Lung aeration during sleep in patients with obstructive sleep apnoea

Background: Previous studies have indicated that patients with obstructive sleep apnoea (OSA) have altered ventilation and lung volumes awake and the results suggest that this may be a determinant of severity of desaturations during sleep. However, little is known about regional lung aeration during sleep in patients with OSA. Methods: Twelve patients with OSA were included in the study. Computed tomography was used to study regional lung aeration during wakefulness and sleep. Lung aeration was calculated in ml gas/g lung tissue in four different regions of interest (ROI_1–4), along the border of the lung from ventral to dorsal. Results: Lung aeration in the dorsal (dependent) lung region (ROI₄) was lower during sleep compared to wakefulness 0·78 ± 0·19 versus 0·88 ± 0·19 (mean ± SD) ml gas/g lung tissue (P = 0·005). Associations were found between awake expiratory reserve volume and change in lung aeration from wakefulness to sleep in ROI₄ (r = ?0·69; P = 0·012). In addition, the change in lung aeration in the dorsal region correlated to sleep time (r = 0·69; P = 0·014) but not to time in supine position. The difference in lung aeration between inspiration and expiration (i.e. ventilation), was larger in the ventral lung region when expressed as ml gas per g lung tissue. In two patients it was noted that, during on‐going obstructive apnoea, lung aeration tended to be increased rather than decreased. Conclusions: Aeration in the dorsal lung region is reduced during sleep in patients with OSA. The decrease is related to lung volume awake and to sleep time.     

Reduced preload elicits increased LV twist in healthy humans: an echocardiographic speckle-tracking study during lower body negative pressure

Background: In normal left ventricles (LV), counterclockwise rotation (CCR) and net twist angle (NTA) have shown important roles during ejection. We investigated the effect of reduced preload by lower body negative pressure (LBNP) on CCR and NTA. Methods and Results: Twelve healthy men were examined at rest, LBNP ?20 and ?40 mmHg. By two‐dimensional speckle‐tracking imaging, we measured rotation at four short‐axis levels: basal, papillary, sub‐papillary and apical. LV NTA was calculated as apex‐to‐base difference in rotation. Additionally, regional end‐diastolic (EDA) and end‐systolic area (ESA) were measured and regional area fraction (RAF) calculated [(EDA‐ESA)/EDA] × 100). From rest to LBNP ?40 mmHg, rotation at basal and papillary levels was unchanged. At sub‐papillary level, rotation increased from 3·2 ± 3·6 to 5·8 ± 4·7° (P<0·05), while apical rotation increased from 9·3 ± 3·4 to 12·8 ± 4·7° (P<0·05). Correspondingly, LV NTA increased for each load reduction by 1·6 ± 1·8° (P<0·05) and 4·2 ± 2·3° (P<0·05). RAF increased at sub‐papillary and apical levels from 57·6 ± 3·7 to 64·7 ± 8·8% and from 63·4 ± 8·8 to 74·8 ± 10·1%, respectively (P<0·05). From rest to LBNP ?40 mmHg, changes in rotation and RAF correlated significantly at sub‐papillary and apical levels (r = 0·94, P<0·01, and r = 0·63, P<0·05, respectively). Conclusions: Preload reduction in normal LV elicits increased systolic CCR and regional area fraction at sub‐papillary and apical levels as well as net twist angle. These findings might be of physiological importance to minimize reduction in stroke volume and maintain arterial blood pressure.     

Calculation algorithms alter the breath‐by‐breath gas exchange values when abrupt changes in ventilation occur

