative) hypocalcaemia of blood ionized calcium 0·20 mmol l^-1 below baseline; phase (3) blood ionized calcium is raised to about 0·20 mmol l^-1 above baseline; and phase (4) (relative) hypercalcaemia of blood ionized calcium 0·20 mmol l^-1 above baseline. Serum parathyroid hormone (1–84) was measured by an immunoradiometric assay. Blood ionized calcium was measured by a calcium selective electrode. We found the calcium set-points of Parfitt to be 1·42 mmol l^-1 (SD 0·12, n= 52) vs. 1·25 mmol l^-1 (SD 0·04, n= 44) in patients and controls, respectively (P < 0·001). The calcium set-points of Brown were 1·32 mmol l^-1 (SD 0·10, n= 26) vs. 1·13 mmol l^-1 (SD 0·04, n= 22), respectively (P < 0·001). By comparing the calcium set-points of Parfitt and Brown, a strikingly good correlation was observed, in patients (r= 0·91, P < 0·001) and in controls (r= 0·85, P < 0·001). We demonstrate in this paper in vivo that Brown's and Parfitt's calcium set-points are raised in primary hyperparathyroidism and return to normal following parathyroidectomy. The values for Brown's and Parfitt's calcium set-points are significantly different, but strikingly well correlated, supporting the view that Brown and Parfitt describe two different points on the same sigmoidal curve, corresponding to 50% and about 85% inhibition of PTH maximum, respectively. The mathematical form of the sigmoidal curve between blood ionized calcium and parathyroid hormone is very similar in primary hyperparathyroidism and normal humans.     

Standardized submaximal exercise testing in never smokers: a normative study

In a population survey on the south‐western coast of Norway, 373 never smokers aged 18–73 years (230 women) without respiratory symptoms performed a standardized, progressive, incremental submaximal bicycle exercise test. All individuals were able to do an exercise involving oxygen uptake of 1·0 l min^–1, 80% of the subjects reached 1·5 l min^–1 and 50% of the subjects reached 2·0 l min^–1. The respiratory frequency (RF), ventilation (VE) and heart rate (HR) for a given oxygen uptake were all higher in women than in men. Significant predictors of failure to reach oxygen uptake of 1·5 and 2·0 l min^–1 were sex, age, body height and weight. Prediction equations are given for respiratory frequency, heart rate and ventilation for an oxygen uptake of 1·0 l min^–1 in women and 1·5 l min^–1 in men; and body height is a strong predictor for all dependent variables. A multiple linear regression analysis in women showed that age was a significant predictor of respiratory frequency (P<0·05), ventilation (P<0·001) and heart rate (P<0·001), while in men age was a significant predictor only of ventilation (P<0·001) during the bicycle exercise protocol.     

A comparison of dynamic contrast‐enhanced CT and MR imaging‐derived measurements in patients with cervical cancer

This work is to compare the kinetic parameters derived from the DCE‐CT and ‐MR data of a group of 37 patients with cervical cancer. The modified Tofts model and the reference tissue method were applied to estimate kinetic parameters. In the MR kinetic analyses using the modified Tofts model for each patient data set, both the arterial input function (AIF) measured from DCE‐MR images and a population‐averaged AIF from the literature were applied to the analyses, while the measured AIF was used for the CT kinetic analysis. The kinetic parameters obtained from both modalities were compared. Significant moderate correlations were found in modified Tofts parameters [volume transfer constant(K^trans) and rate constant (k_ep)] between CT and MR analysis for MR with the measured AIFs (R = 0·45, P<0·01 and R = 0·40, P<0·01 in high‐K^trans region; R = 0·38, P<0·01 and R = 0·80, P<0·01 in low‐K^trans region) as well as with the population‐averaged AIF (R = 0·59, P<0·01 and R = 0·62, P<0·01 in high‐K^trans region; R = 0·50, P<0·01 and R = 0·63, P<0·01 in low‐K^trans region), respectively. In addition, from the Bland–Altman plot analysis, it was found that the systematic biases (the mean difference) between the modalities were drastically reduced in magnitude by adopting the population‐averaged AIF for the MR analysis instead of the measured ones (from 51·5% to 18·9% for K^trans and from 21·7% to 4·1% for k_ep in high‐K^trans region; from 73·0% to 29·4% for K^trans and from 63·4% to 24·5% for k_ep in low‐K^trans region). The preliminary results showed the feasibility in the interchangeable use of the two imaging modalities in assessing cervical cancers.     

