Autonomic nervous function at rest in aerobically trained and untrained oldermen

Therelationship between aerobictraining, vagal influence on the heart and ageing was examined by assessing aerobic fitness andresting heart rate variability in trained and untrained older men. Subjects were 11 trained cyclistsand runners (mean age=6±61·6 years) and 11 untrained, age-matchedmen (mean age=66±1·2 years). Heart rate variability testing involvedsubjects lying supine for 25 min during which subjects’ breathing was paced andmonitored (7·5 breaths min^?1). Heart rate variability was assessedthrough time series analysis (HRV_ts) of the interbeat interval. Results indicated thattrained older men (3·55±0·21 l min^?1) hadsignificantly (P<0·05) greater VO _2maxthan that of control subjects (2·35±0·15 l min^?1).Also, trained older men (52±1·8 beats min^?1) hadsignificantly (P<0·05) lower supine resting heart rate than that of controlsubjects (65±4·2 beats min^?1). HRV_ts at highfrequencies was greater for trained men (5·98±0·22) than for untrainedmen (5·23±0·32). These data suggest that regular aerobic exercise inolder men is associated with greater levels of HRV_ts at rest.     

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.     

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.     

Postoperative volume balance: does stroke volume increase in Trendelenburg's position?

In healthy humans, stroke volume (SV) and cardiac output (CO) do not increase with expansion of the central blood volume by head-down tilt or administration of fluid. Here, we exposed 85 patients to Trendelenburg's position about one hour after surgery while cardiovascular variables were determined non-invasively by Modelflow. In Trendelenburg's position, SV (83 ± 19 versus 89 ± 20 ml) and CO (6·2 ± 1·8 versus 6·8 ± 1·8 l/min; both P<0·05) increased, while heart rate (75 ± 15 versus 76 ± 14 b min⁻¹) and mean arterial pressure were unaffected (84 ± 15 versus 84 ± 16 mmHg). For the 33 patients (39%) with a > 10% increase in SV (from 78 ± 16 to 90 ± 17 ml) corresponding to an increase in CO from 5·9 ± 1·5 to 6·9 ± 1·6 l min⁻¹ (P<0·05) when tilted head-down, administration of 250 ml Ringer's lactate solution increased SV (to 88 ± 18 ml) and CO (to 6·8 ± 1·7 l min⁻¹). In conclusion, determination of SV and/or CO in Trendelenburg's position can be used to evaluate whether a patient is in need of IV fluid as here exemplified after surgery.     

Circulatory response to single circuit weight and walking training sessions of similar energy cost in middle‐aged overweight females

The aim of this study was to compare circulatory responses to circuit weight (CWT) and aerobic walking training sessions of similar energy cost in middle‐aged overweight females. Thirty‐three middle‐aged pre‐menopausal females participated in the experiment. They were divided into overweight (n=18, 36·2 ± 6·3 years, 166·3 ± 8·0 cm, 83·5 ± 9·7 kg, BMI 30·2 ± 3·1 kg m^–2) and non‐overweight control (n=15, 34·1 ± 6·3 years, 165·0 ± 5·6 cm, 61·6 ± 5·0 kg, BMI 22·7 ± 1·5 kg m^–2) groups. Individual physical working capacity (PWC) was measured using the cycle ergometer test (calculated at the level of predicted HR_max (205 – ½ age). A CWT session consisted of leg extension, bench press, sit‐ups and leg press exercises. The subjects performed four circuits at the maximal possible speed, using a work‐to‐rest ratio of 60 s. Blood pressure (BP) was measured during every rest period between the exercises, and the heart rate (HR) was recorded continuously during the whole CWT programme. During the walking training session, the subjects walked as fast as possible on the indoor track. The total energy cost of the walking training session was the same as during the CWT session, approximately 270 kcal, and was controlled by a CALTRAC accelerometer. HR and BP were measured every 5 min during the walking training session. The PWC index was significantly (P<0·05) higher in the overweight group in comparison with the control females (215·4 ± 76·1 and 187·9 ± 42·4 W, respectively). The resting BP was normal in both groups (<140/90 mmHg). HR was between 120 and 140 beats min^–1 during CWT and walking sessions. There were no differences in BP during both training sessions in overweight and control subjects. It was concluded that both CWT and walking training sessions were acceptable forms of physical activity to increase cardiovascular fitness in middle‐aged overweight and normal body weight females.     