The automatic metabolic units calculate breath‐by‐breath gas exchange from the expiratory data only, applying an algorithm (‘expiration‐only’ algorithm) that neglects the changes in the lung gas stores. These last are theoretically taken into account by a recently proposed algorithm, based on an alternative view of the respiratory cycle (‘alternative respiratory cycle’ algorithm). The performance of the two algorithms was investigated where changes in the lung gas stores were induced by abrupt increases in ventilation above the physiological demand. Oxygen, carbon dioxide fractions and ventilatory flow were recorded at the mouth in 15 healthy subjects during quiet breathing and during 20‐s hyperventilation manoeuvres performed at 5‐min intervals in resting conditions. Oxygen uptakes and carbon dioxide exhalations were calculated throughout the acquisition periods by the two algorithms. Average ventilation amounted to 6·1 ± 1·4 l min^?1 during quiet breathing and increased to 41·8 ± 27·2 l min^?1 during the manoeuvres (P<0·01). During quiet breathing, the two algorithms provided overlapping gas exchange data and noise. Conversely, during hyperventilation, the ‘alternative respiratory cycle’ algorithm provided significantly lower gas exchange data as compared to the values yielded by the ‘expiration‐only’ algorithm. For the first breath of hyperventilation, the average values provided by the two algorithms amounted to 0·37 ± 0·34 l min^?1 versus 0·96 ± 0·73 l min^?1 for O₂ uptake and 0·45 ± 0·36 l min^?1 versus 0·80 ± 0·58 l min^?1 for exhaled CO₂ (P<0·001 for both). When abrupt increases in ventilation occurred, such as those arising from a deep breath, the ‘alternative respiratory cycle’ algorithm was able to halve the artefactual gas exchange values as compared to the ‘expiration‐only’ approach.     

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.     

Endothelin‐1: increased plasma clearance,pulmonary affinity and renal vasoconstriction in young smokers

Pulmonary and renal haemodynamics and elimination of endothelin‐1 (ET‐1) were studied in six young smokers in response to 20 min intravenous infusion of ET‐1 (4 pmol kg^–1 min^–1) after smoking. At 20 min of ET‐1 infusion fractional ET‐1 extractions in the lungs and kidneys were 60 ± 2 and 60 ± 7%, respectively. Cardiac output and renal blood flow (RBF) fell by 18 ± 4% (P<0·05) and 34 ± 5% (P<0·01). Mean systemic arterial pressure increased (P<0·05) whereas pulmonary pressures were unchanged. Compared with previously published data in non‐smokers ( 38 , 39 ) basal arterial ET‐1 and ET‐1‐values during ET‐1 infusion were lower with a more rapid return to basal value. Smokers had higher pulmonary extraction of ET‐1 at the same pulmonary arterial concentration (P<0·05). RBF reduction was more pronounced (P<0·05). Systemic vascular resistance increased while pulmonary vascular resistance did not increase as in non‐smokers. Increased plasma clearance and more efficient pulmonary elimination of ET‐1 lowers the arterial level in young smokers. In addition ET‐1 evokes more pronounced renal vasoconstriction in these individuals.     

Maintained cerebral metabolic ratio during exercise in patients with β‐adrenergic blockade

Background: Decreased cerebral metabolic ratio (CMR) [molar uptake of O₂ versus molar uptake of (glucose + ½ lactate)] during exercise is attenuated by intravenous administration of the non‐selective β‐adrenergic receptor antagonist propranolol. We evaluated to what extent cirrhotic patients in oral treatment with propranolol are able to mobilize brain non‐oxidative carbohydrate metabolism. Methods: Incremental cycle ergometry to exhaustion (86 ± 4·2 W; mean ± SD) was performed in eight cirrhotic patients instrumented with a catheter in the brachial artery and one retrograde in the right internal jugular vein. Healthy subjects form the control group. Results: In β‐blocked cirrhotic patients arterial lactate increased from 1·5 ± 0·3 to 5·1 ± 0·8 mM (P<0·05) and the arterial–jugular venous difference (a–v diff) from ?0·01 ± 0·03 to 0·30 ± 0·05 mM (P<0·05) at rest and during exercise, respectively. During exercise the glucose a–v diff of 0·46 ± 0·06 mM remained at a level similar to rest (0·54 ± 0·03 mM) and at exhaustion the CMR was not significantly changed (5·8 ± 1·1 versus 6·0 ± 0·6). In controls, CMR decreased from 5·6 ± 0·9 at rest to 3·4 ± 0·7 (P<0·05) during maximal exercise and at a lactate level comparable to that achieved by the patients it was 3·8 ± 0·4. Conclusion: During exhaustive exercise in cirrhotic patients the CMR is maintained and a significant cerebral uptake of lactate is demonstrated. The data suggest that oral treatment with a non‐selective β‐adrenergic receptor antagonist attenuates cerebral non‐oxidative metabolism.     