Mesenteric artery response to head-up tilt-induced centralhypovolaemia and hypotension

Superior mesenteric artery (SMA) blood flow and impedance were evaluated byduplex ultrasound during head-up tilt (HUT)-induced central hypovolaemia and hypotension ineight healthy volunteers. HUT induced a reduction in cardiac stroke volume from88·8±6·3 to 64·7±6·3 ml(mean±SEM; P<0·01) and an increase in thoracic electricimpedance from 38·6±2·1 to 42·6±2·1Ω (P<0·01) reflecting a reduced central blood volume. Maintainedtilt provoked a 30% reduction in mean arterial pressure (from 87·1±3·3to 63·4±3·6 mmHg; P<0·01) and the appearanceof presyncopal symptoms. During both the normotensive and the hypotensive phase of HUT, theSMA diameter (5·7±0·03 mm) and blood flow (514±75 ml min^?1) did not change significantly, although the end-diastolic velocity increasedfrom 9·7±4·8 to 39·7±4·0 cm s^?1 (P<0·01). The increase in diastolic velocity, despite amaintained or reduced arterial pressure, supports a reduction in the SMA impedance as it wasreproduced during a meal test when a moderate reduction in mean arterial pressure (87±4to 80±4 mmHg; P=0·04) was accompanied by a ninefoldincrease in the end-diastolic velocity (P<0·01). The results indicate areduction in the mesenteric vascular impedance to the extent that superior mesenteric artery bloodflow is maintained during HUT-induced central hypovolaemia and hypotension.     

Calcium metabolism evaluated by 47calcium-kinetics: a physiological model with correction for faecal lag time and estimation of dermal calcium loss

Summary. Sixty-two calcium balance and ⁴⁷Ca-turnover studies were performed in 51 individuals to evaluate the accuracy and the sensitivity of the methods. The data were analysed according to a modification of the expanding calcium pool model using an improved Bauer-Carlsson-Lindquist (BCL) formulation and an iterative computer procedure. A 7-day whole body retention curve (R₁) combined with a retention curve constructed from excretion data alone (R₂) was used to estimate dermal calcium loss (d) and to demonstrate the significance of individual corrections for delay in faecal excretion (faecal lag time =δt). The mean d was 1–58 mmol Ca/day. The introduction of δt improved the goodness of fit of the data to the model. δt based on ⁴⁷Ca-kinetics was superior to a fixed δt of zero (P < 0·01) or 2 days (P < 0·05). The model derived renal calcium excretion rate was highly correlated (r= 0·98, P < 0·001) to the chemical measured excretion rate. A similar highly significant correlation [Rs= 0·78 (Spearman), P < 0·001] was found between the model derived δt and the carmine red δt. These results indicate a high accuracy of the model. The directly measured parameters showed an excellent reproducibility with a coefficient of variation (CV) less than 4%. The reproducibility of the derived parameters was acceptable (CV = 10–20%) except for the balance (CV = 72%).     

Perfusion heterogeneity does not explain excess muscle oxygen uptake during variable intensity exercise

The association between muscle oxygen uptake (VO₂) and perfusion or perfusion heterogeneity (relative dispersion, RD) was studied in eight healthy male subjects during intermittent isometric (1 s on, 2 s off) one‐legged knee‐extension exercise at variable intensities using positron emission tomography and a‐v blood sampling. Resistance during the first 6 min of exercise was 50% of maximal isometric voluntary contraction force (MVC) (HI‐1), followed by 6 min at 10% MVC (LOW) and finishing with 6 min at 50% MVC (HI‐2). Muscle perfusion and O₂ delivery during HI‐1 (26 ± 5 and 5·4 ± 1·0 ml 100 g^?1 min^?1) and HI‐2 (28 ± 4 and 5·8 ± 0·7 ml 100 g^?1 min^?1) were similar, but both were higher (P<0·01) than during LOW (15 ± 3 and 3·0 ± 0·6 ml 100 g^?1 min^?1). Muscle VO₂ was also higher during both HI workloads (HI‐1 3·3 ± 0·4 and HI‐2 4·1 ± 0·6 ml 100 g^?1 min^?1) than LOW (1·4 ± 0·4 ml 100 g^?1 min^?1; P<0·01) and 25% higher during HI‐2 than HI‐1 (P<0·05). O₂ extraction was higher during HI workloads (HI‐1 62 ± 7 and HI‐2 70 ± 7%) than LOW (45 ± 8%; P<0·01). O₂ extraction tended to be higher (P = 0·08) during HI‐2 when compared to HI‐1. Perfusion was less heterogeneous (P<0·05) during HI workloads when compared to LOW with no difference between HI workloads. Thus, during one‐legged knee‐extension exercise at variable intensities, skeletal muscle perfusion and O₂ delivery are unchanged between high‐intensity workloads, whereas muscle VO₂ is increased during the second high‐intensity workload. Perfusion heterogeneity cannot explain this discrepancy between O₂ delivery and uptake. We propose that the excess muscle VO₂ during the second high‐intensity workload is derived from working muscle cells.     