Impact of antiretroviral therapy on visfatin and retinol-binding protein 4 in HIV-infected subjects

Background To determine circulating levels of adipocytokines, especially the recently characterized visfatin, and the fat‐derived factor retinol‐binding protein‐4 (RBP‐4) in HIV‐infected subjects and their respective changes following treatment with highly active antiretroviral therapy (HAART). Materials and methods Fourteen HIV‐positive, HAART‐naïve subjects were compared with 10 HIV‐negative healthy controls and reassessed after a 1‐year treatment with HAART. Plasma visfatin and RBP‐4 were determined by ELISA, whereas leptin and adiponectin by RIA. Body composition was measured with dual X‐ray absorptiometry (DXA). Homeostasis model assessment (HOMA‐IR) was assessed using insulin and glucose levels. Results Visfatin and RBP‐4 levels in HIV‐positive subjects were comparable with those of HIV‐negative controls before treatment with HAART. Treatment with HAART for 12 months resulted in a 6·9‐fold and 7·1‐fold increase of visfatin and RBP‐4 levels (+54·0 ± 9·7 ng mL^?1, P < 0·0001 and +95·3 ± 31·7 ng mL^?1, P < 0·01), respectively. Leptin (?2·7 ± 1·6 ng mL^?1, P = 0·054) was unchanged and adiponectin (?2·8 ± 0·7 µg mL^?1, P < 0·01) decreased. Changes of visfatin concentrations correlated significantly with the increases of RBP‐4 (r = 0·78, P = 0·001), fat‐free mass (FFM, r = 0·75, P < 0·05) and change of HOMA‐IR (r = 0·64, P < 0·05). Parameters of glucose metabolism and body fat mass were unchanged during the observation period. Conclusions Treatment with HAART induced a pronounced increase of plasma visfatin and RBP‐4 as well as a decrease of adiponectin in HIV‐infected patients on HAART. Although body weight, fat mass and parameters of glucose metabolism remained stable, the changes in the adipocytokines might herald subsequent alterations of these parameters.     

Simultaneous quantification of myocardial perfusion,oxidative metabolism,cardiac efficiency and pump function at rest and during supine bicycle exercise using 1‐11C‐acetate PET – a pilot study

Background: PET using 1‐¹¹C‐acetate (ACE‐PET) applied at rest is used for measuring absolute myocardial blood flow (MBF) and oxidative metabolic rate (k_mono). We evaluated the feasibility of quantitative ACE‐PET during exercise. Methods: Five endurance athletes underwent dynamic PET scanning at rest and during supine bicycle stress. Exercise was maintained at a workload of 120 Watt for 17 min. The rate‐pressure product (RPP) was recorded repeatedly. MBF, k_mono in left (LV) and right (RV) ventricular wall, cardiac output (CO), cardiac efficiency and a lung uptake value reflecting left heart diastolic pressures were calculated from the PET data using previously validated models. Results: MBF increased from 0·71 ± 0·17 to 2·48 ± 0·25 ml min^?1 per ml, LV‐k_mono from 0·050 ± 0·005 to 0·146 ± 0·021 min^?1, RV‐k_mono from 0·023 + 0·006 to 0·087 + 0·014 min^‐1, RPP from 4·7 ± 0·8 to 13·2 ± 1·4 mmHg × min^?1 × 10³ and Cardiac Output from 5·2 ± 1·1 to 12·3 ± 1·2 l min ^?1 (all P < 0·001). Cardiac efficiency was unchanged (P = 0·99). Lung uptake decreased from 1·1 ± 0·2 to 0·6 ± 0·1 ml g^?1 (P < 0·001). Discussion: A number of important parameters related to cardiac function can be quantified non‐invasively and simultaneously with a short scanning protocol during steady state supine bicycling. This might open up new opportunities for studies of the integrated cardiac physiology in health and early asymptomatic disease.     