Cardiac power output and its response to exercise in athletes and non‐athletes

Cardiac power output (CPO) is an integrative measure of overall cardiac function as it accounts for both, flow‐ and pressure‐generating capacities of the heart. The purpose of the present study was twofold: (i) to assess cardiac power output and its response to exercise in athletes and non‐athletes and (ii) to determine the relationship between cardiac power output and reserve and selected measures of cardiac function and structure. Twenty male athletes and 32 age‐ and gender‐matched healthy sedentary controls participated in this study. CPO was calculated as the product of cardiac output and mean arterial pressure, expressed in watts. Measures of hemodynamic status, cardiac structure and pumping capability were assessed by echocardiography. CPO was assessed at rest and after peak bicycle exercise. At rest, the two groups had similar values of cardiac power output (1·08 ± 0·2 W versus 1·1 ± 0·24 W, P>0·05), but the athletes demonstrated lower systolic blood pressure (109·5 ± 6·2 mmHg versus 117·2 ± 8·2 mmHg, P<0·05) and thicker posterior wall of the left ventricle (9·8 ± 1 mm versus 9 ± 1·1 mm, P<0·05). Peak CPO was higher in athletes (5·87 ± 0·75 W versus 5·4 ± 0·69 W, P<0·05) as was cardiac reserve (4·92 ± 0·66 W versus 4·26 ± 0·61 W, P<0·05), respectively. Peak exercise CPO and reserve were only moderately correlated with end‐diastolic volume (r = 0·54; r = 0·46, P<0·05) and end‐diastolic left ventricular internal diameter (r = 0·48; r = 0·42, P<0·05), respectively. Athletes demonstrated greater maximal cardiac pumping capability and reserve than non‐athletes. The study provides new evidence that resting measures of cardiac structure and function need to be considered with caution in interpretation of maximal cardiac performance.     

Temporal age‐related changes in spectral,fractal and complexity characteristics of heart rate variability

Cross‐sectional studies have suggested that heart rate (HR) variability, analysed using traditional time and frequency domain methods, is related to ageing, but no longitudinal studies have estimated the age dependence of HR fluctuation. This study evaluated temporal age‐related changes in 12‐h measures of HR variability among 109 patients with coronary artery disease (CAD), who underwent repeat Holter recordings at 32‐month intervals. Time and frequency domain measures, along with fractal and complexity measures of HR variability, were determined at the baseline and after 32 months. Changes in HR dynamics were compared with various laboratory variables, exercise data and angiographic progression of CAD. Traditional time and frequency domain measures of HR variability did not change significantly during the follow‐up, but the power‐law scaling slope decreased from ?1·29 ± 0·20 to ?1·36 ± 0·23 (P<0·01) and the short‐term fractal exponent (α₁) of HR dynamics from 1·29 ± 0·14–1·22 ± 0·18 (P<0·001). The approximate entropy value also decreased from 1·00 ± 0·19 to 0·95 ± 0·18 (P<0·05). The changes in HR behaviour were not related to demographic data, laboratory values or angiographic progression of CAD. Only a weak correlation was observed between the change in the power‐law slope and the baseline glucose value (P<0·05). This longitudinal study shows that the fractal characteristics of HR dynamics and the complexity properties of R‐R intervals undergo rapid changes along with ageing, and that fractal and complexity analysis techniques are more sensitive than traditional analysis methods in documenting temporal age‐related changes in HR behaviour.     

