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Aims: The study's aim is to compare current and new equations for estimating glomerular filtration rate (GFR) based on creatinine, cystatin C, β-trace protein (BTP) and β2 microglobulin (B2M) among patients undergoing major amputation. Methods: This is a secondary analysis of data from a prospective cohort study investigating patients undergoing nontraumatic lower extremity amputation. Estimated GFR (eGFR) was calculated using equations based on creatinine (eGFRcre[2009] and eGFRcre[2021]), cystatin C (eGFRcys), the combination of creatinine and cystatin C (eGFRcomb[2012] and eGFRcomb[2021]) or a panel of all 4 filtration markers (eGFRpanel). Primary outcome was changed in eGFR across amputation according to each equation. Two case studies of prior amputation with GFR measured by 99mTc-DTPA clearance are described to illustrate the relative accuracies of each eGFR equation. Results: Analysis of the primary outcome included 29 patients (median age 75 years, 31% female). Amputation was associated with a significant decrease in creatinine concentration (−0.09 mg/dL, P = 0.004), corresponding to a significant increase in eGFRcre[2009] (+6.1 mL/min, P = 0.006) and eGFRcre[2021] (+6.3 mL/min, P = 0.006). Change across amputation was not significant for cystatin C, BTP, B2M or equations incorporating these markers (all P > 0.05). In both case studies, eGFRcre[2021] yielded the largest positive bias, eGFRcys yielded the largest negative bias and eGFRcomb[2012] and eGFRcomb[2021] yielded the smallest absolute bias. Conclusion: Creatinine-based estimates were substantially higher than cystatin C-based estimates before amputation and significantly increased across amputation. Estimates combining creatinine and cystatin were stable across amputation, while the addition of BTP and B2M is unlikely to be clinically relevant.

Background Internationally, older patients (≥65 years) account for more than 40% of acute admissions. Older patients admitted to the emergency department (ED) are frequently malnourished and exposed to inappropriate medication prescribing, due in part to the inaccuracy of creatinine-based equations for estimated glomerular filtration rate (eGFR). The overall aims of this trial are to investigate: (1) the efficacy of a medication review (MED intervention) independent of nutritional status, (2) the accuracy of eGFR equations based on various biomarkers compared to measured GFR (mGFR) based on 99mTechnetium–diethylenetriaminepentaacetic acid plasma clearance, and (3) the efficacy of an individualized multimodal and transitional nutritional intervention (MULTI-NUT-MED intervention) in older patients with or at risk of malnutrition in the ED. Methods The trial is a single-center block randomized, controlled, observer-blinded, superiority and explorative trial with two parallel groups. The population consists of 200 older patients admitted to the ED: 70 patients without malnutrition or risk of malnutrition and 130 patients with or at risk of malnutrition defined as a Mini Nutritional Assessment-Short Form score ≤11. All patients without the risk of malnutrition receive the MED intervention, which consists of a medication review by a pharmacist and geriatrician in the ED. Patients with or at risk of malnutrition receive the MULTI-NUT-MED intervention, which consists of the MED intervention in addition to, dietary counseling and individualized interventions based on the results of screening tests for dysphagia, problems with activities of daily living, low muscle strength in the lower extremities, depression, and problems with oral health. Baseline data are collected upon study inclusion, and follow-up data are collected at 8 and 16 weeks after discharge. The primary outcomes are (1) change in medication appropriateness index (MAI) score from baseline to 8 weeks after discharge, (2) accuracy of different eGFR equations compared to mGFR, and (3) change in health-related quality of life (measured with EuroQol-5D-5L) from baseline to 16 weeks after discharge. Discussion The trial will provide new information on strategies to optimize the treatment of malnutrition and inappropriate medication prescribing among older patients admitted to the ED. Trail registration ClinicalTrials.gov NTC03741283. Retrospectively registered on 14 November 2018.

SummaryBackground Bile acid diarrhoea is underdiagnosed and better diagnostic tests are needed. Fasting serum fibroblast growth factor-19 (FGF19) has insufficient diagnostic value, but this may be improved by stimulation. Aim To explore if an impaired FGF19 response identifies primary bile acid diarrhoea. Methods Eight patients with primary bile acid diarrhoea and eight healthy volunteers ingested (i) a meal plus 1250 mg chenodeoxycholic acid (CDCA), (ii) 1250 mg CDCA or (iii) the meal. Blood was sampled at fasting and repeatedly after stimulation. We analysed FGF19 by enzyme-linked immunosorbent assay and bile acids including 7α-hydroxy-4-cholesten-3-one by liquid chromatography-tandem mass spectrometry. Results Stimulation with the meal plus CDCA increased median FGF19 in healthy volunteers from fasting 62 pg/mL [interquartile range (IQR): 41–138] to 99 pg/mL (IQR: 67–147; P = 0.012) after 90 min and peaked after 150 min at 313 pg/mL (IQR: 54–512). This response was impaired in primary bile acid diarrhoea patients [fasting 56 pg/mL (IQR: 42–79); 90 min: 48 pg/mL [IQR: 37–63); 150 min: 57 pg/mL (48–198)]. Receiver operating characteristics (ROCAUC) for fasting FGF19 was 0.55 (P = 0.75) and at 90 min 0.84 (P = 0.02). The difference in FGF19 from fasting to 90 min after the meal plus CDCA separated the groups (ROCAUC 1.0; P = 0.001). 7α-hydroxy-4-cholesten-3-one was elevated in primary bile acid diarrhoea (P = 0.038) and not significantly affected by stimulation. Conclusions The FGF19 response following chenodeoxycholic acid plus meal is impaired in primary bile acid diarrhoea. This may provide a biochemical diagnostic test.

Background: Generally, eating salty food items increases thirst. Thirst is also stimulated by the experimental infusion of hypertonic saline. But, in steady state, does the kidney need a higher amount of water to excrete sodium on a high than on a low sodium intake? This issue is still controversial. The purpose of this review is to provide examples of how the kidney handles water in relation to salt intake/output. It is based on re-analysis of previously published studies in which salt intake was adjusted to several different levels in the same subjects, and in databases of epidemiologic studies in populations on an ad libitum diet. Summary and Key Messages: These re-analyses allow us to draw the following conclusions: (1) In a steady state situation, the urine volume (and thus the fluid intake) remains unchanged over a large range of sodium intakes. The adaptation to a higher sodium excretion rests only on changes in urinary sodium concentration. However, above a certain limit, this concentration cannot increase further and the urine volume may then increase. (2) In population studies, it is not legitimate to assume that sodium is responsible for changes in urine volume, since people who eat more sodium also eat more of other nutrients leading to an increase in the excretion of potassium, urea and other solutes, besides sodium. (3) After an abrupt increase in sodium intake, fluid intake is increased in the first few days, but urine volume does not change. The extra fluid drunk is responsible for an increase in body weight.

