Pulmonary Capillary Volume Research Articles

Deciphering Alveolo-Capillary Gas Transfer Disturbances in Patients Recovering from COVID-19 Lung Disease.

Impaired lung gas exchange is commonly seen in patients with pulmonary involvement related to SARS-CoV-2 acute infection or post-acute COVID-19 syndrome (PACS). The primary aim of our study was to assess lung gas transfer, measuring the pulmonary diffusion capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) in all COVID-19 patients. Our secondary aim was to decipher the respective roles of perturbed lung membrane conductance (DM) and reduced pulmonary capillary volume (VC) in patients with impaired lung gas exchange. From May to October 2020, we measured DLNO-DLCO in 118 patients during their post-COVID-19 period (4.6 months after infection) to decipher alveolo-capillary gas transfer disturbances. DLNO-DLCO measurement was also performed in 28 healthy non-smokers as controls. Patients were classified into three groups according to the severity (mild, moderate, and severe) of acute COVID-19 infection. Patients with mild COVID-19 had normal lung volumes and airways expiratory flows but impaired pulmonary gas exchange, as shown by the significant decreases in DLNO, DLCO, DM, and VC as compared with controls. VC was significantly impaired and the DLNO/DLCO ratio was increased in patients with moderate (n = 4, 11%) and severe COVID-19 (n = 23, 49%). Abnormal membrane conductance was also seen in all three groups of post-COVID-19 patients. These findings suggest a persistent alveolo-capillary gas transfer defect, implying not only reduced membrane conductance but also abnormal pulmonary vascular capacitance in all PACS patients, even those with a milder form of COVID-19 infection.

Respiratory function in uncomplicated type 1 diabetes: Blunted during exercise even though normal at rest!

Type 1 diabetes is associated with a substantially increased risk of impaired lung function, which may impair aerobic fitness. We therefore aimed to examine the ventilatory response during maximal exercise and the pulmonary diffusion capacity function at rest in individuals with uncomplicated type 1 diabetes. In all, 17 adults with type 1 diabetes free from micro-macrovascular complications (glycated haemoglobin: 8.0 ± 1.3%), and 17 non-diabetic adults, carefully matched to the type 1 diabetes group according to gender, age, level of physical activity and body composition, participated in our study. Lung function was assessed by spirometry and measurements of the combined diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) at rest. Subjects performed a maximal exercise test during which the respiratory parameters were measured. At rest, DLCO (30.4 ± 6.1ml min-1 mmHg-1 vs. 31.4 ± 5.7ml min-1 mmHg-1 , respectively, p=0.2), its determinants Dm (membrane diffusion capacity) and Vc (pulmonary capillary volume) were comparable among type 1 diabetes and control groups, respectively. Nevertheless, spirometry parameters (forced vital capacity=4.9 ± 1.0L vs. 5.5 ± 1.0L, p < 0.05; forced expiratory volume 1=4.0 ± 0.7L vs. 4.3 ± 0.7L, p < 0.05) were lower in individuals with type 1 diabetes, although in the predicted normal range. During exercise, ventilatory response to exercise was different between the two groups: tidal volume was lower in type 1 diabetes vs. individuals without diabetes (p < 0.05). Type 1 diabetes showed a reduced VO2max (34.7 ± 6.8 vs. 37.9 ± 6.3, respectively, p=0.04) in comparison to healthy subjects. Individuals with uncomplicated type 1 diabetes display normal alveolar-capillary diffusion capacity and at rest, while their forced vital capacity, tidal volumes and VO2 are reduced during maximal exercise.

Week to week variability of pulmonary capillary blood volume and alveolar membrane diffusing capacity in patients with heart failure

