Respiratory Gas Exchange Research Articles

Graded and ramp protocols present similar results in apparently healthy subjects

Abstract The aim of the study was to compare maximum oxygen uptake, maximum heart rate, speed corresponding to VO2max, time to exhaustion, and ventilatory thresholds between two maximal test protocols (scaled vs ramp) with equalized metabolic demand in apparently healthy young adults. Twenty-seven subjects of both sexes were analyzed and submitted to two maximum tests: 1) scaled test with 1.2 km∙h-1 every 2 min; 2) ramp test with 0.1 km∙h-1 every 0.18 min; both with 1% slope and maximum total duration of twenty minutes. Respiratory gas exchanges were directly analyzed, and ventilatory thresholds determined through visual inspection. Central tendency and dispersion measures were adopted, as well as paired t-test and effect size. Bland-Altman analysis verified the agreement among variables. Maximum speed showed significance difference (p < 0.01) for the scaled test (14.0 ± 1.9 km∙h-1) and ramp test (14.6 ± 2.3 km∙h-1). Even with small BIAS values, negative trend and high limits of agreement could be observed. Despite the non-difference presented for variables, except for maximum speed, it could be concluded that the scaled test is able to determine the analyzed variables similar to the ramp test, considering the same conditions of the present study.

Changes in respiratory mechanics and gas exchange in robot-assisted radical prostatectomy

Changes in respiratory mechanics and gas exchange in robot-assisted radical prostatectomy

Respiratory System Self-Organization Parameters of an Operator of the System of Continuous Interaction for Decision Making under Complicated Situational Conditions. Research on Mathematical Model

One of the most important tasks for occupational medicine is providing the later development of fatigue and maintaining optimal stability of the functional state of a human operator of continuously interactive systems. A comprehensive study of the oxygen supply of the human body in the process of adaptation to new living conditions and new types of activity allows us to identify the leading links in the cascade of compensatory reactions and evaluate the functional reserves of the organism. Difficulties of a methodological nature that arise when characterizing a human's functional state in the process of his work, lead to the necessity of building mathematical models that describe the functions of basic physiological systems of the organism for the theoretical study of the state of these systems during hard work, assessing the reserve of regulatory mechanisms, predicting possible consequences and correcting the state of the organism. One of these models is a mathematical model of mass transfer and mass exchange of respiratory gases in the human body, which allows simulation of disturbances in the internal and external environment in the dynamics of the respiratory cycle and, thus, predicting possible reactions of the body to these disturbances. The model studied compensatory reactions of the respiratory system during simulation of intense operator activity. The obtained results are evidence of the intensification of this activity, associated with an increase in the rate of oxygen consumption by brain tissues by 10-30%, no doubts that this does not result in significant restructuring of the cardiorespiratory system, more intense activity leads to the active inclusion of the regulation mechanisms of the cardiovascular system and external respiration system, a change in the tone of smooth muscles and is associated with the development of hypoxia. The simulation on a mathematical model of complex situational conditions for the organism of an average human showed that for compensating the load under complex situational conditions, on decision making the decisive role belongs to the performance functional of the control by the hypercapnic stimulus and the change of the ventilation parameters effects stronger on the minimized functional. Determination of the optimum of the human operator and the corresponding changes in the most informative indicators enables the prediction of the boundaries of the zone of optimal working capacity, and in the future, transit to control the functional state of the operator, rise the quality and reliability of the professional selection procedure and conduct a balanced personnel policy for operators of continuously interacting systems.

Prone Ventilation in a 27 Week Pregnant Woman with COVID-19 Severe ARDS

Pregnant women are more sensitive to respiratory pathogens due to the physiological changes related to pregnancy with an increase in morbidity and mortality. Pregnancy and childbirth do not seem to aggravate the course of symptoms of COVID-19 pneumonia. However, reports on optimal management of severe COVID-19-related ARDS during pregnancy are still lacking. To our knowledge only two case reports describe prone ventilation in pregnant women with severe ARDS, no one related to COVID-19. We report the case of a COVID-19 related severe ARDS in a 48-year-old woman in the last trimester of pregnancy. The patient required intensive care hospitalization for 20 days and invasive mechanical ventilation for 15 days. Pronation maneuver during mechanical ventilation relieved hypoxia and prevented mother and fetus damages, thus avoiding an urgent cesarean section and a premature birth. The patient was successfully discharged from the hospital without maternal and fetal sequelae. In our experience prone ventilation can be safely used to improve respiratory gas exchanges in the last trimester of pregnancy in case of severe ARDS.