A deficiency in the ileal hormone fibroblast growth factor 19 (FGF19) has been described in patients with bile acid diarrhoea (BAD), but fasting FGF19 levels have insufficient diagnostic power. We assess whether single postprandial sampling of FGF19 has greater discriminative value than fasting FGF19 for detection of BAD and we evaluate the reproducibility of fasting FGF19.Twenty-six patients consecutively referred to Se homocholic acid retention test (SeHCAT) were included. Serum FGF19 was measured after an overnight fast and again 1 h postprandially and again in the fasting state 1 week later.Nine of 26 patients had SeHCAT less than 10% and fasting FGF19 was lower [median 62 pg/ml, interquartile range (IQR): 47-67] than in the 17 diarrhoea controls with SeHCAT at least 10% (median 103 pg/ml, IQR: 77-135, P=0.006). Postprandial FGF19 in BAD patients (61 pg/ml, IQR: 48-69) was similar to fasting values (P=0.59) and increased insignificantly in diarrhoea controls (137 pg/ml, IQR: 88-182; P=0.25). The difference in postprandial FGF19 between patients with BAD and diarrhoea controls was highly significant (P0.001).The difference in serum FGF19 between groups of patients with BAD and diarrhoea controls is amplified postprandially. Within each group, the difference between fasting and postprandial FGF19 was not statistically significant. Further investigations are warranted on stimulated FGF19 response to elucidate its role in BAD.

It is known that arterial pressure correlates positively with body height in males, and it has been suggested that this is due to the increasing vertical hydrostatic gradient from the heart to the carotid baroreceptors. Therefore, we tested the hypothesis that a higher gravito-inertial stress induced by the use of a human centrifuge would increase mean arterial pressure (MAP) more in tall than in short males in the seated position. In short (162–171 cm; n = 8) and tall (194–203 cm; n = 10) healthy males (18–41 yr), brachial arterial pressure, heart rate (HR), and cardiac output were measured during +2G centrifugation, while they were seated upright with the legs kept horizontal (+2Gz). In a separate experiment, the same measurements were done with the subjects supine (+2Gx). During +2Gz MAP increased in the short (22 ± 2 mmHg, P < 0.0001) and tall (23 ± 2 mmHg, P < 0.0001) males, with no significant difference between the groups. HR increased more ( P < 0.05) in the tall than in the short group (14 ± 2 vs. 7 ± 2 bpm). Stroke volume (SV) decreased in the short group (26 ± 4 ml, P = 0.001) and more so in the tall group (39 ± 5 ml, P < 0.0001; short vs. tall, P = 0.047). During +2Gx, systolic arterial pressure increased ( P < 0.001) and SV ( P = 0.012) decreased in the tall group only. In conclusion, during +2Gz, MAP increased in both short and tall males, with no difference between the groups. However, in the tall group, HR increased more during +2Gz, which could be caused by a larger hydrostatic pressure gradient from heart to head, leading to greater inhibition of the carotid baroreceptors.

In young individuals, oral free fatty acid delays gastric emptying, promotes gut hormone release, and reduces energy intake more than an isocaloric load of triglyceride does. The objective of this study was to compare the effects of the free fatty acid oleic acid (OA) and the triglyceride olive oil (OO) on gastrointestinal motility, gut hormone secretion, and energy intake in older and middle-aged healthy volunteers. In a double-blind, randomized, cross-over, study 10 older (age 83.0 ± 3.4 (mean ± SD) years) and 10 middle-aged (age 43.1 ± 8.9 years) men were examined on two occasions to evaluate the effect of isocaloric and isovolaemic loads of radiolabelled OA or OO on gastric emptying, oro-caecal transit, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretions, and energy intake. Gastric emptying was slower in older than in middle-aged men (lipid p 0.001, water p = 0.010), while no difference between these groups was found for oro-caecal transit. In comparison with OO, OA caused slower gastric emptying (lipid p 0.001, water p = 0.020) and faster oro-caecal transit (p = 0.025). Postprandial secretion of GLP-1 and PYY was comparable for older and middle-aged men, as well as for OA and OO. Older men ingested less energy than middle-aged men did (p 0.001) and their energy intake was lower after OA than OO (p = 0.002). Thus, gastric emptying of an oral lipid load is slower in older than in middle-aged men; gastric emptying is slower and oro-caecal transit faster after OA than OO in both age groups; and older men ingest less energy than middle-aged men and less energy after OA than OO.

Objective To examine 24-h blood pressure (24BP), systemic haemodynamics and the effect of sodium intake on 24BP in obese patients before and after gastric bypass surgery [laparoscopic Roux-en-Y gastric bypass (LRYGB)], and to determine whether weight loss from LRYGB might be related to an increase in plasma concentrations of atrial natriuretic peptide. Methods Twelve hypertensive and 12 normotensive morbidly obese patients underwent LRYGB: 24BP, systemic haemodynamics and mid-regional pro-atrial natriuretic peptide (MRproANP) were assessed before, 6 weeks and 12 months after surgery. The effect of high versus low sodium intake on 24BP was evaluated before and 12 months after LRYGB. Results Six weeks after LRYGB, the average weight loss was 20 kg, with a further 21 kg weight loss 1 year after surgery. In hypertensive patients, 24BP was significantly reduced at 6 weeks, but not 1 year after LRYGB. However, antihypertensive medications were successively reduced from baseline to 1 year after surgery. In normotensive patients, there was no change in 24BP 6 weeks after LRYGB, but a tendency towards a reduction 1 year after the operation. Plasma concentrations of MRproANP were subnormal prior to surgery in hypertensive patients and increased by 77% 1 year after the operation. In normotensive patients, preoperative concentrations were normal and increased only by 6%. High sodium intake induced plasma volume expansion, increased stroke volume and cardiac output, but no significant change in 24BP - neither before nor after LRYGB. Conclusions LRYGB resulted in a significant 24BP reduction and a substantial increase in MRproANP plasma concentrations in hypertensive, obese patients 6 weeks after surgery, suggesting a causal link between obesity-hypertension and altered release/degradation of cardiac natriuretic peptides.