BackgroundAlveolar-capillary membrane diffusing capacity for carbon monoxide (DMCO) and pulmonary capillary volume (Vcap) can be estimated by the multi-step Roughton and Foster (RF, original method from 1957) or the single-step NO–CO double diffusion technique (developed in the 1980s). The latter method implies inherent assumptions. We sought to determine which combination of the alveolar membrane diffusing capacity for nitric oxide (DMNO) to DMCO ratio, an specific conductance of the blood for NO (θNO) and CO (θCO) gave the lowest week-to-week variability in patients with heart failure. Methods44 heart failure patients underwent DMCO and Vcap measurements on three occasions over a ten-week period using both RF and double dilution NO-CO techniques. ResultsWhen using the double diffusing method and applying θNO = infinity, the smallest week-to-week coefficient of variation for DMCO was 10 %. Conversely, the RF method derived DMCO had a much greater week-to-week variability (2x higher coefficient of variation) than the DMCO derived via the NO-CO double dilution technique. The DMCO derived from the double diffusion technique most closely matched the DMCO from the RF method when θNO = infinity and DMCO = DLNO/2.42. The Vcap measured week-to-week was unreliable regardless of the method or constants used. ConclusionsIn heart failure patients, the week-to-week DMCO variability was lowest when using the single-step NO-CO technique. DMCO obtained from double diffusion most closely matched the RF DMCO when DMCO/2.42 and θNO = infinity. Vcap estimation was unreliable with either method.

Impact of increased venous pressure on kidney function and mortality in cardiovascular patients with preserved ejection fraction

Background: Right but not left ventricular hemodynamic parameters have been found to be independently associated with adverse renal outcomes in patients with acute decompensated heart failure (HF).Aim: To investigate the hemodynamic profile of patients without acute decompensated heart failure and left ventricular ejection fraction >50% referred for elective left and right heart catheterization and to correlate left and right filling pressures, stroke volume and arterial blood pressure to renal function parameters. Subsequently, we tested the hypothesis that right ventricle and left ventricle hemodynamic parameters can predict all-cause mortality in our non-HF subjects.Methods: Between October 2009 and November 2010, 151 consecutive patients referred for elective left and right heart catheterization were studied and consequently followed up for a mean period of 8 years in order to identify all-cause mortality. Patient’s initial cohort was subdivided in two groups according to right atrial pressure. The RAPRLOW group (Right Atrium Pressure ≤ 9 mmHg) and the RAPRHIGH group (Right Atrium Pressure > 9mmHg)Results: No correlation between blood pressure, pulmonary capillary wedges pressure, cardiac index, stroke volume and stroke volume index (SVI), and parameters of kidney function was observed. However, a weak, although, significant correlation between right atrial pressure (RAP) and modification of diet in renal disease (MDRD) (r = –0.202; p = .014) could be detected. RAPRLOW patients had a statistically significant lower MDRD value of 16.6 mL/min/1.73 m2 than RAPRHIGH patients. Increased RAP (HR = 2.03; 95% [CI]: 1.05 to 3.9; p = .025) and age (HR = 1.08, 95% [CI] 1.04–1.12, p < .001) independently predicted all-cause mortality during follow up.Conclusions: Our study demonstrates that right ventricular preload affects renal function in patients with preserved systolic function and that neither aortic systolic pressure nor left ventricle pressure indices were related to estimated glomerular filtration rate. Furthermore, we demonstrate for the first time that an increased RAP is able to predict a worse prognosis in patients with preserved ejection fraction independently of well-established risk factors, such as blood pressure and SVI.

Decreased pulmonary capillary volume in adolescents born very preterm.

Decreased pulmonary capillary volume in adolescents born very preterm.

Decreased pulmonary vascular distensibility in adolescents conceived by in vitro fertilization.