Ionoregulatory aspects of the hypoxia-induced osmorespiratory compromise in the euryhaline Atlantic killifish (Fundulus heteroclitus): the effects of salinity.

The osmorespiratory compromise is a physiological trade-off between the characteristics of the gill that promote respiratory gas exchange and those that limit passive flux of ions and water with the environment. In hypoxia, changes in gill blood flow patterns and functional surface area that increase gas transfer can promote an exacerbation in ion and water flux. Our goal was to determine whether the osmorespiratory compromise is flexible, depending on environmental salinity (fresh, isosmotic and sea water) and oxygen levels (hypoxia) in euryhaline killifish, Fundulus heteroclitus Plasma ion concentrations were minimally affected by hypoxia, indicating a maintenance of osmoregulatory homeostasis. In freshwater killifish, hypoxia exposure reduced branchial Na+/K+-ATPase and NEM-sensitive ATPase activities, as well as diffusive water flux rates. Unidirectional Na+ influx and Na+ efflux decreased during hypoxia in freshwater, but net Na+ flux remained unchanged. Net loss rates of Cl-, K+ and ammonia were also attenuated in hypoxia, suggesting both transcellular and paracellular reductions in permeability. These reductions appeared to be regulated phenomena as fluxes were restored immediately in normoxia. Na+ flux rates increased during hypoxia in 11 ppt, but decreased in 35 ppt, the latter suggesting a similar response to hypoxia to that in freshwater. In summary, freshwater and seawater killifish experience a reduction in gill permeability, as seen in other hypoxia-tolerant species. Fish acclimated to isosmotic salinity increased Na+ influx and efflux rates, as well as paracellular permeability in hypoxia, responses in accord with the predictions of the classic osmorespiratory compromise.

Can the talk test be used to predict training induced changes in ventilatory threshold?

This study was designed to assess the ability of the Talk Test (TT) to track training-related changes in ventilatory threshold (VT). Thirteen recreational athletes (20.5±1.91 years, males=7) completed two incremental exercise tests (one with respiratory gas exchange and one with the TT) before and after six weeks of self-directed increases in training load. The TT was used to predict VT by assessing the ability to speak comfortably after three-minute exercise stages, based on speech comfort while reciting a 100-word passage. Training load was documented from exercise logs based on session rating of perceived exertion (sRPE) and training duration. Repeated measures ANOVA, with the Tukey’s post-hoc analysis, was used to detect differences between the changes in power output (PO) at the equivocal stage of the Talk Test (EQ) and VT measured by gas exchange (p<.05). Significant mean differences were found between pre- vs. post-training PO and measured VT (116+32.4 vs. 134+32.4 Watts) (p<.05) but not at the EQ stage of the TT (125+40.8 vs. 135+29.8 Watts). The increase in PO at VT (+15.5%) was significantly underestimated by the change in PO at the EQ stage of the TT (+8.0%). The correlation between changes in PO at VT and PO at the EQ stage of the TT was r=0.66, p<.01. However, about 50% of participants did not change their PO at the EQ stage of the TT, so the individual correspondence between TT and measured VT was only moderately strong.

Comparison of two experimental ARDS models in pigs using electrical impedance tomography.

BackgroundAnimal trials contribute to major achievements in medical science. The so-called lavage model is frequently used to evaluate ventilation strategies in acute respiratory distress syndrome (ARDS) using electrical impedance tomography (EIT). But, the lavage model itself might have systematic impacts on EIT parameters. Therefore, we established an additional experimental model, in which ARDS is caused by intravenously administered lipopolysaccharide (LPS). In this study, we want to examine if EIT measurements provide consistent results in both experimental models or whether the pathophysiology of the model influences the findings. Overall, we want to compare both experimental models regarding clinical parameters and EIT-derived indices, namely the global inhomogeneity (GI) index and the regional ventilation delay (RVD) index.MethodsNineteen pigs were included in this study, allocated to the control group (CO; n = 5), lavage group (LAV; n = 7) and LPS group (LPS; n = 7). After baseline measurements and the establishment of ARDS, assessment of respiratory mechanics, hemodynamics, gas exchange and EIT recordings were performed hourly over eight hours.ResultsIn both experimental ARDS models, EIT measurements provided reliable results. But, the GI and the RVD index did not show consistent results as compared to the CO group. Initially, GI and RVD index were higher in the LAV group but not in the LPS group as compared to the CO group. This effect disappeared during the study. Furthermore, the GI index and the RVD index were higher in the LAV group compared to the LPS group in the beginning as well. This, once again, disappeared. Clinical lung injury parameters remained more stable when using LPS.ConclusionThe two models showed quite different influences on the GI and RVD index. This implies, that the underlying pathophysiology affects EIT parameters and thus the findings. Hence, translation to EIT-guided clinical therapy in humans suffering from ARDS might be limited.