To investigate how fluid shifts, blood pressure and systemic vascular resistance adapt to long duration (3-6 months) spaceflight.

© 2014 The Authors European Journal of Heart Failure © 2014 European Society of Cardiology. Aims: Plasma volume (PV) expansion hallmarks worsening chronic heart failure (CHF) but no non-invasive means of quantifying volume status exists. Because weight and haematocrit are related to PV, they can be used to calculate relative PV status (PVS). We tested the validity and prognostic utility of calculated PVS in CHF patients. Methods and results: First, we evaluated the agreement between calculated actual PV (aPV) and aPV levels measured using 125 Iodine-human serum albumin. Second, we derived PVS as: [(calculated aPV - ideal PV)/ideal PV] x 100%. Third, we assessed the prognostic implications of PVS in 5002 patients from the Valsartan in Heart Failure Trial (Val-HeFT), and validated this in another 246 routine CHF outpatients. On analysis, calculated and measured aPV values correlated significantly in 119 normal subjects and 30 CHF patients. In the Val-HeFT cohort, mean (+SD) PVS was -9 ± 8% and related to volume biomarkers such as brain natriuretic peptide (BNP). Over 2 years, 977 (20%) patients died. Plasma volume status was associated with death and first morbid events in a 'J-shaped' fashion with the highest risk seen with a PVS > -4%. Stratification into PVS quartiles confirmed that a PVS > -4% was associated with increased mortality (unadjusted hazard ratio 1.65, 95% confidence interval 1.44-1.88, χ 2 = 54, P < 0.001) even after adjusting for 22 variables, including brain natriuretic peptide. These results were mirrored in the validation cohort. Conclusions: Relative PVS calculated from simple clinical indices reflects the degree to which patients have deviated from their ideal PV and independently relates to outcomes. The utility of PVS-driven CHF management needs further evaluation.

The hydrostatic indifference point (HIP; where venous pressure is unaffected by posture) is located at the level of the diaphragm and is believed to indicate the orthostatic redistribution of blood, but it remains unknown whether HIP coincides with the indifference point for blood volume (VIP). During graded (± 20°) head-up (HUT) and head-down tilt (HDT) in 12 male volunteers, we determined HIP from central venous pressure and VIP from redistribution of both blood, using ultrasound imaging of the inferior caval vein (VIPui), and fluid volume, by regional electrical admittance (VIPadm). Furthermore, we evaluated whether inflation of medical antishock trousers (to 70 mmHg) affected HIP and VIP. Leaving cardiovascular variables unaffected by tilt, HIP was located 7 ± 4 cm (mean ± SD) below the 4th intercostal space (IC-4) during HUT and was similar (7 ± 3 cm) during HDT and higher ( P < 0.0001) than both VIPui (HUT: 22 ± 16 cm; HDT: 13 ± 7 cm) and VIPadm (HUT: 29 ± 9 cm; HDT: 20 ± 9 cm below IC-4). During HUT antishock trousers elevated both HIP and VIPui [to 3 ± 5 cm ( P = 0.028) and 17 ± 7 cm below IC-4 ( P = 0.051), respectively], while VIPadm remained unaffected. By simultaneous recording of pressure and filling of the inferior caval vein as well as fluid distribution, we found HIP located corresponding to the diaphragm while VIP was placed low in the abdomen, and that medical antishock trousers elevated both HIP and VIP. The low indifference point for volume shows that the gravitational influence on distribution of blood is more profound than indicated by the indifference point for venous pressure.

Recently, it has been proposed, that the blood pressure (BP) lowering effect of gastric bypass surgery not only is explained by the obtained weight loss, but that the anatomical rearrangement of the gut after ‘malabsorptive’ surgical techniques, such as the laparoscopic Roux-en-Y gastric bypass (LRYGB), may affect BP through a change in a putative 'entero-renal' axis. If so one could anticipate a reduction in BP even before a noticeable weight loss was obtained. The purpose of the present study was to investigate the very early BP response to LRYGB surgery. Ten severely obese hypertensive (mean BMI 40.8 kg/m2) and 10 severely obese normotensive (mean BMI 41.7 kg/m2) patients underwent 24-h ambulatory blood pressure measurements (24 h ABPMs) before LRYGB and again day 1 and day 10 after LRYGB. No change in 24 h BP was observed day 1 after LRYGB. Day 10 after surgery both hypertensive and normotensive patients demonstrated a significant 12.6 mmHg and 9.5 reduction in systolic BP (SBP), respectively....

Summary Background & aims In lean subjects, free fatty acid (FFA) promotes gut hormone release, delays gastric emptying, and reduces appetite and energy intake more than an isocaloric load of triglyceride (TG). In obesity, the gastrointestinal sensitivity to lipids may be reduced. Therefore, we compared the effects of the FFA oleic acid and the TG olive oil on gut hormone secretion, gastric emptying, appetite, and energy intake in lean and overweight/obese subjects. Methods In a double-blind, randomized cross-over study, 8 lean and 13 overweight/obese healthy subjects were examined at two occasions to evaluate the effect of intragastric isocaloric loads of radiolabelled oleic acid or olive oil on gastric emptying, plasma CCK, PYY, and GLP-1 concentrations, appetite, and energy intake. Results In comparison to olive oil, oleic acid caused a slower gastric emptying (p Conclusion An intragastric load of FFA is followed by slower gastric emptying, increased CCK and PYY secretion, and a lesser subsequent energy intake than an isocaloric load of TG in both lean and overweight/obese healthy subjects.

The hypothesis was tested that the cardiovascular changes during an upper body anti-orthostatic maneuver in humans are more pronounced in tall than in short individuals, because of the larger intravascular hydrostatic pressure gradients. In 34 males and 41 females [20–30 yr, body height (BH) = 147–206 cm], inter-individual multiple linear regression analyses adjusted for gender and body weight were conducted between changes in cardiovascular variables versus BH during tilting of the upper body from vertical to horizontal while keeping the legs horizontal. In all the subjects, tilting induced increases in stroke volume and arterial pulse pressure and a decrease in heart rate, which each correlated significantly with BH. In males ( n = 51, BH = 163–206 cm), 24-h ambulatory mean arterial pressure increased significantly with BH ( P = 0.004, r = 0.40, α = 0.15 mmHg/cm) so that systolic/diastolic blood pressure increased by 2/2 mmHg per 15 cm increase in BH. There was no significant correlation between mean arterial pressure and BH in females ( n = 53, BH = 147–193 cm). In conclusion, a larger BH induces larger cardiovascular changes during anti-orthostatic tilting, and in males 24-h ambulatory mean arterial pressure increases with BH. The lack of a mean arterial pressure to BH correlation in females is probably because of their lower BH and greater variability in blood pressure.