Restoration of peak vascular conductance after simulated microgravity by maximal exercise

We sought to determine if (i) peak vascular conductance of the calf was reduced following prolonged exposure to simulated microgravity, and (ii) if maximal cycle ergometry performed at the end of microgravity exposure stimulated a restoration of peak calf vascular conductance. To do this, peak vascular conductance of the calf was recorded following ischaemic plantar flexion exercise to fatigue in seven men after 16 days of head-down tilt (HDT) under two conditions: (i) after one bout of maximal supine cycle ergometry completed 24 h prior to performance of ischaemic plantar flexion exercise, and (ii) in a control (no cycle ergometry) condition. Following HDT, peak vascular conductance was reduced in the control condition (0·38 ± 0·02 to 0·24 ± 0·02 ml 100 ml^?1 min^?1 mmHg^?1; P = 0·04), but was restored when subjects performed cycle ergometry (0·33 ± 0·05 to 0·28 ± 0·04 ml 100 ml^?1 min^?1 mmHg^?1; P = 0·46). After HDT, time to fatigue during ischaemic plantar flexion exercise was not different from pre-HDT 24 h after performance of exhaustive cycle ergometry (120 ± 24 vs. 122 ± 19 s), but was decreased in the control condition (116 ± 11 vs. 95 ± 8 s; P = 0·07). These data suggest that a single bout of maximal exercise can provide a stimulus to restore peak vascular conductance and maintain time to fatigue during performance of ischaemic plantar flexion exercise.     

Effect of beta blockade with and without sympathomimetic activity (ISA) on sympathovagal balance and baroreflex sensitivity

Beta blockers increase heart rate variability (HRV) and improve survival in coronary artery disease (CAD). The benefit of beta blockers with intrinsic sympathomimetic activity (ISA) in CAD still remains a matter of debate, and their effect on HRV has not yet been investigated. Therefore, we measured HRV, systolic blood pressure variability (BPV) and baroreflex sensitivity (BRS) under propranolol (PROP, without ISA, 160 mg q.d.), pindolol (PIN, with potent ISA, 15 mg q.d.) and placebo (PLA, q.d.) in 30 healthy subjects, aged 21–39 years, during controlled frequency breathing (0·30 Hz) in supine and tilt positions. PROP increased HRV in the high-frequency (0·15–0·40 Hz) band (PROP 7·4 ± 1·0; PLA 6·9 ± 1·4; PIN 6·8 ± 1·0 ln MI²; P = 0·003), decreased BPV in the low-frequency band (at 0·1 Hz, Mayer waves) (PROP 0·6 ± 0·7; PLA 1·3 ± 1·1; PIN 1·2 ± 1·2 ln mmHg²; P = 0·001) and enhanced BRS (PROP 14·6 ± 9·5; PLA 8·0 ± 6·8; PIN 8·7 ± 6·8 ms mmHg^?1; P = 0·001) in the supine position. After passive tilt, PROP decreased HRV in the low-frequency band (PROP 6·1 ± 0·9; PLA 6·5 ± 1·1; PIN 6·9 ± 0·7 ln MI²; P<0·001) and decreased Mayer waves (PROP 1·8 ± 0·8; PLA 2·4 ± 1·0; PIN 2·7 ± 0·8 ln mm Hg²; P<0·001). PIN increased the low-frequency HRV response, which is induced by passive tilt (PIN + 0·9 ± 1·0; PLA + 0·3 ± 1·3, PROP + 0·3 ± 1·0 ln MI²; P = 0·026). Our results prove that beta-adrenergic blockade with potent ISA does not increase HRV, has no beneficial effect on autonomic balance and even exaggerates sympathetic responses to passive tilt.     