Influence of arterial wave reflection on carotid blood pressure and intima‐media thickness in older endurance trained men and women with pre‐hypertension

Increased carotid intima‐media thickness (IMT) with aging is a significant predictor of mortality. Older endurance trained (ET) individuals have lower carotid artery stiffness but similar carotid IMT when compared to sedentary (SED) age‐matched peers. The purpose of this study was to examine the contribution of arterial wave reflections to carotid hemodynamics and IMT in older ET and SED with pre‐hypertension. Subjects consisted of endurance‐trained master athletes and age‐matched sedentary controls (mean age 67 years). Carotid artery Beta‐stiffness index and IMT was assessed with ultrasonography. Carotid pressure and augmented pressure from wave reflections (obtained from pulse contour analysis) was measured with applanation tonometry. Carotid systolic blood pressure (SBP) and IMT were not different between groups (P>0·05). Carotid stiffness was significantly lower in ET versus SED (7·3 ± 0·8 versus 9·9 ± 0·6, P<0·05). Augmented pressure was significantly greater in ET versus SED (17·7 ± 1·6 versus 13·3 ± 1·5 mmHg, P<0·05). When adjusting for differences in resting heart rate, there were no group differences in augmented pressure. In conclusion, older ET persons with pre‐hypertension have reduced carotid artery stiffness, but similar carotid SBP and carotid IMT when compared to SED. The lack of change in carotid SBP and IMT in older ET may be related to the inability of chronic exercise training to reduce bradycardia‐related augmented pressure from wave reflections with aging.     

Comparison of SSRIs and SNRIs in major depressive disorder: a meta‐analysis of head‐to‐head randomized clinical trials

Context: Controversy exists whether serotonin–norepinephrine reuptake inhibitors (SNRIs) have improved efficacy compared with selective serotonin reuptake inhibitors (SSRIs). Objective: To compare clinical outcomes of adults treated with SSRIs or SNRIs for major depressive disorder (MDD) under ideal clinical condition, research design, and outcome measure. Data sources: Electronic databases searched were Medline, Embase and Cochrane Library from inception to July 2007. Study selection: Included studies were those head‐to‐head randomized trials comparing remission (HAMD‐17 ≤7–8, MADRS ≤10–12) after 8–12 weeks of therapeutic doses of SSRIs or SNRIs in patients diagnosed with MDD were targeted for analysis. Reviews, letters, commentaries, economic studies, etc. were excluded. Studies were reviewed by two independent researchers. Where disagreements occurred in study selection, a consensus approach was used. Data extraction and analysis: Targeted outcome data included number of patients achieving remission, withdrawing from therapy due to lack of efficacy (LoE) and/or adverse drug reactions (ADRs), and total patients in trial. A random effects model combined intent‐to‐treat (ITT) and per‐protocol (PP) odds ratio (OR), and remission and dropout rates. Chi‐square assessed heterogeneity. Quality assessment was done using Downs‐Black checklist. Results: Thirty‐three studies were identified; 18 were rejected (patients had co‐morbidities in 7, outcomes differed in 5, different follow‐up in 3, and three reviews). Fifteen head‐to‐head trials of 3094 patients, average age was 41·9 ± 11·9 years (for SNRIs) and 41·6 ± 12·1 years (for SSRIs), P = 0·941. All analyses displayed non‐heterogeneity (P > 0·05). The OR (under ITT) was 1·27 (1·06–1·52 95% CI) favoring SNRIs. Meta‐analytic remission rates were 48·5 ± 3·2% and 41·9 ± 4·2% for SNRIs and SSRIs, respectively. The meta‐analytic difference in remission rates between drugs was 5·7% (P = 0·007). Dropout rates due to ADRs were higher with SNRIs than SSRIs (3·2% difference, P < 0·001). Dropout rates due to LoE were non‐significant between studied groups (P > 0·05). Conclusions: Serotonin and norepinephrine reuptake inhibitors showed statistical but not clinical significance when compared with SSRIs in treating MDD.     