Based on previous water immersion results, we tested the hypothesis that the acute 0-G-induced increase in cardiac output (CO) is primarily caused by redistribution of blood from the vasculature above the legs to the cardiopulmonary circulation. In seated subjects ( n = 8), 20 s of 0 G induced by parabolic flight increased CO by 1.7 ± 0.4 l/min ( P < 0.001). This increase was diminished to 0.8 ± 0.4 l/min ( P = 0.028), when venous return from the legs was prevented by bilateral venous thigh-cuff inflation (CI) of 60 mmHg. Because the increase in stroke volume during 0 G was unaffected by CI, the lesser increase in CO during 0 G + CI was entirely caused by a lower heart rate (HR). Thus blood from vascular beds above the legs in seated subjects can alone account for some 50% of the increase in CO during acute 0 G. The remaining increase in CO is caused by a higher HR, of which the origin of blood is unresolved. In supine subjects, CO increased from 7.1 ± 0.7 to 7.9 ± 0.8 l/min ( P = 0.037) when entering 0 G, which was solely caused by an increase in HR, because stroke volume was unaffected. In conclusion, blood originating from vascular beds above the legs can alone account for one-half of the increase in CO during acute 0 G in seated humans. A Bainbridge-like reflex could be the mechanism for the HR-induced increase in CO during 0 G in particular in supine subjects.

Aims In patients with heart failure (HF), the use of diuretics may be a double-edged sword that can alleviate symptoms of congestion, but also result in over-diuresis and intravascular volume depletion. The purpose of the present study was to examine plasma volume (PV) in HF patients receiving from 0 to 160 mg of furosemide and to investigate whether determination of plasma N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) concentrations can predict PV-status. Methods and results Plasma volume, extracellular volume, glomerular filtration rate, NT-proBNP, and daily renal sodium excretion were measured in 18 patients with medically treated, compensated HF and in 27 healthy volunteers. Cardiac function was examined by non-invasive cardiac output determination and echocardiography. Exercise capacity was evaluated by 6 min walk test. There was a borderline significant difference in PV between patients with HF and control subjects (37.3 ± 6.0 and 40.2 ± 5.8 mL/kg, respectively, P = 0.092) with a significant tendency towards a contraction of PV with increasing use of diuretics (P = 0.031). There was no difference in extracellular volume between patients with HF and control subjects (P = 0.844). NT-proBNP plasma concentrations had no correlation to either sodium excretion (P = 0.193) or PV (P = 0.471) in patients with HF. Conclusion Plasma volume in patients with HF was within normal limits, but patients treated with high doses of loop-diuretics tended to have subnormal PV. Single measurement of NT-proBNP plasma concentration could not be used to estimate intravascular volume status in patients with HF.

The aim of this study was to evaluate an algorithm that estimates changes in cardiac output (CO) from right ventricular (RV) pressure waveforms derived from an implantable hemodynamic monitor (IHM) in heart failure patients.Twelve heart failure patients (NYHA II-III, EF 32%) with an implantable hemodynamic monitor (Chronicle) were included in this study. Changes in cardiac output were provoked by body position change at rest (left lateral supine, horizontal supine, sitting, and standing) and a steady state bicycle exercise at 20 watts. Estimated CO derived from the IHM (CO(IHM)) was compared to CO measured with inert gas rebreathing (CO(RB)), echocardiography (CO(ECHO)) and impedance cardiography (CO(ICG)). CO(RB) was considered the reference method.The median intra-patient correlation coefficient comparing CO(RB) and CO(IHM) was 0.83 (range: 0.63-0.98). Comparing CO(RB) with CO(ECHO) and CO(ICG) resulted in mean intra-patient correlation coefficients of 0.73 (-0.29-0.94) and 0.63 (-0.29-0.96). In a statistical model where slope and intercept was considered random between patients the coefficient of determination (R2) comparing CO(RB) and CO(IHM) was 0.91. Mean bias was -0.39 L/min (11%). Limits of agreement were +/-1.56 L/min and relative error was 21%.A simple algorithm based on RV pressure wave form characteristics derived from an IHM can be used to estimate changes in CO in heart failure patients. These findings encourage further research aiming to improve and validate the algorithm.

Udgivelsesdato: maj 2006 Patients with untreated heart failure (HF) exhibit a blunted hemodynamic and neuroendocrine response to a high sodium intake, leading to excessive sodium and water retention. However, it is not known whether this is the case for patients with compensated HF receiving angiotensin-converting enzyme inhibitors and beta-adrenoreceptor blockers. Therefore, we determined the hemodynamic and neuroendocrine responses to 1 wk of a low-sodium diet (70 mmol/day) and 1 wk of a high-sodium diet (250 mmol/day) in 12 HF patients and 12 age-matched controls in a randomized, balanced fashion. During steady-state conditions, hemodynamic and neuroendocrine examinations were performed at rest and during bicycle exercise. In seated HF patients, high sodium intake increased body weight (1.6 +/- 0.4%), plasma volume (9 +/- 2%), cardiac index (14 +/- 6%), and stroke volume index (21 +/- 5%), whereas mean arterial pressure was unchanged. Therefore, the total peripheral resistance decreased by 10 +/- 4%. Similar hemodynamic changes were observed during an incremental bicycle exercise test. Plasma concentrations of angiotensin II and norepinephrine were suppressed, whereas plasma pro-B-type natriuretic peptide remained unchanged. In conclusion, high sodium intake was tolerated without any excessive sodium and water retention in medically treated patients with compensated HF. The observation that high sodium intake improves cardiac performance, induces peripheral vasodilatation, and suppresses the release of vasoconstrictor hormones does not support the advice for HF patients to restrict dietary sodium.