Accelerometry calibration in people with class II-III obesity: Energy expenditure prediction and physical activity intensity identification

BackgroundAlmost all accelerometer calibration studies were developed for non-obese people, which hampers an accurate prediction of energy expenditure (EE) and induces a misclassification of sedentary activity (SA) and physical activity intensities (PAI) in class II-III obese people. Research questionThe purpose of this study was to develop regression equations to predict EE and cut-points to classify SA and PAI in severe obese people based on several metrics obtained from hip and back accelerometer placement data. Methods43 class II-III obese participants performed a protocol that included sitting and standing positions and walking at several speeds. During the protocol participants wore an accelerometer at hip and back, and respiratory gas exchange was measured by indirect calorimetry. Accelerometer metrics analyzed were: activity counts, mean amplitude deviation and euclidean norm minus one. EE was predicted through linear mixed models while cut-points to classify SA and PAI were obtained applying receiver operating characteristic curves. Leave-one-out cross-validation data was used to calculate Bland-Altman plots, prediction accuracy, Kappa statistic and percent agreement. ResultsAll prediction models presented a quadratic equation that had as predictors body mass and one of the accelerometer metrics. Predicted EE indicated a good agreement and a root mean square error below 1.02 kcal min−1. Global classification agreement from developed cut-points was categorized as almost perfect with a percent agreement above 84 %. Prediction accuracy and classification agreement were similar among accelerometer metrics in each position and between them in hip and back placement. SignificanceHip and back accelerometer data collected in severe obese people allow to accurately estimate EE and to correctly classify SA and PAI. These results enable future studies to adopt appropriate regression equations and cut-points developed for class II-III obese people rather than those established for non-obese people.

P1800The benefit of atrial septal defect closure in patients with borderline shunt

Abstract Objective Closure of atrial septal defect in patients with borderline shunt is controversial. The aim of the study was to evaluate the outcomes of transcatheter closure of secundum atrial septal defect (ASD) in the patients with the borderline shunt. Methods 215 pts (126 F,89 M) with a mean age of 31.9±18.2 (16–58) years with a small ASD who underwent transcatheter closure were analyzed. All patients had an isolated secundum ASD with pulmonary to systemic blood flow Qp:Qs ratio≤1.5, mean 1.2±0.6 (1.1–1.5). A symptom-limited treadmill exercise test with respiratory gas exchange analysis, transthoracic color Doppler echocardiographic study and Quality of life (QoL) (using the SF36 questionnaire (SF36q)) were repeated in all pts before and 36 months after the procedure. Results The device was successfully implanted in all pts (procedure time 19.1±5.2 (8–38) minutes, fluoroscopy time 8.1±4.4 (6–13) minutes). There were no major complications. The defect echo diameter was 7.7±3.9 (5 - 15) mm. The diameter of the implanted devices ranged from 6 to 18 mm. After 36 months of ASD closure, all the pts showed a significant improvement of exercise capacity. 7 QoL parameters (except mental health) improved at 36 months of follow-up compared with baseline. The mean SF36q scale increased in 168 (78.1%) pts of mean 40.2±20.1 (9–72). The right ventricular dimension decreased in 173 pts (80.4%) (Table 1). Table 1 Parameter Before ASD closure 36 months after ASD closure p value Time of exercise (min) 12.1±5.2 18.6±4.3 <0.001 VO2 peak (ml/kg/min) 10.2±4.7 14.8±4.2 <0.001 SF36q scale 0–100 37.3±22.3 79±29.5 <0.001 Right atrial area (cm2) 20.1±1.7 14.7±1.5 <0.001 Right ventricular area (cm2) 18.1±1.4 12.2±1.5 <0.001 Conclusions ASD closure in patients with borderline shunt resulted in a significant and long-term clinical and hemodynamic improvement after percutaneous treatment.