Intensity of Nordic Walking in young females with different peak O2 consumption

The purpose of this cross‐sectional study was to determine the physiological reaction to the different intensity Nordic Walking exercise in young females with different aerobic capacity values. Twenty‐eight 19–24‐year‐old female university students participated in the study. Their peak O₂ consumption (VO₂ peak kg^?1) and individual ventilatory threshold (IVT) were measured using a continuous incremental protocol until volitional exhaustion on treadmill. The subjects were analysed as a whole group (n = 28) and were also divided into three groups based on the measured VO₂ peak kg^?1 (Difference between groups is 1 SD) as follows: 1. >46 ml min^?1 kg^?1 (n = 8), 2. 41–46 ml min^?1 kg^?1 (n = 12) and 3. <41 ml min^?1 kg^?1 (n = 8). The second test consisted of four times 1 km Nordic Walking with increasing speed on the 200 m indoor track, performed as a continuous study (Step 1 – slow walking, Step 2 – usual speed walking, Step 3 – faster speed walking and Step 4 – maximal speed walking). During the walking test expired gas was sampled breath‐by‐breath and heart rate (HR) was recorded continuously. Ratings of perceived exertion (RPE) were asked using the Borg RPE scale separately for every 1 km of the walking test. No significant differences emerged between groups in HR of IVT (172·4 ± 10·3–176·4 ± 4·9 beats min^?1) or maximal HR (190·1 ± 7·3–191·6 ± 7·8 beats min^?1) during the treadmill test. During maximal speed walking the speed (7·4 ± 0·4–7·5 ± 0·6 km h^?1) and O₂ consumption (30·4 ± 3·9–34·0 ± 4·5 ml min^?1 kg^?1) were relatively similar between groups (P > 0·05). However, during maximal speed walking, the O₂ consumption in the second and third groups was similar with the IVT (94·9 ± 17·5% and 99·4 ± 15·5%, respectively) but in the first group it was only 75·5 ± 8·0% from IVT. Mean HR during the maximal speed walking was in the first group 151·6 ± 12·5 beats min^?1, in the second (169·7 ± 10·3 beats min^?1) and the third (173·1 ± 15·8 beats min^?1) groups it was comparable with the calculated IVT level. The Borg RPE was very low in every group (11·9 ± 2·0–14·4 ± 2·3) and the relationship with VO₂and HR was not significant during maximal speed Nordic Walking. In summary, the present study indicated that walking is an acceptable exercise for young females independent of their initial VO₂ peak level. However, females with low initial VO₂ peak can be recommended to exercise with the subjective ‘faster speed walking’. In contrast, females with high initial VO₂ peak should exercise with maximal speed.     

Sympathetic activation during the cold pressor test: influence of stimulus area

Summary. The purpose of this study was to determine the effect of the size of the stimulus area on the muscle sympathetic nerve activity (MSNA), systolic arterial blood pressure (SAP), and heart rate responses to the cold pressor test. To accomplish this, these variables were measured before (control), during, and after 1·5 min of ice water immersion of either one or both hands in nine healthy subjects (aged 19–27 years). The cold stimulus elicited significant increases above control levels in all three variables under both conditions (P<0·05). Immersion of both hands produced a much greater increase in total MSNA (+366%) than immersion of a single hand (+187%) (P<0·05). However, the magnitudes of the increases in SAP and heart rate during two-hand immersion (29±6 mmHg and 10±2 beats min^-1) were not significantly different from the responses during the one-hand trials (24±5 mmHg and 6±2 beats min^-1, P>0·05). There was a strong, direct relationship between total MSNA and SAP responses during one-hand immersion (r= 0·93, P<0·001) but not during immersion of both hands (r= 0·66, P= 0·08). These findings indicate that during the cold pressor test the magnitude of the increase in sympathetic discharge to skeletal muscle, but not the systolic blood pressure response, is influenced by the size of the tissue area exposed to the stimulus.     