One of the most important methodological problems of the foreign gas rebreathing technique is that outcome of the measurements depends on procedural variables such as rebreathing frequency (RF), rebreathing bag volume (V(reb)), lung volume at start of rebreathing and intervals between measurements. Therefore, in 10 healthy males we investigated the effects of changes in ventilation pattern on cardiac output (CO) estimated by an N(2)O-rebreathing technique. Reducing the rebreathing volume (V(reb)) from 1.5 to 1.0 l diminished CO by 0.5 +/- 0.2 l min(-1), whereas an increase in V(reb) from 1.5 to 2.5 l had no effects. CO was 1.0 +/- 0.2 l min(-1) higher when, rebreathing was performed after a forced expiration than following a normal tidal expiration. Serial determinations of CO required a 3-min interval between the measurements to avoid effects of recirculation of N(2)O. Changing RF from 15 to 30 breaths min(-1) or adding serial dead space by up to 600 ml did not affect the determination of CO. In conclusion, the rebreathing procedure for determination of CO at rest should be performed following a normal tidal expiration with a rebreathing bag volume of between 1.5 and 2.5 l and with manoeuvres separated by at least 3-5 min. Variations in RF within the physiological range from 15 to 30 breaths min(-1) do not affect outcome of the measurements.

An enhanced data-rates for GSM evolution (EDGE) transmitter using a nonlinear GSM-type PA is presented. It is based on a novel polar loop architecture that employs separate feedback control of the amplitude and the phase of the output signal. With this approach, the problems with AM-to-PM as well as AM-to-AM of the nonlinear PA are essentially eliminated. In addition, this architecture allows for a large dynamic output power control range, as required by the GSM specification. The transmitter uses a standard I/Q interface and does not require the extraction of amplitude and phase modulation in the digital domain. The dual feedback loop ensures robust performance even under voltage-standing wave ratio variations without using an isolator. No external PA filtering is required to meet the transmitter noise in the receive band. The EDGE spectral mask is met with an rms error vector magnitude of

Plasma volume (PV) expansion hallmarks worsening chronic heart failure (CHF) but no non-invasive means of quantifying volume status exists. Because weight and haematocrit are related to PV, they can be used to calculate relative PV status (PVS). We tested the validity and prognostic utility of calculated PVS in CHF patients.First, we evaluated the agreement between calculated actual PV (aPV) and aPV levels measured using (125)Iodine-human serum albumin. Second, we derived PVS as: [(calculated aPV - ideal PV)/ideal PV] × 100%. Third, we assessed the prognostic implications of PVS in 5002 patients from the Valsartan in Heart Failure Trial (Val-HeFT), and validated this in another 246 routine CHF outpatients. On analysis, calculated and measured aPV values correlated significantly in 119 normal subjects and 30 CHF patients. In the Val-HeFT cohort, mean (+SD) PVS was -9 ± 8% and related to volume biomarkers such as brain natriuretic peptide (BNP). Over 2 years, 977 (20%) patients died. Plasma volume status was associated with death and first morbid events in a 'J-shaped' fashion with the highest risk seen with a PVS -4%. Stratification into PVS quartiles confirmed that a PVS -4% was associated with increased mortality (unadjusted hazard ratio 1.65, 95% confidence interval 1.44-1.88, χ(2) = 54, P 0.001) even after adjusting for 22 variables, including brain natriuretic peptide. These results were mirrored in the validation cohort.Relative PVS calculated from simple clinical indices reflects the degree to which patients have deviated from their ideal PV and independently relates to outcomes. The utility of PVS-driven CHF management needs further evaluation.

Se metabolism in humans is not well characterised. Currently, the estimates of Se absorption, whole-body retention and excretion are being obtained from balance and tracer studies. In the present study, we used gamma camera imaging to evaluate the whole-body retention and distribution of radiolabelled selenomethionine (SeMet), the predominant form of Se present in foods. A total of eight healthy young men participated in the study. After consumption of a meal containing 4 MBq [75Se]l-SeMet ([75Se]SeMet), whole-body gamma camera scanning was performed for 45 min every hour over a 6 h period, every second hour for the next 18 h and once on each of the subsequent 6 d. Blood, urine and faecal samples were collected to determine the plasma content of [75Se]SeMet as well as its excretion in urine and faeces. Imaging showed that 87·9 (sd 3·3) % of the administered activity of [75Se]SeMet was retained within the body after 7 d. In contrast, the measured excretion in urine and faeces for the 7 d period was 8·2 (sd 1·1) % of the activity. Time–activity curves were generated for the whole body, stomach, liver, abdomen (other than the stomach and the liver), brain and femoral muscles. Gamma camera imaging allows for the assessment of the postprandial absorption of SeMet. This technique may also permit concurrent studies of organ turnover of SeMet.

Background: There is a growing body of evidence linking Chlamydia pneumoniae to the progression of coronary heart disease. Smaller studies have indicated that intervention with macrolide antibiotics might reduce coronary events in patients with cardiovascular diseases. Objective: To describe the design of a large-scale intervention study on the effects of a macrolide antibiotic on coronary events in patients with stable coronary heart disease (documented myocardial infarction and/or angina pectoris). Methods: This study is a double-blind, randomised, placebo-controlled, multicentre study with parallel groups. Patients are randomised to 14 days of treatment with clarithromycin (500 mg, once daily) or matching placebo. The follow-up period is 2 years, and the primary end point is a composite end point of death, non-fatal myocardial infarction or unstable angina pectoris, whichever occurs first. Recruitment began in October 1999 and will be completed in 2000. In total, 4,600 patients will be randomised. Prospectives: The study is powered to detect a reduction in coronary events of 20%. Also, the study will examine the question of whether the presence of a C. pneumoniae antibody titre is associated with a significantly increased risk of future coronary events. Finally, in the case of a significant outcome, it will be possible to test whether the effect is restricted to patients with C. pneumoniae antibodies only, or to a universal effect without any coherence to C. pneumoniae antibodies.