Plasma lipid and lipoprotein profiles in pre- and post-menopausal middle-aged runners

Summary. Plasma lipid and lipoprotein profiles were compared in middle-aged trained and untrained women before and after menopause. Subjects were assigned to one of four groups: (1) pre-menopausal trained (Pre-T: n= 17, aged 42 ±5 years, body fat 19±5%, training distance 53 ±20 km week^-1, V?o_2max 49 ±4 ml kg^-1 min^-1, mean±SD); (2) pre-menopausal untrained (Pre-UT: n= 26, 42 ±5 years, 24 ±7%, 34 ±6 ml kg^-1 min^-1); (3) post-menopausal trained (Post-T: n= 16, 54 ±3 years, 20 ±4%, 43 ±19 km week^-1, 41 ±5 ml kg^-1 min^-1); and (4) post-menopausal untrained (Post-UT: n= 15, 55 ±3 years, 25 ±6%, 31 ±3 ml kg^-1 min^-1). There were no significant differences in total cholesterol (range 173–194 mg dl^-1), triglyceride (56–72 mg dl^-1), and HDL-cholesterol (HDLC: 76–85 mg dl^-1) among the four groups. LDL-cholesterol (LDLC) in the post-menopausal women (Post-T: 96 ±32 mg dl^-1; Post-UT: 104 ±23 mg dl^-1) tended to be higher than in the premenopausal women (Pre-T: 86 ± 25 mg dl^-1, Pre-UT: 81 ± 23 mg dl^-1). LDLC/HDLC ratio in Post-UT (1·42 ±0·38 unit) was higher than in the pre-menopausal women (Pre-T: 1·03±0·31 unit, P<0·01; Pre-UT: 1·10±0·38 unit, P<0·05), whereas the ratio in Post-T (1·20 ±0·38 unit) was not different from those of the pre-menopausal groups. These results suggest that endurance running protects against the increase in LDLC/HDLC ratio that frequently occurs after menopause.     

Pulmonary vasodilatation and augmentation of right ventricular function following terbutaline infusion in severe chronic pulmonary disease

Summary. Twenty patients with a median age of 61 years and a median forced expired volume in 1 s (FEV₁) after bronchodilatating therapy of 0·55 1 were studied in order to measure the effect of intravenous terbutaline on bronchial tone, cardiac function, pulmonary haemodynamics, gas exchange, and oxygen transport capacity during rest and in 10 patients during exercise. Terbutaline infusion during rest resulted in an increase in heart rate from 84 to 103 beats min^-1 (P < 0·01), a decrease in mean systemic arterial pressure from 95 to 80 mmHg (P < 0·02), an unchanged mean pulmonary arterial pressure (18 mmHg), an increase in cardiac index from 2·89 to 3·86 1 min^-1 m^-2 (P < 0·01), an increase in right ventricular ejection fraction from 45 to 53% (P < 0·01), an increase in left ventricular ejection fraction from 63 to 67% (NS), an unchanged arterial oxygen tension, and an increase in calculated oxygen delivery from 533 to 638 ml O₂ min^-1 m^-2 (P < 0·01). During exercise terbutaline infusion resulted in an increase in heart rate from 108 to 120 beats min^-1 (P < 0·05), a decrease in mean systemic arterial pressure from 117 to 106 mmHg (P < 0·01), a decrease in mean pulmonary arterial pressure from 29 to 22 mmHg (P < 0·01), an increase in cardiac index from 4·53 to 4·64 min^-1 m^-2 (NS), an unchanged arterial oxygen tension, and an increase in the calculated oxygen delivery from 834 to 856 ml O₂ min^-1 m^-2 (NS). It was concluded that terbutaline augments right ventricular function: increases right ventricular ejection fraction and decreases right ventricular end-diastolic volume, and further decreases pulmonary vascular resistance without decreasing arterial oxygen tension, and increases oxygen delivery in patients with chronic pulmonary disease during rest and exercise.     