Determination of baroreflex gain using auto-regressive moving-average analysis during spontaneous breathing

The heart rate component of the arterial baroreflex gain (BRG) was determined with auto-regressive moving-average (ARMA) analysis during each of spontaneous (SB) and random breathing (RB) protocols. Ten healthy subjects completed each breathing pattern on two different days in each of two different body positions, supine (SUP) and head-up tilt (HUT). The R–R interval, systolic arterial pressure (SAP) and instantaneous lung volume were recorded continuously. BRG was estimated from the ARMA impulse response relationship of R–R interval to SAP and from the spontaneous sequence method. The results indicated that both the ARMA and spontaneous sequence methods were reproducible (r=0·76 and r=0·85, respectively). As expected, BRG was significantly less in the HUT compared to SUP position for both ARMA (mean ± SEM; 3·5 ± 0·3 versus 11·2 ± 1·4 ms mmHg^–1; P<0·01) and spontaneous sequence analysis (10·3 ± 0·8 versus 31·5 ± 2·3 ms mmHg^–1; P<0·001). However, no significant difference was found between BRG during RB and SB protocols for either ARMA (7·9 ± 1·4 versus 6·7 ± 0·8 ms mmHg^–1; P=0·27) or spontaneous sequence methods (21·8 ± 2·7 versus 20·0 ± 2·1 ms mmHg^–1; P=0·24). BRG was correlated during RB and SB protocols (r=0·80; P<0·0001). ARMA and spontaneous BRG estimates were correlated (r=0·79; P<0·0001), with spontaneous sequence values being consistently larger (P<0·0001). In conclusion, we have shown that ARMA-derived BRG values are reproducible and that they can be determined during SB conditions, making the ARMA method appropriate for use in a wider range of patients.     

Anatomical vertebral artery hypoplasia and insufficiency impairs dynamic blood flow regulation

Recent studies have suggested that vertebral artery (VA) hypoplasia is a predisposing factor for posterior cerebral stroke. We examined whether anatomical vertebrobasilar ischemia, i.e., unilateral VA hypoplasia and insufficiency, impairs dynamic blood flow regulation. Twenty‐eight female subjects were divided into three groups by defined criteria: (i) unilateral VA hypoplasia (n = 8), (ii) VA insufficiency (n = 6), and (iii) control (n = 14). Hypoplastic VA criterion was VA blood flow of 40 ml min^?1, whereas VA insufficiency criterion was net (left + right) VA blood flow of 100 ml min^?1 or less. We evaluated left, right, and net VA blood flows by ultrasonography during hypercapnia, normocapnia, and hypocapnia to evaluate VA CO₂ reactivity. The unilateral VA hypoplasia group showed lower CO₂ reactivity at hypoplastic VA than at non‐hypoplastic VA (2·65 ± 0·58 versus 3·00 ± 0·48% per mmHg, P = 0·027) and net VA CO₂ reactivity was preserved (Unilateral VA hypoplasia, 2·95 ± 0·48 versus Control, 2·93 ± 0·42% per mmHg, P = 0·992). However, the VA insufficiency group showed a lower net VA CO₂ reactivity compared to the control (2·29 ± 0·55 versus 2·93 ± 0·42% per mmHg, P = 0·032) and the unilateral VA hypoplasia (P = 0·046). VA hypoplasia reduced CO₂ reactivity, although non‐hypoplastic VA may compensate this regulatory limitation. In subjects with VA insufficiency, lowered CO₂ reactivity at the both VA could not preserve normal net VA CO₂ reactivity. These findings provide a possible physiological mechanism for the increased risk of posterior cerebral stroke in subjects with VA hypoplasia and insufficiency.     

Cardiac troponin I and ventricular arrhythmia in patients with chronic heart failure