Effect of positive end‐expiratory pressure on acoustic wave propagation in experimental porcine lung injury

To evaluate the effect of positive end‐expiratory pressure (PEEP) on sound propagation through injured lungs, we injected a multifrequency broad‐band sound signal into the airway of eight anesthetized, intubated and mechanically ventilated pigs, while recording transmitted sound at three locations bilaterally on the chest wall. Oleic acid injections effected a severe pulmonary oedema predominately in the dependent lung regions, with an average increase in venous admixture from 19 ± 15 to 59 ± 14% (P<0·001), and a reduction in dynamic respiratory system compliance from 34 ± 7 to 14 ± 4 ml cmH₂O^?1 (P<0·001). A concomitant decrease in sound transit time was seen in the dependent lung regions (P<0·05); no statistically significant change occurred in the lateral or non‐dependent areas. The application of PEEP resulted in a decrease in venous admixture, increase in respiratory system compliance and return of the sound transit time to pre‐injury levels in the dependent lung regions. Our results indicate that sound transmission velocity increases in lung tissue affected by permeability‐type pulmonary oedema in a manner reversible during alveolar recruitment with PEEP.     

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.     

Morpho‐functional response of the elbow extensor muscles to twelve‐week self‐perceived maximal resistance training

The aim of this study was to determine morphological and functional changes of the elbow extensor muscles in response to a 12‐week self‐perceived maximal resistance training (MRT). Twenty‐one healthy sedentary young men were engaged in elbow extensor training using isoacceleration dynamometry for 12 weeks with a frequency of five sessions per week (five sets of ten maximal voluntarily contractions, 1‐min rest period between each set). Prior to, at 6 weeks and after the training, a series of cross‐sectional magnetic resonance images of the upper arm were obtained and muscle volumes were calculated. Maximal and endurance strength increased (P<0·01) by 15% and 45% at 6 weeks, and by 29% and 70% after 12 weeks compared with baseline values, while fatigue rate of the elbow extensors decreased by 67%. The volume of triceps brachii increased in both arms (P<0·01) by 4% at 6 weeks, and by 8% after 12 weeks compared with baseline values (right arm – from 487·4 ± 72·8 cm³ to 505·8 ± 72·3 cm³ after 6 weeks and 525·3 ± 73·7 cm³ after 12 weeks; left arm – from 475·3 ± 79·1 cm³ to 493·2 ± 72·7 cm³ after 6 weeks and 511·3 ± 77·0 cm³ after 12 weeks). A high correlation was found between maximal muscle strength and muscle volume prior (r² = 0·62) and after (r² = 0·69) the training (P≤0·05). A self‐perceived MRT resulted in an increase in maximal and endurance strength. Morphological adaptation changes of triceps brachii as a result of 12‐week specific strength training can explain only up to 26% of strength gain.     

Functional near‐infrared spectroscopy to probe sensorimotor region activation during electrical stimulation‐evoked movement

This study used non‐invasive functional near‐infrared spectroscopy (fNIRS) neuroimaging to monitor bilateral sensorimotor region activation during unilateral voluntary (VOL) and neuromuscular electrical stimulation (NMES)‐evoked movements. Methods. In eight healthy male volunteers, fNIRS was used to measure relative changes in oxyhaemoglobin (O₂Hb) and deoxyhaemoglobin (HHb) concentrations from a cortical sensorimotor region of interest in the left (LH) and right (RH) hemispheres during NMES‐evoked and VOL wrist extension movements of the right arm. Results. NMES‐evoked movements induced significantly greater activation (increase in O₂Hb and concomitant decrease in HHb) in the contralateral LH than in the ipsilateral RH (O₂Hb: 0·44 ± 0·16 μM and 0·25 ± 0·22 μM, P = 0·017; HHb: ?0·19 ± 0·10 μM and ?0·12 ± 0·09 μM, P = 0·036, respectively) as did VOL movements (0·51 ± 0·24 μΜ and 0·34 ± 0·21 μM, P = 0·031; HHb: ?0·18 ± 0·07 μΜ and ?0·12 ± 0·04 μΜ, P = 0·05, respectively). There was no significant difference between conditions for O₂Hb (P = 0·144) and HHb (P = 0·958). Conclusion. fNIRS neuroimaging enables quantification of bilateral sensorimotor regional activation profiles during voluntary and NMES‐evoked wrist extension movements.     