Diurnal metabolic profiles in hyperthyroidism

Abstract. Hormone and metabolite profiles during a 12 h period of normal meals and activity were examined in nine hyperthyroid subjects with Graves' disease and sixteen matched controls. Six hyperthyroid subjects were restudied when euthyroid on carbimazole and thyroxine. Thyrotoxic patients had mild fasting hyperglycaemia (mean pL SEM blood glucose, 5·5 pL 0·2 v. 4·8 pL 0·1 mmol/l, P < 0·01), elevated blood glycerol (0·15 pL 0·02 v. 0·08 pL 0·01 mmol/l, P < 0·001) and elevated plasma non-esterified fatty acid (NEFA) concentrations (0·91 pL 0·06 v. 0·58 pL 0·03 mmol/l, P < 0·001) when compared to controls. Fasting blood concentrations of the gluconeogenic precursors lactate, pyruvate and alanine, blood ketone body concentrations and circulating insulin and growth hormone levels were similar in hyperthyroid and control subjects. Blood glucose responses to meals were exaggerated and the mean 12 h blood glucose was increased (6·1 pL 0·1 v. 5·5 pL 0·1 mmol/l, P < 0·01) in hyperthyroidism. Similarly, hyperlactataemia and hyperpyruvicaemia were observed after meals. Blood ketone body, blood glycerol and plasma NEFA levels showed exaggerated pre-prandial peaks and the mean 12 h values for blood glycerol (0·12 pL 0·01 v. 0·08 pL 0·01 mmol/l, P < 0·01) and plasma NEFA (0·71 pL 0·03 v. 0·53 pL 0·04 mmol/l, P < 0·01) were increased. Concentrations of insulin and growth hormone remained similar to control values throughout the study period. Blocking therapy with carbimazole and thyroid hormone replacement with thyroxine for 5–10 months suppressed blood glycerol, plasma NEFA and blood ketone body levels to normal or subnormal values but had no effect on the elevated blood glucose, blood lactate or blood pyruvate profiles. Graves' disease with hyperthyroidism is thus associated with abnormalities of carbohydrate metabolism which are not restored to normal by 5–10 months oral antithyroid therapy. The changes in lipid metabolism in hyperthyroidism are normalized by this treatment.     

Studies on kinetics of albumin in uraemic patients on chronic haemodialysis: evidence of interstitial albumin wash-down

Summary. Albumin-kinetic studies were performed in nine uraemic patients without oedema on chronic haemodialysis and in seven normal controls in order to determine microvascular leakiness and thereby, during steady state, lymph drainage of albumin. Transvascular escape rate of albumin [TER_alb, i.e. the fraction of intravascular mass (IVM_alb) passing into, or returning from, the extravascular space per unit time] and the distribution ratio (DR_alb) between IvMalh and total albumin mass were determined from intravenously injected radioiodinated serum albumin. Before haemodialysis, TER_alb was significantly elevated (mean 9·6%IVM_alb h¹, range 5·9–14) as compared to the value 15 h after haemodialysis (mean 7–3, range 5·2–11, P < 0·02) and to controls (mean 5·9, range 4·3–7·4, P < 0·01). Average DR_alb, (mean 0·54, range 0·44–0·69) was clearly elevated in patients with respect to controls (mean 0·44, range 0·42–0·48, P < 0·01), and the extravascular mass of albumin was significantly decreased (mean 27.9 μmol kg¹, range 14·1–41·2 n?. mean 35·9, range 27·1–43·8, P < 0·05). We interpret the results as to indicate increased transvascular filtration of albumin in microcirculatory beds with permeable capillaries (splanchnic organs), in between the haemodialysis treatment, and filtration of protein-poor fluid in areas with ‘tight’ capillaries (skeletal muscle, cutis) resulting in interstitial space protein depletion here. As the patients were considered to be in steady state during the measurements, the increased TER_alh indicates increased lymph flux of albumin. The interstitial space protein ’wash-down’ and increased lymph drainage probably serve as oedema prevention.     