Background Both detectable serum cardiac troponin I (cTnI) and ventricular dysrhythmias are common in patients with chronic heart failure (CHF) and are paralleled with the severity of the CHF. However, the relationship between serum cTnI and ventricular arrhythmia severity in patients with CHF remains unknown; the mechanism of the ventricular arrhythmia in the CHF patients also remains unclear. Materials and methods The study group included 218 patients with CHF who had cTnI assay drawn at the time of initial presentation. Patients with acute myocardial infarction or myocarditis were excluded from the analysis. The patients were divided into two groups: cTnI‐positive with serum cTnI > 0·5 ng mL^?1 (n = 98) and cTnI‐negative with serum cTnI ≤ 0·5 ng mL^?1 (n = 120). The severity of ventricular dysrhythmias was assessed by 24‐h Holter monitoring, using prospectively defined measures of ventricular arrhythmic burden. Results Prevalence of risk factors for ventricular dysrhythmias was equal in both groups. All measures of ventricular ectopy were much higher in patients of the cTnI‐positive groups. Mean hourly ventricular pairs (13·59 ± 10·3 vs. 11·1 ± 6·01, P = 0·027), mean hourly repetitive ventricular beats (26·01 ± 13·67 vs. 22·01 ± 13·56, P = 0·032), and the frequency of ventricular tachycardia episodes per 24 h (12·54 ± 16·68 vs. 7·68 ± 11·54, P = 0·012) were higher in patients with detectable cTnI levels. After inclusion of clinical variables and drug therapies in a multivariate analysis, the positive relationship between cTnI and the frequency of ventricular pairs (P = 0·03), repetitive ventricular beats (P = 0·037), and ventricular tachycardia (P = 0·03) remained independent. In multivariate logistic regression, the risk of developing ventricular tachycardia was higher in patients with detectable cTnI levels with an adjusted odds ratio (OR) of 2·31 (95% CI, 1·22–2·65, P = 0·003). Conclusions In patients with CHF, serum cTnI is closely related to increased occurrence of ventricular dysrhythmias and could identify a subgroup of patients with ventricular tachycardia. The minimal myocardial injury detected by serum cTnI might be the abnormal substrate for ventricular dysrhythmias.     

WNK4 regulates airway Na+ transport: study of familial hyperkalaemia and hypertension

Background WNK [With No K (lysine)] kinases are essential for regulation of blood pressure and potassium homeostasis. WNK4 expression was recently found not only in the distal nephron but also in chloride‐transporting epithelia. To establish a physiological role for this distribution we studied patients with familial hyperkalaemia and hypertension (FHH), [pseudohypoaldosteronism type II (PHAII)], which is caused by mutations in WNK4. Design Measurement of nasal potential difference (NPD) and sweat electrolytes were performed in controls, in six subjects with FHH and ten subjects with cystic fibrosis (CF). Results Basal NPD was higher in FHH compared with controls (n = 20): 22·8 ± 5·7 vs. 16·2 ± 5·3 mV, respectively (P = 0·014). Maximal response to amiloride was also higher in FHH compared with controls: 14·8 ± 3·5 vs. 10·0 ± 4·8 mV, respectively (P = 0·03). In CF these values were 42·9 ± 9·3 and 29·9 ± 7·4 mV, respectively. The kinetics of the amiloride effect were faster in FHH, and as first reported here also in CF, compared with controls. At 30 s, amiloride‐inhibitable residual PD in FHH was 50 ± 30 vs. 81 ± 9% in controls (P = 0·0003) and 56 ± 7% in CF. The response to chloride‐free and isoproterenol solutions, which determines chloride transport activity, was similar in FHH compared with controls [16·0 ± 8·6 vs. 10·4 ± 5·9 mV (P = 0·08)]. Sweat conductivity in FHH was 49·7 ± 7·3 vs. 38·2 ± 8·1 mmol (NaCl eq) L^?1 in 16 controls (P = 0·007) and 94·0 ± 19·3 in CF. Conclusions Mutant WNK4 increases Na⁺ transport in airways, and therefore it is regulated by wild‐type WNK4. This may be caused by a regulation of ENaC or a K⁺ channel.     

The age‐related reduction in cerebral blood flow affects vertebral artery more than internal carotid artery blood flow