What is the functional relevance of decreased pulmonary vascular distensibility in adolescents conceived by IVF? Children born by IVF have a slight decrease in pulmonary vascular distensibility observed during normoxic exercise that is not associated with altered right ventricular function and aerobic exercise capacity. General vascular dysfunction and increased hypoxic pulmonary hypertension have been reported in ART children as compared to controls. Pulmonary hypertension or decreased pulmonary vascular distensibility may affect right ventricular function and thereby possibly limit maximal cardiac output and aerobic exercise capacity. This prospective case-control study enrolled 15 apparently healthy adolescents conceived by IVF/ICSI after fresh embryo transfer paired in a 2 to 1 ratio to 30 naturally conceived adolescents between March 2015 and May 2018. Fifteen IVF/ICSI adolescents and 30 controls from singleton gestations matched by age, gender, weight, height and physical activity underwent exercise echocardiography, lung diffusion capacity measurements and a cycloergometer cardiopulmonary exercise test. A pulmonary vascular distensibility coefficient α was determined from the pulmonary arterial pressure (PAP) versus cardiac output (Q) relationships. Pulmonary capillary volume (Vc) was calculated from single breath nitric oxide and carbon monoxide lung diffusion capacity measurements (DLCO and DLNO) at rest and during exercise (100W). Eight of the IVF subjects and eight controls underwent a 30min hypoxic challenge at rest with a fraction of inspired oxygen of 0.12 to assess hypoxic pulmonary vasoconstriction. In normoxia, oxygen uptake (VO2), blood pressure, DLCO, DLNO, echocardiographic indices of right ventricular function, Q and PAP at rest and during exercise were similar in both groups. However, IVF children had a lower pulmonary vascular distensibility coefficient α (1.2 ± 0.3 versus 1.5 ± 0.3%/mmHg, P= 0.02) and a blunted exercise-induced increase in Vc (24 versus 32%, P< 0.05). Hypoxic-induced increase in pulmonary vascular resistance in eight IVF subjects versus eight controls was similar. The IVF cohort was small, and thus type I or II errors could have occurred in spite of careful matching of each case with two controls. ART evolved over the years, so that it is not certain that the presently reported subtle changes will be reproducible in the future. As the study was limited to singletons born after fresh embryo transfers, our observations cannot be extrapolated to singletons born after frozen embryo transfer. The present study suggests that adolescents conceived by IVF have preserved right ventricular function and aerobic exercise capacity despite a slight alteration in pulmonary vascular distensibility as assessed by two entirely different methods, i.e. exercise echocardiography and lung diffusing capacity measurements. However, the long-term prognostic relevance of this slight decrease in pulmonary vascular distensibility needs to be evaluated in prospective large scale and long-term outcome studies. Dr Caravita was supported by an ERS PAH short term research training fellowship (STRTF2014-5264). Dr Pezzuto was funded by an Italian Society of cardiology grant. Dr Motoji was supported by a grant from the Cardiac Surgery Funds, Belgium. All authors have no conflicts of interests to declare.

Reference equations for pulmonary diffusing capacity of carbon monoxide and nitric oxide in adult Caucasians.

The aim of this study was to determine reference equations for the combined measurement of diffusing capacity of the lung for carbon monoxide (CO) and nitric oxide (NO) (DLCONO). In addition, we wanted to appeal for consensus regarding methodology of the measurement including calculation of diffusing capacity of the alveolo-capillary membrane (Dm) and pulmonary capillary volume (Vc).DLCONO was measured in 282 healthy individuals aged 18-97 years using the single-breath technique and a breath-hold time of 5 s (true apnoea period). The following values were used: 1) specific conductance of nitric oxide (θNO)=4.5 mLNO·mLblood-1·min-1·mmHg-1; 2) ratio of diffusing capacity of the membrane for NO and CO (DmNO/DmCO)=1.97; and 3) 1/red cell CO conductance (1/θCO)=(1.30+0.0041·mean capillary oxygen pressure)·(14.6/Hb concentration in g·dL-1).Reference equations were established for the outcomes of DLCONO, including DLCO and DLNO and the calculated values Dm and Vc Independent variables were age, sex, height and age squared.By providing new reference equations and by appealing for consensus regarding the methodology, we hope to provide a basis for future studies and clinical use of this novel and interesting method.

Ventilation inhomogeneity and NO and CO diffusing capacity in ex-premature school children