Serum ionized calcium, intact PTH and novel markers of bone turnover in bedridden elderly patients

Abstract. Chronic immobilization could markedly affect calcium and bone metabolism in elderly people. To investigate this, and to test the theory of ‘type II’ osteoporosis in bedridden elderly patients with low vitamin D status, 55 such subjects were examined. Serum concentrations of ionized calcium (Ca⁺⁺), intact parathyrin (PTH) and two novel markers of bone collagen formation (carboxyterminal propeptide of type I procollagen; PICP) and resorption (carboxyterminal crosslinked telopeptide of type I collagen; ICTP) were measured. The effects on these parameters after 40 weeks of supplementation with vitamin D (1000 IU d^-1) and/or calcium (1g d^-1) were subsequently prospectively evaluated. Despite low (mean 11·6 nmol l^-1) serum 25-hydroxyvitamin D levels (25-OHD), those of 1,25-dihydroxy-vitamin D (1,25-(OH)₂D) were mostly normal. Neither correlated with Ca⁺⁺ or PTH. PTH correlated negatively not only with Ca⁺⁺ (r=–0·328, P < 0·05) but also with ICTP (r=–0·306, P < 0·05). Mean PICP was normal but ICTP was elevated and tended to correlate positively with Ca⁺⁺ (r=–0·268, P= 0·06). Vitamin D supplementation did not change PICP or ICTP considerably, despite slightly increased 1,25-(OH)₂D and slightly decreased PTH. Ca⁺⁺ values were normal and remained stable. In conclusion, Ca⁺⁺ and PTH are poor indicators of vitamin D status in chronically immobilized elderly subjects. Furthermore, the results suggest that the increased bone resorption is not due to ‘type II’ secondary hyperparathyroidism; rather the resorption is primarily increased. Correction of vitamin D deficiency does not seem to benefit ageing bones unless adequate mechanical loading is provided.     

Development of troponin autoantibodies in experimental coxsackievirus B3 myocarditis

Background Autoantibodies against various endogenous proteins are found in myocarditis. Troponin autoantibodies are detected in patients with chronic dilated cardiomyopathy, but their presence in myocarditis remains unknown. We set out to study the presence of troponin autoantibodies in experimental viral myocarditis. Materials and methods BALB/c mice infected with coxsackievirus B3 Nancy strain were followed‐up at days 1–7 and 2, 4, 8 and 12 weeks after infection. Levels of circulating cardiac troponin I and circulating troponin autoantibodies were measured. Transthoracic echocardiography was performed. Myocarditis was histopathologically graded and cardiomyocyte apoptosis was quantified (TUNEL). Results Histopathologically relatively mild acute myocarditis followed by persistent cardiomyocyte damage was observed. Rate of cardiomyocyte apoptosis was the highest on day 5 (0·16 ± 0·01% vs. 0·03 ± 0·01% in controls, P < 0·001). Circulating troponin I levels were increased to day 5 (45·2 ± 6·5 ng mL⁻¹, P < 0·005 vs. controls). Troponin autoantibodies were detected from 2 weeks after infection (20% of animals had autoantibodies at 2 weeks, 60% at 4 and 8 weeks and 20% at 12 weeks, P < 0·05 vs. controls). Fractional shortening remained decreased after acute myocarditis (0·36 ± 0·02 at 4 weeks, 0·30 ± 0·02 at 8 and 12 weeks vs. 0·41 ± 0·01 before infection, P < 0·01) parallel to development of troponin autoantibodies. Conclusion Troponin autoantibodies are formed in experimental virus induced myocarditis following troponin I release and cardiomyocyte apoptosis. The definite role of these autoantibodies remains to be further characterized.     