Background Many patients with morbid obesity (BMI > 40 kg/m) have hypertension. The complex pathophysiological abnormalities linking hypertension to obesity have not been fully clarified, but abnormal sodium handling could be an important mechanism. Method Therefore, we examined changes in body fluid compartments and haemodynamic responses (at rest and during exercise) after 5 days of a low-sodium diet (90 mmol/day) and 5 days of a high-sodium diet (250 mmol/day) in 12 morbidly obese, hypertensive patients; 12 morbidly obese, normotensive patients and 12 nonobese controls. Results High sodium intake as compared to low sodium intake was associated with an increase in plasma volume (obese, hypertensive patients: 5 ± 4%; obese, normotensive patients: 10 ± 11%; nonobese controls: 7 ± 6%), cardiac output (CO) (obese, hypertensive patients: 17 ± 12%; obese, normotensive patients: 20 ± 16%; nonobese controls: 13 ± 14%) and stroke volume (SV) (obese, hypertensive patients: 27 ± 26%; obese, normotensive patients: 27 ± 24%; nonobese controls: 18 ± 27%) in all three groups with no differences between the groups. Despite an increase in CO during high salt intake, 24-h blood pressure (BP) was unchanged in patients and controls as a result of a reduction in total peripheral resistance (obese, hypertensive patients: -11 ± 11%; obese, normotensive patients: -10 ± 12%; nonobese controls: -5 ± 14%). Similar changes were observed during an incremental bicycle exercise test wherein CO and SV were higher, whereas mean arterial BP was unchanged at each exercise level during high sodium intake. Conclusion Despite substantial increases in CO and SV, we did not observe any significant change in BP during high sodium intake, neither in morbid obese patients nor in lean individuals.

To identify factors contributing to the variation in weight loss after Roux-en-Y gastric bypass (RYGB). Cross-sectional study of patients with good (excess body mass index lost (EBL) >60%) and poor weight loss response (EBL 12 months after RYGB and a lean control group matched for age and gender. Sixteen patients with good weight loss response, 17 patients with poor weight loss response, and eight control subjects were included in the study. Participants underwent dual energy X-ray absorptiometry scan, indirect calorimetry and a 9 h multiple-meal test with measurements of glucose, insulin, total bile acids (TBA), glucagon-like peptide (GLP)-1, peptide YY3–36 (PYY), cholecystokinin (CCK), ghrelin, neurotensin and pancreatic polypeptide (PP) as well as assessment of early dumping and appetite. Suppression of hunger was more pronounced in the good than the poor responders in response to the multiple-meal test (P=0.006). In addition, the good responders had a larger release of GLP-1 (P=0.009) and a greater suppression of ghrelin (P=0.037) during the test, whereas the postprandial secretion of CCK was highest in the poor responders (P=0.005). PYY, neurotensin, PP and TBA release did not differ between the RYGB-operated groups. Compared with control subjects, patients had exaggerated release of GLP-1 (P

Quiz-based and collaborative teaching strategies have previously been found to be efficient for the improving meaningful learning of physiology during lectures. These approaches have, however, not been investigated during laboratory exercises. In the present study, we compared the impact of solving quizzes individually and in groups with conventional teaching on the immediate learning during a laboratory exercise. We implemented two quizzes in a mandatory 4-h laboratory exercise on baroreflex physiology. A total of 155 second-year medical students were randomized to solve quizzes individually ( intervention group I, n = 57), in groups of three to four students ( intervention group II, n = 56), or not to perform any quizzes (control; intervention group III, n = 42). After the laboratory exercise, all students completed an individual test, which encompassed two recall questions, two intermediate questions, and two integrated questions. The integrated questions were of moderate and advanced difficulty, respectively. Finally, students completed an evaluation form. Intervention group I reached the highest total test scores and proved best at answering the integrated question of advanced difficulty. Moreover, there was an overall difference between groups for student evaluations of the quality of the teaching, which was highest for intervention group II. In conclusion, solving quizzes individually during a laboratory exercise may enhance learning, whereas solving quizzes in groups is associated with higher student satisfaction.

Plasma volume assessment may be of importance in several disorders. The purpose of the present study was to compare the reliability of plasma volume measurements by technetium-labeled human serum albumin ((99m)Tc-HSA) with a simultaneously performed plasma volume determination with iodine-labeled human serum albumin ((125)I-HSA).In 15 healthy volunteers, simultaneous plasma volume measurements with (99m)Tc-HSA and (125)I-HSA were performed after ½ hour in the supine position. Blood samples were obtained 10, 15, 20, and 30 minutes after the injection for accurate retropolation from the plasma counts to time zero to correct for leakage of the isotopes from the circulation.The mean difference (bias) between plasma volume measured with (125)I-albumin and (99m)Tc-albumin was 8 ml (0.1 ml/kg) with limits of agreement (bias ±1.96 SD) ranging from -181-196 ml (-2.3-2.5 ml/kg). The tracer disappearance rate was significantly higher with (99m)Tc-albumin (-23.1±7.1%/h) than with (125)I-albumin (-6.7±3.6%/h) (p0.001).This study demonstrates that (99m)Tc-HSA can replace (125)I-HSA for single measurements of plasma volume in healthy volunteers. It needs to be emphasized however, that repeated blood sampling for 1/2 hour after injection of the tracer is required to correct for the disappearance of (99m)Tc and (99m)Tc-HSA from the circulation.

Udgivelsesdato: 2010-Apr The association observed between coronary heart disease (CHD) and Chlamydia (Chlamydophila) pneumoniae antibodies prompted, during the 1990s, several primary and secondary prevention trials with various antibiotics. In our CLARICOR trial, a randomized placebo-controlled trial in 4372 patients with stable CHD, a brief clarithromycin regimen was followed, unexpectedly, by increased long-term mortality. We now compare C. pneumoniae antibody levels at entry with population levels, with the patients' individual histories, and with their subsequent outcomes. IgG antibody levels were somewhat raised, but elevated IgA and IgG titers were unrelated to entry data (including prior acute myocardial infarction), except for an association with smoking and with not using statins. Hazards of mortality and of other outcomes tended to slightly increase with IgA and decrease with IgG titers, but the unfavorable clarithromycin effect was unrelated to antibody levels and remains unexplained. Smoking-related lung disease probably underlies the link between heart disease and increased IgG titers.

Purpose: It is difficult to evaluate the stability of the lumbar spondylodesis with metallic fixation devices by conventional imaging methods such as radiography or magnetic resonance imaging. It is unknown whether single photon emission computed tomography/computed tomography (SPECT/CT) may be useful to detect a lack of fixation of the pedicle screws and hence to predict instability of the fused vertebral segments. Materials and Methods: A retrospective analysis of 9 patients who were referred to bone scintigraphy, including combined SPECT/CT, due to persistent pain or discomfort after stabilizing lumbar surgery with metallic implants. The SPECT/CT findings were compared with observations from subsequent surgical reexploration. Results: In 6 of 9 patients, the SPECT/CT fully or partially detected the vertebral level of loose pedicle screws. Of 9 cases, 2 were considered inconclusive, whereas in 1 case loose pedicle screws were detected at a wrong vertebral level. Conclusion: SPECT/CT may be useful to detect a lack of fixation of the metallic implants, and hence instability of the spondylodesis by evaluating the focal bone mineralization activity in relation to the pedicle screws.