Effect of 2 days of intensive resistance training on appetite‐related hormone and anabolic hormone responses

This study was designed to determine endocrine responses during 2 days of strenuous resistance training. Ten healthy men performed resistance training twice a day for two successive days to induce acute fatigue (excessive physical stress). The resistance training consisted of four exercises for the lower body in the morning and seven exercises for the upper body in the afternoon. Maximal isometric and isokinetic strengths were measured from day 1 (before the training period) to day 3 (after the training period). Fasting blood samples were taken on days 1–3. Maximal isometric and isokinetic strengths significantly decreased with two successive days of training (P<0·05), with significant increases in serum creatine phosphokinase and myoglobin concentrations (P<0·05). Significant reductions in the fasting concentrations of serum insulin‐like growth factor‐1, free testosterone, insulin and high‐molecular‐weight adiponectin were observed on day 3 (P<0·05), whereas there were no changes in the serum cortisol concentration or the free testosterone/cortisol ratio. Plasma active ghrelin and serum leptin concentrations decreased by ?20·7 ± 2·8% and ?29·6 ± 4·1%, respectively (P<0·05). Two days strenuous resistance training significantly affects the profiles of anabolic hormone and endocrine regulators of appetite and energy balance, such as ghrelin and leptin. The present findings suggest that decreased ghrelin and leptin concentrations might reflect excessive physical stress and may be early signs of accumulated fatigue.     

A new vessel segmentation algorithm for robust blood flow quantification from two‐dimensional phase‐contrast magnetic resonance images

Blood flow measurements in the ascending aorta and pulmonary artery from phase‐contrast magnetic resonance images require accurate time‐resolved vessel segmentation over the cardiac cycle. Current semi‐automatic segmentation methods often involve time‐consuming manual correction, relying on user experience for accurate results. The purpose of this study was to develop a semi‐automatic vessel segmentation algorithm with shape constraints based on manual vessel delineations for robust segmentation of the ascending aorta and pulmonary artery, to evaluate the proposed method in healthy volunteers and patients with heart failure and congenital heart disease, to validate the method in a pulsatile flow phantom experiment, and to make the method freely available for research purposes. Algorithm shape constraints were extracted from manual reference delineations of the ascending aorta (n = 20) and pulmonary artery (n = 20) and were included in a semi‐automatic segmentation method only requiring manual delineation in one image. Bias and variability (bias ± SD) for flow volume of the proposed algorithm versus manual reference delineations were 0·0 ± 1·9 ml in the ascending aorta (n = 151; seven healthy volunteers; 144 heart failure patients) and ?1·7 ± 2·9 ml in the pulmonary artery (n = 40; 25 healthy volunteers; 15 patients with atrial septal defect). Interobserver bias and variability were lower (P = 0·008) for the proposed semi‐automatic method (?0·1 ± 0·9 ml) compared to manual reference delineations (1·5 ± 5·1 ml). Phantom validation showed good agreement between the proposed method and timer‐and‐beaker flow volumes (0·4 ± 2·7 ml). In conclusion, the proposed semi‐automatic vessel segmentation algorithm can be used for efficient analysis of flow and shunt volumes in the aorta and pulmonary artery.     

Comparison of bioimpedance and radioisotope methods in the estimation of extracellular water volume before and after coronary artery bypass grafting operation

To estimate extracellular water volume (ECW) changes in connection with coronary artery bypass grafting operation, simultaneous ECW estimations by ⁵¹Cr‐EDTA dilution and whole‐body bioimpedance techniques were performed in 15 patients. The assessments of ECW were compared with patients’ weighing results. Whole‐body bioimpedance‐derived ECW correlated significantly with ⁵¹Cr‐EDTA dilution‐based ECW in the pre‐operative period (r=0·74; P<0·005); the bias was 0·2 ± 1·1 l (±SD). In the post‐operative period, the agreement between these methods was poor, the bias being 0·5 ± 2·5 l, and no significant correlation between the methods was found (r=0·38; P>0·05). Whole‐body bioimpedance‐derived ECW changes correlated significantly with weight changes of the patient induced by the operation (r=0·52; P<0·05). ⁵¹Cr‐EDTA dilution‐based ECW changes correlated neither with weight changes (r=0·33; P>0·05) nor with bioimpedance‐derived ECW changes (r=0·03; P>0·05). Alterations in radioisotope tracer distribution and loss of it due to blood leakage in the post‐operative period were presumed to explain the discrepancy between dilution technique and weighing results. The results suggest that bioimpedance is a useful non‐invasive method for assessment of extracellular volume changes induced by coronary artery bypass grafting operations. ⁵¹Cr‐EDTA dilution‐based ECW determination is not suitable in related conditions.     