Ageing reduces cerebral blood flow (CBF), while mean arterial pressure (MAP) becomes elevated. According to ‘the selfish brain’ hypothesis of hypertension, a reduction in vertebral artery blood flow (VA) leads to increased sympathetic activity and thus increases MAP. In twenty‐two young (24 ± 3 years; mean ± SD) and eleven elderly (70 ± 5 years) normotensive men, duplex ultrasound evaluated whether the age‐related reduction in CBF affects VA more than internal carotid artery (ICA) blood flow. Pulse‐contour analysis evaluated MAP while near‐infrared spectroscopy determined frontal lobe oxygenation and transcranial Doppler middle cerebral artery mean blood velocity (MCA V_mean). During supine rest, MAP (90 ± 13 versus 78 ± 9 mmHg; P<0·001) was elevated in the older subjects while their frontal lobe oxygenation (68 ± 7% versus 77 ± 7%; P<0·001), MCA V_mean (49 ± 9 versus 60 ± 12 cm s^?1; P = 0·016) and CBF (754 ± 112 versus 900 ± 144 ml min^?1; P = 0·004) were low reflected in VA (138 ± 48 versus 219 ± 50 ml min^?1; P<0·001) rather than in ICA flow (616 ± 96 versus 680 ± 120 ml min^?1; P = 0·099). In conclusion, blood supply to the brain and its oxygenation are affected by ageing and the age‐related decline in VA flow appears to be four times as large as that in ICA and could be important for the age‐related increase in MAP.     

Quantification of left ventricular volumes and ejection fraction from gated 99mTc‐MIBI SPECT: MRI validation of the exini heart software package

The aim of the study was to validate the accuracy of the exini heart software (exini ) package in assessing left ventricular end‐diastolic/systolic volumes (EDV, ESV) and ejection fraction (LVEF) from gated ^99mTc‐MIBI single‐photon emission tomography (SPECT). Cardiac magnetic resonance imaging (cMRI) was used as reference. Furthermore, effects of perfusion defects and image quality in SPECT on correlation between gated SPECT and magnetic resonance imaging were investigated. Methods: Seventy patients were examined using gated SPECT (rest study, eight gates per cardiac cycle). EDV, ESV and LVEF were calculated from gated SPECT using exini . Directly before or after SPECT, cMRI (20 gates cardiac per cycle) was performed. EDV, ESV and LVEF were calculated using Simpson’s rule. Perfusion defects were quantified using the summed‐rest‐score (SRS). Total number of myocardial counts were used to rate image quality. Results: Correlation between results of gated SPECT and cMRI was high for EDV (R = 0·89) and ESV (R = 0·94) and good for LVEF (R = 0·78). ESV (exini 54 ± 31 ml versus cMRI 57 ± 34 ml) and LVEF (exini 62·9 ± 11·7% versus cMRI 60·6 ± 13·9%) did not differ significantly whereas exini overestimated EDV significantly compared with cMRI (exini 144 ± 41 ml versus cMRI 137 ± 36 ml; P<0·005). No correlation was found between absolute differences of the results given by gated SPECT and cMRI and SRS or total myocardial counts (R < 0·18). Conclusion: End‐diastolic volume, ESV and LVEF calculated from gated SPECT using exini agree with cMRI over a wide range of values. Correlation between both the methods was good for EDV and ESV, and acceptable for LVEF. No relevant influence of image quality or SRS on the accuracy of exini results was found.     

Longitudinal left ventricular function is globally depressed within a week of STEMI

Sixty percent of stroke volume (SV) is generated by atrioventricular plane displacement (AVPD) in a healthy left ventricle (LV). The aims were to determine the effect of ST‐elevation myocardial infarction (STEMI) on AVPD and contribution of AVPD to SV and to study the relationship between AVPD and infarct size (IS) and location. Patients from CHILL‐MI and MITOCARE studies with cardiovascular magnetic resonance within a week of STEMI (n = 177, 59 ± 11 years) and healthy controls (n = 20, 62 ± 11 years) were included. Left ventricular volumes were quantified in short‐axis images. AVPD was measured in six locations in long‐axis images. Longitudinal contribution to SV was calculated as AVPD multiplied by the short‐axis epicardial area. Patients (IS 17 ± 10% of LV) had decreased ejection fraction (48 ± 8%) compared to controls (60 ± 5%, P<0·001). Global AVPD was decreased in patients (11 ± 2 mm versus 15 ± 2 mm in controls, P<0·001) and this held true for both infarcted and remote segments. AVPD contribution to SV was lower in patients (58 ± 9%) than in controls (64 ± 8%) (P<0·001). There was a weak negative correlation between IS and AVPD (r²=0·06) but no differences in global AVPD linked to infarct location. Decrease in global and regional AVPD occur even in remote myocardium within 1 week of STEMI. Global AVPD decrease is independent of MI location, and MI size has only minor effect. Longitudinal pumping is slightly lower compared to controls but remains to be the main component to SV even after STEMI. These results highlight the difficulty in determining infarct location and size from longitudinal measures of LV function.     