Udgivelsesdato: 2010-Feb In the CLARICOR trial, significantly increased cardiovascular (CV) and all-cause mortality in stable patients with coronary heart disease were observed after a short course of clarithromycin. We report on the impact of statin treatment at entry on the CV and all-cause mortality. The multicenter CLARICOR trial randomized patients to oral clarithromycin (500 mg daily; n = 2172) versus matching placebo (daily; n = 2201) for 2 weeks. Patients were followed through public databases. In the 41% patients on statin treatment at entry, no significant effect of clarithromycin was observed on CV (hazard ratio [HR], 0.68, 95% confidence interval [CI], 0.38-1.22; P = 0.20) or all-cause mortality (HR, 1.08; 95% CI, 0.71-1.65; P = 0.72) at 2.6-year follow up. In the patients not on statin treatment at entry, clarithromycin was associated with a significant increase in CV (HR, 1.90; 95% CI, 1.34-2.67; P = 0.0003; statin-clarithromycin interaction P = 0.0029) and all-cause mortality (HR, 1.33; 95% CI, 1.05-1.67; P = 0.016; statin-clarithromycin interaction P = 0.41). Multivariate analysis and 6-year follow up confirmed these results. Concomitant statin treatment in stable patients with coronary heart disease abrogated the observed increased CV mortality associated with 2 weeks of clarithromycin.

Following the development of herpes zoster vaccines and the potential socio-economic benefits hereof, it is relevant to conduct a study concerning epidemiological aspects of the disease based on a Danish population.Structured telephone interviews with 1207 persons above 50 years of age were conducted in order to determine the cumulated incidence proportion of herpes zoster in the age groups 50-66 years, 66-70 years and 71+.The cumulated incidence proportion of herpes zoster was 8.9%, 12.5%, 16.0% in the age groups 50-65 years, 65-70 years and 71+, respectively. Herpes zoster was positively associated with female sex, hypertension, hypercholesterolemia and prescription medicine; however, only the former remained significant after test in a multiple logistic regression model.Herpes zoster is common among persons who are more than 50 years old and most frequent among women.

Aims The aim of this study was to study the haemodynamic effect of atrioventricular delay (AVD) modifications within a narrow range in different body positions and during exercise in patients receiving cardiac resynchronization therapy (CRT). Methods The previously optimized AVD was shortened and prolonged by 40 ms in 27 CRT patients and 9 controls without heart failure. Cardiac output (CO) was measured by inert gas rebreathing (Innocor) as the average over different body positions (left-lateral, supine, sitting, standing, and exercise). In eight CRT patients with an implantable haemodynamic monitor, the estimated pulmonary artery diastolic pressure (ePAD) was analysed. Results The magnitude of CO response to AVD changes was greater in CRT patients than in controls (0.25 vs. 0.20 L/min, P < 0.05), varied substantially between individuals (range: 0.12–0.56 L/min), and correlated with left atrial size ( r = 0.61, P < 0.001). On average, AVD shortening decreased CO slightly (0.07 ± 0.17 L/min) and increased ePAD (1.1 ± 0.8 mmHg, both P < 0.05), whereas prolongation had no significant effect. Conclusion The haemodynamic response to AVD modifications within a narrow range is larger in CRT patients than in normal controls and varies substantially between individuals. These findings suggest that optimal AVD tuning is clinically important in selected patients.

Aims Plasma B-type natriuretic peptide (BNP) and proBNP are promising markers for treatment of heart failure (HF), but the intra-individual biological variation is high. We investigated whether changes in sodium intake and posture contribute to this variation. Methods and results A total of 12 healthy individuals and 12 patients with medically treated compensated HF were examined after 1 week of low (70 mmol [1.61 g] per day) and 1 week of high (250 mmol [5.75 g] per day) sodium intake. Plasma volume and plasma concentrations of BNP and proBNP were determined after 1 h in seated and 1 h in supine position. In healthy individuals, the plasma BNP concentration increased significantly on high sodium intake with a ratio (high sodium/low sodium) of 2.00 (1.32–3.03, P = 0.004). The corresponding values for HF patients were 1.69 (1.25–2.29, P = 0.003). The plasma BNP concentration changed modestly by a posture change, with a plasma BNP ratio (supine/seated) of 1.15 (1.07–1.14, P = 0.001) and 1.06 (0.99–1.24, P = 0.088) in healthy subjects and HF patients, respectively. Plasma proBNP concentrations were neither significantly affected by posture nor by sodium intake. Conclusion Sodium intake has a considerable effect on plasma BNP and therefore contributes to the intra-individual variability. We suggest dietary sodium intake to be standardized at least 3 days prior to blood sampling for the determination of plasma BNP.

Objectives: We have reported increased 2.6-year mortality in clarithromycin- versus placebo-exposed stable coronary heart disease patients, but meta-analysis of randomized trials in coronary heart disease patients showed no significant effect of antibiotics on mortality. Here we report the 6-year mortality of clarithromycin- versus placebo-exposed patients and updated meta-analyses. Methods: Centrally randomized, placebo controlled multicenter trial. All parties were blinded. Analyses were by intention to treat. Meta-analyses followed the Cochrane Collaboration methodology. Results: We randomized 4,372 patients with stable coronary heart disease to clarithromycin 500 mg (n = 2,172) or placebo (n = 2,200) once daily for 2 weeks. Mortality was followed through public register. Nine hundred and twenty-three patients (21.1%) died. Six-year mortality was significantly higher in the clarithromycin group (hazard ratio 1.21, 95% confidence interval 1.06–1.38). Adjustment for entry characteristics (sex, age, prior myocardial infarction, center, and smoking) did not change the results (1.18, 1.04–1.35). Addition of our data to that of other randomized trials on antibiotics for patients with coronary heart disease versus placebo/no intervention (17 trials, 25,271 patients, 1,877 deaths) showed a significantly increased relative risk of death from antibiotics of 1.10 (1.01–1.20) without heterogeneity. Conclusions: Our results stress the necessity to consider carefully the strength of the indication before administering antibiotics to patients with coronary heart disease.