Ex-premature school children show mild-to-moderate airway obstruction and decreased CO diffusing capacity. Multiple breath nitrogen washout (N2MBW) and NO diffusing capacity (DLNO) measurements may provide new insight into long-term pulmonary and vascular impairment in bronchopulmonary dysplasia (BPD). We examined a randomly selected group of 70 ex-premature children (gestational age <28 weeks or birth weight <1500 g; 42 with and 28 without BPD) and 38 term-born healthy controls of 8-13 years of age. Subjects performed N2MBW (lung clearance index, LCI; Sacin, and Scond), DLNO (membrane related diffusing capacity, Dm and pulmonary capillary volume, Vc), Fractional exhaled NO, CO diffusing capacity, conventional spirometry (FEV1, FVC, FEF25-75) and plethysmography (RV, TLC). Respiratory symptoms were assessed by questionnaire. Compared to healthy controls, the BPD group had higher z-scores for lung clearance index (P = 0.003), Sacin (P = 0.005), lower CO diffusing capacity (P = 0.025), DLNO (P = 0.022), DLNO/VA z-scores (P = 0.025) and a significant larger proportion had respiratory complaints. Amongst ex-premature children, the BPD group did not differ from the non-BPD group except for a decreased Dm (P = 0.023). Ex-premature with BPD showed predominantly airway obstruction (FEV1/FVC; P < 0.0001), signs of hyperinflation (RV/TLC-ratio; P = 0.028), and 25% had a positive bronchodilator response (>12% in FEV1). Ex-premature school children exhibited relatively mild but significant long-term respiratory symptoms and pulmonary peripheral impairment judged by N2MBW and DLNO measurements along with well-known airway obstruction. Larger longitudinal studies are needed to assess the clinical use of these advanced methods of assessing ventilation inhomogeneity and DLNO.

Altered pulmonary gas transfer capacity and capillary blood volume in pediatric Crohn's disease.

To describe diffusing capacity for carbon monoxide (DLCO) and its components, that is, membrane diffusing capacity (DmCO) and pulmonary capillary blood volume (Vc) in children with Crohn's disease (CD), and to investigate the correlation between these parameters and disease activity. The most common lung function abnormalities are a reduced pulmonary DLCO and small airways disorders which are in many instances, clinically silent. No valid explanations have been proposed regarding the modifications in gas transfer capacity in active CD. DLCO, DmCO, and Vc were measured in 25 CD children by the simultaneous single breath lung diffusing capacity method using nitric oxide (NO) and carbon monoxide (CO) transfer. These parameters were analyzed in relation to the CD disease activity index. DLCO (90.7 ± 4.5% vs 128.5 ± 4.7%; P < 0.001), Dm (92.4 ± 5.9% vs 125.6 ± 6.3%; P < 0.001), and Vc (72.6 ± 3.7% vs 104.4 ± 4.0%; P < 0.001) were significantly decreased in the active CD group in comparison with the inactive CD group. DLCO (r = -0.60; P < 0.01), DmCO (r = -0.45; P < 0.01), and Vc (r = -0.60; P < 0.01) were inversely correlated to the PCDAI. In 8 patients who participated to the study at initial diagnosis then during remission, DmCO and Vc increased significantly between the active and the inactive period of the disease. Pulmonary diffusing capacity is impaired in children with active CD, mainly because of a decrease of the pulmonary capillary volume.

Lung diffusing capacity for nitric oxide as a marker of fibrotic changes in idiopathic interstitial pneumonias.

Lung diffusing capacity for carbon monoxide (DLCO) is decreased in both usual interstitial pneumonia-idiopathic pulmonary fibrosis (UIP-IPF) and nonspecific interstitial pneumonia (NSIP), but is moderately related to computed tomography (CT)-determined fibrotic changes. This may be due to the relative insensitivity of DLCO to changes in alveolar membrane diffusive conductance (DMCO). The purpose of this study was to determine whether measurement of lung diffusing capacity for nitric oxide (DLNO) better reflects fibrotic changes than DLCO DLNO-DLCO were measured simultaneously in 30 patients with UIP-IPF and 30 with NSIP. Eighty-one matched healthy subjects served as a control group. The amount of pulmonary fibrosis was estimated by CT volumetric analysis of visually bounded areas showing reticular opacities and honeycombing. DMCO and pulmonary capillary volume (VC) were calculated. DLNO was below the lower limit of normal in all patients irrespective of extent and nature of disease, whereas DLCO was within the normal range in a nonnegligible number of patients. Both DLNO and DLCO were significantly correlated with visual assessment of fibrosis but DLNO more closely than DLCO DMCO was also below the lower limit of normal in all UIP-IPF and NSIP patients and significantly correlated with fibrosis extent in both diseases, whereas VC was weakly correlated with fibrosis in UIP-IPF and uncorrelated in NSIP, with normal values in half of patients. In conclusion, measurement of DLNO may provide a more sensitive evaluation of fibrotic changes than DLCO in either UIP-IPF or NSIP, because it better reflects DMCO.