Challenges and perspectives in porcine model of acute lung injury using oleic acid

The oleic acid (OA) models of lung injury try to simulate the findings of human Acute Respiratory Distress Syndrome (ARDS). However, these models are difficult to replicate because they vary in terms of animals species, OA doses, time for establishment of lung injury, different observation periods and settings of mechanical ventilation. The objective of this study was to evaluate a protocol of administration of OA in lung injury model, challenges in its development and its effects on respiratory mechanics, hemodynamic changes, histology, gas exchange and mortality. We then submitted ten Large White pigs to acute lung injury through intravenous infusion of acid oleic in the pulmonary artery. The mortality of the model was 50%, due to an intense hemodynamic instability during OA administration, even with early use of vasoactive drugs. Three animals required additional doses of OA to achieve criteria for acute lung injury. Histology showed findings consistent with acute lung injury. However, more pulmonary edema was observed in lower segments than in upper segments of both lungs (p = 0.01). IL-6 and IL-8 were significantly increased compared to normal lungs (p < 0.05), and IL-6 showed higher levels in upper segments compared to lower segments (p = 0.03). Positive cells for Caspase 3 were present in all samples, localized mainly in respiratory epithelial cells and macrophages. In conclusion, this model shows histological findings of acute lung injury and inflammatory response similar to those of clinical ARDS, it presents high mortality, inconsistent reproducibility and hardly controlled hemodynamic instability.

The effect of Betanin parenteral pretreatment on Jejunal and pulmonary tissue histological architecture and inflammatory response after Jejunal ischemia-reperfusion injury

Intestinal ischemic-reperfusion (IR) injury has detrimental effects on both local and distant organs in the body. Betanin is known for its antioxidant properties, and it is found mostly in vegetables. Therefore, the aim of the present study was to test the hypothesis that betanin administration prior intestinal IR, may be beneficial in protecting jejunal mucosa and lung parenchyma against IR damage. Male specific pathogen-free Charles River Wistar rats were used (n = 42). Betanin (50 mg/kg) was administered intraperitoneally 30 min before ischemia of the superior mesenteric artery lasting 1 h, followed by 1, 4 and 24 h of reperfusion. Immunohistochemical as well as histomorphometrical analysis indicated a protective effect of betanin pretreatment on jejunal tissue. Regarding morphometrical analysis betanin significantly (p < 0.01) augments intestinal villus height after 24 of reperfusion comparing to early stages. Betanin application reduced number of mast cells population in early reperfusion periods (p < 0.05). The protective effect of betanin on lung parenchyma, was detected in late reperfusion period (24 h) with improvement of histopathological injury index and morphometric analysis (p < 0.001 for both). The improvement of histopathological injury index (p < 0.001) and morphometric analysis (p < 0.001) during the late reperfusion period, suggests a protective effect of betanin on lung parenchyma. Moreover, suppression of the inflammatory response was mirrored by the reduction of myeloperoxidase (MPO) positive cells within lung parenchyma after 1 and 4 h of reperfusion (p < 0.001). Especially, during the first 4 h of reperfusion after betanin administration, a reduction of 74% of the polymorphonuclear neutrophils infiltration (MPO positive cell population) and of a nearly 46% of active MCs was observed. Upon morphometric examination, the lung histological architecture after 24 h of reperfusion appeared to be almost 100% better following betanin treatment, with 25% thinner interalveolar septa and 20% larger alveolar surface for respiratory gas exchange. The results suggest that betanin pretreatment protects the jejunal mucosa and the lung parenchyma, as well as reduces the inflammatory cell density after intestinal IR injury.

Exercise chronotropic incompetence phenotypes the level of cardiovascular risk and exercise gas exchange impairment in the general population. An analysis of the Euro-EX prevention trial.