Acute hormonal responses following different velocities of eccentric exercise

The aim of this study was to compare the acute hormonal responses following two different eccentric exercise velocities. Seventeen healthy, untrained, young women were randomly placed into two groups to perform five sets of six maximal isokinetic eccentric actions at slow (30° s^?1) and fast (210° s^?1) velocities with 60‐s rest between sets. Growth hormone, cortisol, free and total testosterone were assessed by blood samples collected at baseline, immediately postexercise, 5, 15 and 30 min following eccentric exercise. Changes in hormonal responses over time were compared between groups, using a mixed model followed by a Tukey's post hoc test. The main findings of the present study were that the slow group showed higher growth hormone values immediately (5·08 ± 2·85 ng ml^?1, P = 0·011), 5 (5·54 ± 3·01 ng ml^?1, P = 0·004) and 15 min (4·30 ± 2·87 ng ml^?1, P = 0·021) posteccentric exercise compared with the fast group (1·39 ± 2·41 ng ml^?1, 1·34 ± 1·97 ng ml^?1 and 1·24 ± 1·87 ng ml^?1, respectively), and other hormonal responses were not different between groups (P>0·05). In conclusion, slow eccentric exercise velocity enhances more the growth hormone(GH) response than fast eccentric exercise velocity without cortisol and testosterone increases.     

Haemodynamic effects of patent foramen ovale and atrial septal defect closure: a comparison during percutaneous shunt closure

Objectives: We investigated the haemodynamic effect of percutaneous closure of an intra‐atrial shunt, using non‐invasive finger pressure measurements. Background: Percutaneous closure of both patent foramen ovale (PFO) and atrial septal defect (ASD) is widely practised. Currently no data are available on short‐term haemodynamic changes induced by closure. Methods: Twenty‐five consecutive patients (mean age 49 ± 17 years, 10 men) who underwent a percutaneous closure of a PFO (n = 15) or ASD (n = 10) were included in this study. During the procedure blood pressure and heart rate (HR) were monitored continuously with a Finometer^®. Changes in systolic, mean, and diastolic pressure, stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were computed from the pressure registrations using Modelflow^® methodology. Results: Baseline characteristics were similar for the PFO and ASD patients. After PFO closure none of the haemodynamic parameters changed significantly. After ASD closure the systolic, mean, and diastolic pressures increased 7·1 ± 5·4 (P = 0·003), 3·8 ± 3·5 (P = 0·007) and 2·0 ± 3·0 mmHg (P = ns) respectively. HR decreased 5·1 ± 5·3 beats per minute (P = 0·01). SV, CO and TPR increased 8·5 ± 6·4 ml (13·5%; P = 0·002), 0·21 ± 0·45 l min^?1 (5·6%; P = ns) and 0·02 ± 0·14 dynes (4·1%; P = ns) respectively. The changes in SV differ between the PFO and ASD patients (P = 0·009). Conclusions: Using non‐invasive finger pressure measurements, we found that SV, mean and systolic blood pressure increased immediately after percutaneous closure of an ASD in adults, whereas the percutaneous PFO closure had no effect on haemodynamic characteristics.     

Hydration status influences the measurement of arterial stiffness

Consensus guidelines have attempted to standardize the measurement and interpretation of pulse wave velocity (PWV); however, guidelines have not addressed whether hydration status affects PWV. Moreover, multiple studies have utilized heat stress to reduce arterial stiffness which may lead to dehydration. This study utilized two experiments to investigate the effects of dehydration on PWV at rest and during passive heat stress. In experiment 1, subjects (n = 19) completed two trials, one in which they arrived euhydrated and one dehydrated (1·2[1·0]% body mass loss). In experiment 2, subjects (n = 11) began two trials euhydrated and in one trial did not receive water during heat stress, thus becoming dehydrated (1·6[0·6]% body mass loss); the other trial subjects remained euhydrated. Using Doppler ultrasound, carotid‐to‐femoral (central) and carotid‐to‐radial (peripheral) PWVs were measured. PWV was obtained at a normothermic baseline, and at a 0·5°C and 1°C elevation in rectal temperature (via passive heating). In experiment 1, baseline central PWV was significantly higher when euhydrated compared to dehydrated (628[95] versus 572[91] cm s^?1, respectively; P<0·05), but peripheral PWV was unaffected (861[117] versus 825[149] cm s^?1; P>0·05). However, starting euhydrated and becoming dehydrated during heating in experiment 2 did not affect PWV measures (P>0·05), and independent of hydration status peripheral PWV was reduced when rectal temperature was elevated 0·5°C (?74[45] cm s^?1; P<0·05) and 1·0°C (?70[48] cm s^?1; P<0·05). Overall, these data suggest that hydration status affects measurements of central PWV in normothermic, resting conditions. Therefore, future guidelines should suggest that investigators ensure adequate hydration status prior to measures of PWV.