Atrial function in heart transplant recipients operated with the bicaval technique

Objectives: In heart transplantation (HTx) with the bicaval technique the whole right atrium (RA) is donor tissue while the left atrium (LA) consists of both donor and recipient tissue. The aims of the study were to describe atrial function in comparison with healthy controls and to identify determinants of dysfunction. Design: Forty-three patients and 30 controls were retrospectively included. Echocardiography was performed within 24 h of right heart catheterization (RHC) (HTx recipients). Results: The peak longitudinal atrial systolic strain (ɛ) described the atrial reservoir function. The LA and RA reservoir function were reduced versus controls (LA-ɛ 18 ± 8 versus 44 ± 10%; RA-ɛ 22 ± 10 versus 69 ± 17%, p < 0.001). There were moderate relationships between atrial-ɛ and ventricular filling pressure (r = −0.64 for LA-ɛ; r = −0.57 for RA-ɛ). In a multiple regression analysis the LA-ɛ was determined by pulmonary capillary wedge pressure (PCWP) and LA minimum volume index (r = −0.71) while RA-ɛ was dependent on the right ventricular ɛ (r = −0.77). Conclusions: Atrial reservoir function is markedly reduced in HTx recipients related to elevated PCWP and LA-enlargement in the LA and in the RA impaired longitudinal right ventricular function.

The single-breath diffusing capacity of CO and NO in healthy children of European descent.

RationaleThe diffusing capacity (DL) of the lung can be divided into two components: the diffusing capacity of the alveolar membrane (Dm) and the pulmonary capillary volume (Vc). DL is traditionally measured using a single-breath method, involving inhalation of carbon monoxide, and a breath hold of 8–10 seconds (DL,CO). This method does not easily allow calculation of Dm and Vc. An alternative single-breath method (DL,CO,NO), involving simultaneous inhalation of carbon monoxide and nitric oxide, and traditionally a shorter breath hold, allows calculation of Dm and Vc and the DL,NO/DL,CO ratio in a single respiratory maneuver. The clinical utility of Dm, Vc, and DL,NO/DL,CO in the pediatric age range is currently unknown but also restricted by lack of reference values.ObjectivesThe aim of this study was to establish reference ranges for the outcomes of DL,CO,NO with a 5 second breath hold, including the calculated outcomes Dm, Vc, and the DL,NO/DL,CO ratio, as well as to establish reference values for the outcomes of the traditional DL,CO method, with a 10 second breath hold in children.MethodsDL,CO,NO and DL,CO were measured in healthy children, of European descent, aged 5–17 years using a Jaeger Masterscreen PFT. The data were analyzed using the Generalized Additive Models for Location Scale and Shape (GAMLSS) statistical method.Measurements and Main ResultsA total of 326 children were eligible for diffusing capacity measurements, resulting in 312 measurements of DL,CO,NO and 297 of DL,CO, respectively. Reference equations were established for the outcomes of DL,CO,NO and DL,CO, including the calculated values: Vc, Dm, and the DL,NO/DL,CO ratio.ConclusionThese reference values are based on the largest sample of children to date and may provide a basis for future studies of their clinical utility in differentiating between alterations in the pulmonary circulation and changes in the alveolar membrane in pediatric patients.

Prior maximal exercise decreases pulmonary diffusing capacity during subsequent exercise.

Pulmonary diffusion (DLCO) increases during exercise due to greater pulmonary capillary volume (Vc) and membrane diffusing capacity (DM). However, after heavy exercise there is a reduction in resting DLCO. It is unclear whether this post-exercise effect will attenuate the normal increase in DLCO, Vc and DM during subsequent exercise and whether this affects SpO2 (pulse oximeter). DLCO, Vc, DM, cardiac output and SpO2 were measured at rest, moderate (~70% VO2peak) and heavy (~90 VO2peak) exercise in 9 subjects during 2 sessions separated by ~90 min. DLCO, Vc and DM increased during exercise (P<0.05). DLCO (P<0.05) and Vc (P<0.10), but not DM or SpO2 were lower in session 2 compared to the first. Reductions in DLCO and Vc appeared to be smallest during rest (1-4%) and greatest at high-intensity exercise (8-20%), but the interaction was not significant. SpO2 decreased by 4.9% and 5.1% from rest to high-intensity exercise during the first and second exercise bout, but these changes were not different. These data confirm that a bout of high-intensity exercise reduces DLCO and Vc, and may indicate that these changes are exacerbated during subsequent high-intensity exercise. Despite these changes, SpO2 was not affected by previous exercise.