Mannitol clearance for the determination of glomerular filtration rate–a validation against clearance of 51Cr‐EDTA

We studied the agreement between plasma clearance of mannitol and the reference method, plasma clearance of ⁵¹Cr‐EDTA in outpatients with normal to moderately impaired renal function. Forty‐one patients with a serum creatinine <200 μmol l^?1 entered the study. ⁵¹Cr‐EDTA clearance was measured with the standard bolus injection technique and glomerular filtration rate (GFR) was calculated by the single‐sample method described by Jacobsson. Mannitol, 0·25 g kg^?1 body weight (150 mg ml^?1), was infused for 4–14 min and blood samples taken at 1‐, 2‐, 3‐ and 4‐h (n = 24) or 2‐, 3‐, 3·5‐ and 4‐h after infusion (n = 17). Mannitol in serum was measured by an enzymatic method. Plasma clearance for mannitol and its apparent volume of distribution (Vd) were calculated according to Brøchner‐Mortensen. Mean plasma clearance (±SD) for ⁵¹Cr‐EDTA was 59·7 ± 18·8 ml min^?1. The mean plasma clearance for mannitol ranged between 57·0 ± 20·1 and 61·1 ± 16·7 ml min^?1 and Vd was 21·3 ± 6·2% per kg b.w. The between‐method bias ranged between ?0·23 and 2·73 ml min^?1, the percentage error between 26·7 and 39·5% and the limits of agreement between ?14·3/17·2 and ?25·3/19·9 ml min^?1. The best agreement was seen when three‐ or four‐sample measurements of plasma mannitol were obtained and when sampling started 60 min after injection. Furthermore, accuracy of plasma clearance determinations was 88–96% (P30) and 41–63% (P10) and was highest when three‐ or four‐sample measurements of plasma mannitol were obtained, including the first hour after the bolus dose. We conclude that there is a good agreement between plasma clearances of mannitol and ⁵¹Cr‐EDTA for the assessment of GFR.     

Is arterial stiffening in Alström syndrome linked to the development of cardiomyopathy?

Background Alström syndrome (AS) is a rare autosomal recessive condition characterized by retinal degeneration, childhood obesity, and severe insulin resistance. Dilated cardiomyopathy of unknown aetiology is a well‐recognized and potentially lethal complication. The aim of this study was to investigate the relationship between vascular function, hyperinsulinaemia and cardiac performance in AS. Materials and methods Fifteen subjects with AS (mean age 21 years, range 10–35) were studied and compared with age‐, sex‐, and blood pressure‐matched healthy controls. Large artery stiffness and wave reflections were assessed in both groups by measuring aortic and brachial pulse wave velocity (PWV) (carotid‐femoral and carotid‐radial) and augmentation index (AIX) (Sphygmocor). In AS subjects, left ventricular function was assessed by echocardiography and metabolic parameters including fasting insulin, glucose, lipids and brain natriuretic peptide were also measured. Results Comparing AS subjects vs. controls (mean ± SD), AIX was elevated in AS subjects (18 ± 9% vs. 3 ± 11%, P < 0·0001). No significant changes in brachial PWV (8·1 ± 1·3 m s⁻¹ vs. 7·3 ± 1·1 m s⁻¹, P = 0·14) or aortic PWV (6·5 ± 1·1 m s⁻¹ vs. 6·0 ± 1·0 m s⁻¹, P = 0·26) were observed. AS subjects were hyperinsulinaemic and had disturbances in lipid profiles relative to controls. No correlations were observed between vascular, metabolic and echocardiographic parameters. Conclusions In AS there are alterations in the shape of the central arterial pressure waveform associated with augmented aortic systolic pressure and indicative of increased wave reflection. Unfavourable central arterial haemodynamics in AS may contribute to the development of cardiomyopathy but other aetiological factors are probably involved.