Chronotropic insufficiency (CI) is defined as the inability of the heart to increase its rate commensurate with increased demand. Exercise CI is an established predictor of major adverse cardiovascular events in patients with cardiovascular diseases. The aim of this study was to evaluate how exercise CI phenotypes different levels of cardiovascular risk and how it may better perform in defining cardiovascular risk when analysed in the context of cardiopulmonary exercise test (CPET)-derived measures and standard echocardiography in a healthy population with variable cardiovascular risk profile. Apparently healthy individuals (N = 702, 53.8% females) with at least one major cardiovascular risk factor (MCVRF; hypertension, diabetes, tabagism, dyslipidaemia, body mass index > 25), enrolled in the Euro-EX prevention trial, underwent CPET. CI was defined as the inability to reach 80% of the chronotropic index, that is, the ratio of peak heart rate - rest heart rate/peak heart rate - age predicted maximal heart rate (AMPHR: 220 - age), they were divided into four groups according to the heart rate reserve (<80%>) and respiratory gas exchange ratio (RER; < 1.05>) as a marker of achieved maximal performance. Subjects with a RER < 1.05 (n = 103) were excluded and the final population (n = 599) was divided into CI group (n = 472) and no-CI group (n = 177). Compared with no-CI, CI subjects were more frequently females with a history of hypertension in a high rate. CI subjects also exhibited a significantly lower peak oxygen uptake (VO2) and circulatory power and an echocardiographic pattern indicative of higher left atrial volume index and left ventricular mass index. An inverse stepwise relationship between heart rate reserve and number of MCVRFs was observed (one MCVRF: 0.71 ± 0.23; two MCVRFs: 0.68 ± 0.24, three MCVRFs: 0.64 ± 0.20; four MCVRFs: 0.64 ± 0.23; five MCVRFs: 0.57 ± 18; p < 0.01). In multivariate analysis the only variable found predicting CI was peak VO2 (p < 0.05; odds ratio 0.91; confidence interval 0.85-0.97). In a population of apparently healthy subjects, exercise CI is common and phenotypes the progressive level of cardiovascular risk by a tight relationship with MCVRFs. CI patients exhibit some peculiar abnormal exercise gas exchange patterns (lower peak VO2 and exercise oscillatory ventilation) and echo-derived measures (higher left atrium size and left ventricle mass) that may well anticipate evolution toward heart failure.

COMPROMISE SOLUTION OF CONFLICT SITUATIONS IN THE PROBLEM OF OPTIMAL CONTROL IN DECISION MAKING UNDER THE COMPLEX SITUATIONAL CONDITIONS

One of the most important directions of the research in medicine of labor is the development of methodology and methods for the estimation and predicting of the functional reserves of organisms of decision-makers, whose professional activity takes place under the extreme conditions, in particular, with the joint action of hypoxic hypoxia and conditions of complex situational stress. In present article it was proposed to apply mathematical model of the functional system of respiration for the simulation conflict-controlled processes that appear during the self-organization of respiratory system under the conditions of complex situational stress in process of decisions’ making. The mathematical model of mass transfer and mass exchange of respiratory gases in human organism is represented as a system of ordinary differential equations, which in the dynamics of the respiratory cycle describe the changes in the stresses of oxygen and carbon dioxide at all stages of its path in human organism. The solution of this problem, taking into account both intra- systemic as well as inter systemic mechanisms, allows to predict the optimal values of active control parameters - ventilation, volume velocities of systemic and organ blood circuits. The results of numerical experiments were presented. Their purpose was to study the behavior of quality control functional for hypoxic and hypercapnic regulation stimuli in difficult situational conditions during decision making and to find optimal control parameters when seeking a compromise solution of conflict situation that appear between control elements and executive elements of self-regulation. Numerical simulation has demonstrated that during the load compensation in difficult situational conditions, during decision making the key role belongs to quality control functional of the hypercapnic stimulus and to behavior of quality functional, which is minimized; the change in the parameters of ventilation influences greatly. The optimum control influences were determined at the simulation of load compensation on the brain tissues for averaged person. Further developments can turn this model into a rather simple and reliable research tool and have both theoretical and practical value.

Mechanical Ventilation Guided by Electrical Impedance Tomography in Children With Acute Lung Injury.