Capnodynamic Estimation of Lung Volumes: Teething Issues of a Potential Early Warning System

I would like to commend Albu et al.1 for their well-designed study evaluating the correlation between effective lung volume (ELV) and end-expiratory lung volume (EELV) in healthy and surfactant-depleted rabbit lungs with various levels of positive end-expiratory pressure.The results have indicated that the correlation between ELV and EELV improves with higher positive end-expiratory pressure, and is best in surfactant-depleted lungs, with the ELV being an overestimate of ELV in healthy lungs by as much as 150 ± 13% at 0 cm H2O. The authors have hypothesized that this is due to carbon dioxide being an intrinsic gas and the ELV/EELV difference is affected by changes in pulmonary capillary volume and ventilation–perfusion mismatch. There are other methodological factors that may affect this correlation, but no method is able to satisfactorily correct for those, and any attempt may potentially require a more complicated set-up than the elegant one Albu et al. propose.2However, for neonatal patients (whom a rabbit model is supposed to simulate), lung injury is on a continuum from healthy to surfactant-depleted. Generally a surfactant-depleted state is avoided by the following two interventions—antenatal glucocorticoid therapy and the instillation of exogenous surfactant into the neonatal lung. Therefore, most neonates requiring ventilator support for perioperative or critical care will be somewhere in the middle—having neither healthy nor surfactant-depleted lungs. The lack of demonstrable reliability of ELV in this gray zone undermines the utility of its absolute value as an estimation of the EELV in this setting.The authors imply that trending the change in ELV would be more useful than the absolute value. I would be concerned however that the percentage change in ELV and EELV postlavage differs significantly between different positive end-expiratory pressure values. The difference is greatest at 0 and 9 cm H2O, but this mitigates the issue somewhat because an optimal and protective lung ventilation strategy in neonates is unlikely to be at these extremes. Nevertheless, it may be difficult to estimate the degree of change in actual lung volumes after a decrease in ELV, and may lead a provider to utilize an overly aggressive recruitment strategy that could potentially result in barotrauma.It should be noted that the sensitivity of ELV to changes to effectiveness in ventilation and as a rough measure of physiological dead space could be useful when paired with other indices that together may indicate lung dysfunction.3 For example, a decreasing ELV with increasing airway resistance and pressures can serve as a preliminary warning before an appreciable increase in ETco2 or a suboptimal arterial blood gas result. At present, such dysfunction is only detected after an arterial blood gas result, and there is no simple, continuous and noninvasive method to detect lung atelectasis and institute recruitment measures early.I believe the greatest value of this study is that the method they describe can be easily implemented as part of an early warning protocol for recruitment manoeuvres, and then a gauge of the effectiveness of the intervention.3 Further studies and modification of the algorithm should be done to improve the accuracy of ELV as an estimate of EELV in various lung states and ventilator settings. This may then allow its potential to be realized as a simple yet powerful tool currently absent from the arsenal available to modern anesthesiologists and intensivists.The author declares no competing interests.

Mechanisms for reduced pulmonary diffusing capacity in haematopoietic stem-cell transplantation recipients

Lung diffusing capacity for CO (DLCO) is compromised in haematopoietic stem-cell transplantation (HSCT) recipients. We derived alveolar–capillary membrane conductance (DM,CO) and pulmonary capillary volume (VC) from DLCO and diffusing capacity for NO (DLNO). Forty patients were studied before and 6 weeks after HSCT. Before HSCT, DLNO and DLCO were significantly lower than in 30 healthy controls. DM,CO was ∼40% lower in patients than in controls (p<0.001), whereas VC did not differ significantly. After HSCT, DLNO and DM,CO further decreased, the latter by ∼22% from before HSCT (p<0.01) while VC did not change significantly. Lung density, serum CRP and reactive oxygen metabolites were significantly increased, with the latter being correlated (R2=0.71, p<0.001) with the decrement in DLNO. We conclude that DLNO and, to a lesser extent, DLCO are compromised before HSCT mainly due to a DM,CO reduction. A further reduction of DM,CO without VC loss occurs after HSCT, possibly related to development of oedema, or interstitial fibrosis, or both.