Postprandial impairment of resistance vessel function in insulin treated patients with diabetes mellitus type‐2

Reduced postischaemic reactive hyperaemia, is considered a marker of impaired resistance vessel function. Acute postprandial hyperlipidaemia has been shown to induce vascular dysfunction. In the present study, the impact of postprandial hyperglycaemia on resistance vessel reactivity was investigated in insulin treated type‐2 diabetic patients. The study was performed in 16 insulin treated type‐2 diabetics (eight male/eight female, age 47 ± 3 years, HbA1c 7·2 ± 0·2) and 16 controls. Reactive hyperaemia was measured in the forearm by venous occlusion plethysmography after 5 min of ischaemia in the fasting state and 90 min after a test meal. In diabetics, blood glucose increased from 8·7 ± 1·1 to 15·3 ± 1·0 mmol l^?1 (P<0·001) postprandially. This resulted in (i) a significant increase of resting blood flow (3·4 ± 0·3 to 4·8 ± 0·4 ml min^?1 100 ml^?1, P<0·01) and (ii) in a reduced peak reactive hyperaemia (52·3 ± 7·4 to 36·8 ± 4·3 ml min^?1 100 ml^?1, P<0·005). In controls, a similar effect of the meal on resting flow was observed but reactive hyperaemia was unaltered. In the absence of a test meal, basal flow as well as peak reactive hyperaemia remained unchanged in diabetic as well as in non‐diabetic subjects. Our data provide evidence that in the postprandial state resistance vessel reactivity becomes reduced in insulin treated type‐2 diabetic patients.     

Leg uptake of calcitonin gene‐related peptide during exercise in spinal cord injured humans

Exercise‐induced increases in cardiac output (CO) and oxygen uptake (VO₂) are tightly coupled, as also in absence of central motor activity and neural feedback from skeletal muscle. Neuromodulators of vascular tone and cardiac function – such as calcitonin gene related peptide (CGRP) – may be of importance. Spinal cord injured individuals (six tetraplegic and four paraplegic) performed electrically induced cycling (FES) with their paralyzed lower limbs for 29 ± 2 min to fatigue. Voluntary cycling performed both at VO₂ similar to FES and at maximal exercise in six healthy subjects served as control. In healthy subjects, CGRP in plasma increased only during maximal exercise (33·8 ± 3·1 pmol l^?1 (rest) to 39·5 ± 4·3 (14%, P<0·05)) with a mean extraction over the working leg of 10% (P<0·05). Spinal cord injured individuals had more pronounced increase in plasma CGRP (33·2 ± 3·8 to 46·9 ± 3·6 pmol l^?1, P<0·05), and paraplegic and tetraplegic individuals increased in average by 23% and 52%, respectively, with a 10% leg extraction in both groups (P<0·05). The exercise induced increase in leg blood flow was 10–12 fold in both spinal cord injured and controls at similar VO₂ (P<0·05), whereas CO increased more in the controls than in spinal man. Heart rate (HR) increased more in paraplegic subjects (67 ± 7 to 132 ± 15 bpm) compared with controls and tetraplegics (P<0·05). Mean arterial pressure (MAP) was unchanged during submaximal exercise and increased during maximal exercise in healthy subjects, but decreased during the last 15 min of exercise in the tetraplegics. It is concluded that plasma CGRP increases during exercise, and that it is taken up by contracting skeletal muscle. The study did not allow for a demonstration of the origin of the CGRP, but its release does not require activation of motor centres. Finally, the more marked increase in plasma CGRP and the decrease in blood pressure during exercise in tetraplegic humans may indicate a role of CGRP in regulation of vascular tone during exercise.