During everyday life, gravity constantly stresses the cardiovascular system in upright humans by diminishing venous return. This decreases cardiac output and induces systemic vasoconstriction to prevent blood pressure from falling. We therefore tested the hypothesis that entering weightlessness leads to a prompt increase in cardiac output and to systemic vasodilatation and that these effects persist for at least a week of weightlessness in space. Cardiac output and mean arterial pressure were measured in 8 healthy humans during acute 20-s periods of weightlessness in parabolic airplane flights and on the seventh and eighth day of weightlessness in 4 astronauts in space. The seated 1-G position acted as reference. Entering weightlessness promptly increased cardiac output by 29±7%, from 6.6±0.7 to 8.4±0.9 L min −1 (mean±SEM; P =0.003), whereas mean arterial pressure and heart rate were unaffected. Thus, systemic vascular resistance decreased by 24±4% ( P =0.017). After a week of weightlessness in space, cardiac output was increased by 22±8% from 5.1±0.3 to 6.1±0.1 L min −1 ( P =0.021), with mean arterial pressure and heart rate being unchanged so that systemic vascular resistance was decreased by 14±9% ( P =0.047). In conclusion, entering weightlessness promptly increases cardiac output and dilates the systemic circulation. This vasorelaxation persists for at least a week into spaceflight. Thus, it is probably healthy for the human cardiovascular system to fly in space.

Recent trends in the integration of entire systems on-chip have spurred the development of homodyne radios as alternatives to the more mature yet harder to integrate superheterodyne architectures. This paper presents a monolithic device that integrates all of the functions necessary to implement a multiband homodyne global system for mobile telecommunications (GSM) radio except for the power amplifier (PA) and radio frequency (RF) passives. The single BiCMOS chip includes a quad-band direct conversion receiver that down converts RF to quadrature analog baseband. The front-end circuitry is followed by a low-DC-offset, high-dynamic-range, analog I/Q baseband chain. The transmit section is comprised of a quad-band up-conversion transmit phase-locked loop (PLL) including on chip transmit voltage-controlled oscillators (VCOs). The stringent GSM receive band phase noise specifications are met without the use of surface acoustic wave filters. A single /spl Sigma//spl Delta/ fractional-N synthesizer locking a fully integrated ultrahigh frequency VCO generates the system local oscillator signal.

An EDGE transmitter using a nonlinear GSM type PA is presented. It is based on a polar loop architecture that employs separate feedback control of the amplitude and the phase of the output signal. With this approach, the problems with AM-to-PM as well as AM-to-AM of the nonlinear PA are essentially eliminated. There is no mode change between GMSK and EDGE, and the transmitter operates seamlessly in multi-slot EGPRS. The polar modulation transmitter meets all the GSM type approval requirements for both EDGE and GMSK in the quad band (850/900/1800/1900 MHz). It is part of an RF subsystem which is in production.

Conventional cellular handset receiver designs place receive-band filters, usually surface acoustic wave (SAW) filters, prior to and after the low-noise amplifier (LNA). In a triple-band receiver, this amounts to six SAW filters. The device presented here also eliminates the post-LNA SAW filters, but without the excess current required by image-reject mixers. It does so through the use of passive on-chip LC image filters. This makes possible higher dynamic range with low supply current, and low noise figure while providing a greater amount of image-rejection in comparison with image-reject mixer-based solutions.

The hypothesis was tested that cardiac output (CO) and stroke volume (SV) are increased by a moderate physiological elevation in sodium intake with a more pronounced effect in the ambulatory upright seated than supine position. Fourteen healthy males were investigated during ambulatory and controlled laboratory conditions at the end of two consecutive 5-day periods with sodium intakes of 70 (low) and 250 (high) mmol/24 h or vice versa, respectively. Comparing high and low sodium intake, plasma volume and plasma protein concentrations were 9 and 8% higher in the seated and the supine position, respectively. When seated during laboratory conditions, CO was 5.3 ± 0.2 l/min on the high sodium intake vs. 4.8 ± 0.2 l/min on the low ( P < 0.05), and SV was 81 ± 3 vs. 68 ± 3 ml ( P< 0.05). In the supine position, SV was 107 ± 3 ml on the high vs. 99 ± 3 ml ( P < 0.05) on the low sodium intake, while CO remained unchanged. The difference in CO and SV induced by the change in sodium intake was significantly higher in the seated than in the supine position ( P < 0.05). During upright ambulatory conditions, CO was 5.9 ± 0.2 l/min during the high and 5.2 ± 0.2 l/min during the low sodium intake ( P < 0.05), and SV was 84 ± 3 and 69 ± 3 ml ( P < 0.05), respectively. Mean arterial pressure was unchanged by the variations in sodium intake. In conclusion, increments in sodium intake within the normal physiological range increase CO and SV and more so in the seated vs. the supine position. These changes are readily detectable during upright, ambulatory conditions. The results indicate that the higher SV and CO could constitute an arterial baroreflex stimulus for the augmented renal sodium excretion.

Values of effective pulmonary blood flow (Q(EP)) and cardiac output, determined by a non-invasive foreign gas rebreathing method (CO(RB)) using a new infrared photoacoustic gas analysing system, were compared with measurements of cardiac output obtained by the direct Fick (CO(FICK)) and thermodilution (CO(TD)) methods in patients with heart failure or pulmonary hypertension. In 11 patients, of which three had shunt flow through areas without significant gas exchange, the mean difference (bias) and limits of agreement (+/- 2 S.D.) were 0.6 +/- 1.2 litre x min(-1) when comparing CO(FICK) and Q(EP), and -0.8 +/- 1.3 litre x min(-1) when comparing CO(FICK) and CO(TD). When correction for intrapulmonary shunt flow was applied (i.e. calculation of CO(RB)) in all 11 patients, the bias between CO(FICK) and CO(RB) was 0.1 +/- 0.9 litre x min(-1), primarily because agreement improved in the three patients with significant shunt flow. In the eight patients without significant shunt flow, the agreement between Q(EP) and CO(FICK) was 0.3 +/- 0.9 litre x min(-1). In conclusion, a foreign gas rebreathing method with a new infrared photoacoustic gas analyser provided at least as reliable a measure of cardiac output as did thermodilution. In the absence of significant shunt flow, measurement of Q(EP) itself provides a reliable estimate of cardiac output in heart failure patients. The infrared photoacoustic gas analyser markedly facilitates clinical use of the rebreathing method in general, which makes the method available to a larger group of clinicians working with patients with cardiovascular diseases.