New insights into the mechanisms involved in B-type natriuretic peptide elevation and its prognostic value in septic patients.

IntroductionElevated plasma B-type natriuretic peptide (BNP) levels in patients with critical sepsis (severe sepsis and septic shock) may indicate septic cardiomyopathy. However, multiple heterogeneous conditions may also be involved in increased BNP level. In addition, the prognostic value of BNP in sepsis remains debatable. In this study, we sought to discover potential independent determinants of BNP elevation in critical sepsis. The prognostic value of BNP was also evaluated.MethodsIn this observational study, we enrolled mechanically ventilated, critically septic patients requiring hemodynamic monitoring through a pulmonary artery catheter. All clinical, laboratory and survival data were prospectively collected. Plasma BNP concentrations were measured daily for five consecutive days. Septic cardiomyopathy was assessed on day 1 on the basis of left and right ventricular ejection fractions (EF) derived from echocardiography and thermodilution, respectively. Mortality was recorded at day 28.ResultsA total of 42 patients with severe sepsis (N = 12) and septic shock (N = 30) were ultimately enrolled. Daily BNP levels were significantly elevated in septic shock patients compared with those with severe sepsis (P ≤0.002). Critical illness severity (assessed by Acute Physiology and Chronic Health Evaluation II and maximum Sequential Organ Failure Assessment scores), and peak noradrenaline dose on day 1 were independent determinants of BNP elevation (P <0.05). Biventricular EFs were inversely correlated with longitudinal BNP measurements (P <0.05), but not independently. Pulmonary capillary wedge pressures (PCWP) and volume expansion showed no correlation with BNP. In septic shock, increased central venous pressure (CVP) and CVP/PCWP ratio were independently associated with early BNP values (P <0.05).Twenty-eight-day mortality was 47.6% (20 of 42 patients). Daily BNP values poorly predicted outcome; BNP on day 1 > 800 pg/ml (the best cutoff point) fairly predicted mortality, with a sensitivity%, specificity% and area under the curve values of 65, 64 and 0.70, respectively (95% confidence interval = 0.54 to 0.86; P = 0.03). Plasma BNP levels declined faster in survivors than in nonsurvivors in both critical sepsis and septic shock (P ≤0.002). In septic shock, a BNP/CVP ratio >126 pg/mmHg/ml on day 2 and inability to reduce BNP <500 pg/ml implied increased mortality (P ≤0.036).ConclusionsThe severity of critical illness, rather than septic cardiomyopathy, is probably the major determinant of BNP elevation in patients with critical sepsis. Daily BNP values are of limited prognostic value in predicting 28-day mortality; however, fast BNP decline over time and a decrease in BNP <500 pg/ml may imply a favorable outcome.

TheTLNO/TLCOratio in pulmonary function test interpretation

From the authors : We are grateful to C. Borland for his comments on our review of the T LNO/ T LCO ratio (the ratio of the transfer factor of the lung for nitric oxide versus carbon monoxide) [1] and its clinical applications. Undoubtedly, T LNO, on its own, has a role to play in accessing alveolar function in terms of the membrane diffusing capacity, D M. The calculation of pulmonary capillary volume ( Vc ), on the other hand, requires a value for ΘblCO, the specific conductance of blood for carbon monoxide, and there is some doubt about its correct value. The T LNO/ T LCO ratio does not require knowledge …

Cardiovascular Effects of 1 Year of Alagebrium and Endurance Exercise Training in Healthy Older Individuals

Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of irreversible advanced glycation end products. Alagebrium breaks advanced glycation end product crosslinks and improves LV stiffness in aged animals. However, it is unclear whether a strategy of exercise combined with alagebrium would improve LV stiffness in sedentary older humans. Sixty-two healthy subjects were randomized into 4 groups: sedentary+placebo; sedentary+alagebrium (200 mg/d); exercise+placebo; and exercise+alagebrium. Subjects underwent right heart catheterization to define LV pressure-volume curves; secondary functional outcomes included cardiopulmonary exercise testing and arterial compliance. A total of 57 of 62 subjects (67 ± 6 years; 37 f/20 m) completed 1 year of intervention followed by repeat measurements. Pulmonary capillary wedge pressure and LV end-diastolic volume were measured at baseline, during decreased and increased cardiac filling. LV stiffness was assessed by the slope of LV pressure-volume curve. After intervention, LV mass and end-diastolic volume increased and exercise capacity improved (by ≈8%) only in the exercise groups. Neither LV mass nor exercise capacity was affected by alagebrium. Exercise training had little impact on LV stiffness (training × time effect, P=0.46), whereas alagebrium showed a modest improvement in LV stiffness compared with placebo (medication × time effect, P=0.04). Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously sedentary seniors. However, it did show a modestly favorable effect on age-associated LV stiffening. http://www.clinicaltrials.gov. Unique identifier: NCT01014572.

178 Right Ventricle Contractile Reserve and Pulmonary Capillary Volume are the Main Determinants of Aerobic Capacity in Mitral Stenosis

There is a paucity of data regarding consequences of mitral stenosis (MS) on respiratory function and exercise capacity. In view of frequent discrepancies between symptoms and anatomy in MS, identification of determinants of aerobic capacity could be useful in the clinical-decision making process. Our objective was to evaluate the role of cardiac and pulmonary alterations on aerobic capacity in MS. Twenty-eight patients (53±7 y) with history of MS were prospectively included. A comprehensive echocardiography was performed at rest and during exercise. Right ventricular (RV) systolic function was assessed with tricuspid lateral annulus S wave velocity (STric). Respiratory function was assessed at rest with measure of transfer of carbon monoxide (DLCO). We analyzed the two components of DLCO: membrane diffusion (DM) and capillary volume (VCAP). Maximal oxygen uptake (VO2max) was determined during cardio-pulmonary exercise test. Ten patients were examined before (native MS group) and 18 after corrective treatment (treated MS group). The mitral valve functional area (MVA) was 1.3±0.3 cm2 in native MS group and 1.6±0.1 cm2 in treated MS group. Overall, NYHA class was 1.8±0.3, VO2max 18±3 ml/kg/min, maximal workload 85±13 Watts. There were no differences between groups in NYHA class, maximal workload, VO2max, trans-mitral and trans-tricuspid gradients and DLCO. DM and VCAP were impaired in patients with a history of MS. In univariate analysis determinants of VO2max were gender (r=0.6, p=0.001), DM (r=0.65, p=0.04), VCAP (r=0.69, p=0.001), exercise cardiac output (r=0.55, p=0.003), and exercise STric (r=0.56, p=0.008). In multivariate analysis, independent determinants of VO2max were exercice STric (r=0.55, p=0.005) and VCAP (r=0.46, p=0.01). DM and VCAP are impaired in MS. RV contractile reserve and VCAP are the main determinants of aerobic capacity in MS. Theses parameters could be used in the clinical-decision making process in MS.

A systemically administered EP2 receptor agonist stimulates pulmonary angiogenesis in a murine model of emphysema

We investigated whether systemically administered EP2 receptor agonists would stimulate angiogenesis in the emphysematous lungs of mice. Saline or porcine pancreatic elastase was intratracheally administered to C57BL/6J mice to induce the formation of emphysematous lesions, and 4 weeks later the mice were intraperitoneally injected with an EP2 receptor agonist, ONO-AE1-259 or PGE2, or saline on days 1–5 each week for 3 weeks. Intraperitoneal ONO-AE1-259 in the mice in the intratracheal saline group increased pulmonary capillary volume to 114.9% of the control value ( P < 0.05), and when administered to the intratracheal elastase group, ONO-AE1-259 partially restored pulmonary capillary volume, from 70.9% of the control value to 88.3% of the control value ( P < 0.05). Intraperitoneal PGE2 tended to increase pulmonary capillary volume in the mice in the intratracheal saline group ( P = 0.07) but not in the intratracheal elastase group. Intraperitoneal ONO-AE1-259 and PGE2 each increased the concentration of vascular endothelial growth factor (VEGF) and the number of endothelial progenitor cells (EPCs) in circulating blood. These results suggest that systemically administered ONO-AE1-259 stimulates pulmonary angiogenesis in an elastase-induced murine model of emphysema.