To provide proof-of-concept for a protocol applying a strategy of personalized mechanical ventilation in children with acute respiratory distress syndrome. Positive end-expiratory pressure and inspiratory pressure settings were optimized using real-time electrical impedance tomography aiming to maximize lung recruitment while minimizing lung overdistension. Prospective interventional trial. Two PICUs. Eight children with early acute respiratory distress syndrome (< 72 hr). On 3 consecutive days, electrical impedance tomography-guided positive end-expiratory pressure titration was performed by using regional compliance analysis. The Acute Respiratory Distress Network high/low positive end-expiratory pressure tables were used as patient's safety guardrails. Driving pressure was maintained constant. Algorithm includes the following: 1) recruitment of atelectasis: increasing positive end-expiratory pressure in steps of 4 mbar; 2) reduction of overdistension: decreasing positive end-expiratory pressure in steps of 2 mbar until electrical impedance tomography shows collapse; and 3) maintaining current positive end-expiratory pressure and check regional compliance every hour. In case of derecruitment start at step 1. Lung areas classified by electrical impedance tomography as collapsed or overdistended were changed on average by -9.1% (95% CI, -13.7 to -4.4; p < 0.001) during titration. Collapse was changed by -9.9% (95% CI, -15.3 to -4.5; p < 0.001), while overdistension did not increase significantly (0.8%; 95% CI, -2.9 to 4.5; p = 0.650). A mean increase of the positive end-expiratory pressure level (1.4 mbar; 95% CI, 0.6-2.2; p = 0.008) occurred after titration. Global respiratory system compliance and gas exchange improved (global respiratory system compliance: 1.3 mL/mbar, 95% CI [-0.3 to 3.0], p = 0.026; Pao2: 17.6 mm Hg, 95% CI [7.8-27.5], p = 0.0039; and Pao2/Fio2 ratio: 55.2 mm Hg, 95% CI [27.3-83.2], p < 0.001, all values are change in pre vs post). Electrical impedance tomography-guided positive end-expiratory pressure titration reduced regional lung collapse without significant increase of overdistension, while improving global compliance and gas exchange in children with acute respiratory distress syndrome.

Response.

Dear Editor-in-Chief, We are grateful for the opportunity to respond to the insightful critiques provided by our colleagues and clarify our study’s rationale (1). Load carriage over complex terrain is a common scenario for dismounted military. However, it is challenging to study as it involves prolonged outdoor walking at a varying pace over a series of route segments of different distances, grades, and surfaces. Global positioning systems (GPS) offer a practical solution for obtaining data that can be input into walking equations to estimate energy expenditure (EE). We made estimates of EE using GPS-based modeling as a pragmatic means of providing needed solutions to our military customers for use in real-world, non–steady-state activities. Our study attempted to estimate EE contributed by aerobic metabolism in dynamic field conditions. When taken in the context of exercise with a discrete on and off phase, we see how our methodology has led to some confusion. Because of respiratory gas exchange kinetics, measures obtained in real time via gas exchange display a classic half-time response, both on and off; therefore, they do not directly compare with steady-state estimates. The approach we took sought to adjust for this half-time response. As part of our rationale, we included references describing delayed respiratory gas exchange kinetics (2,3) and excess postexercise oxygen consumption (EPOC) (4,5). Typically, estimates of EE are made using a square-wave prediction; however, using this approach avoids accounting for these half-time responses. To address these time offsets, we applied a simple exponential smoothing filter to better align walking equation estimates with aerobic EE calculated from measured oxygen uptake. This approach assumes the steady-state energy cost for a given work is correct but adjusts the time period during which the cost is expended to closer approximate how the energy cost is met by aerobic metabolism. For example, exponential smoothing a basic on–off square-wave results in a curve similar to the oxygen deficit/EPOC response to exercise. As with any method, there are limitations and room for improvement. On one hand, exponential smoothing does not immediately account for the contribution of all anaerobic energy stores when walking speed, grade, or terrain costs increase. On the other hand, instantaneous EE estimates are difficult to verify, and solely using them ignores order effects such as additional aerobic EE during trail segments that follow more metabolically taxing ones (e.g., downhill slope after a climb to the summit). To address other raised concerns in order: (i) GPS device details were listed in the original manuscript; (ii) we did state the need for downhill correction factor(s) but do note our colleagues have since developed a series of equations estimating EE during level, uphill, and downhill walking from GPS, heart rate, and accelerometry (6); (iii) the same conversion factor was applied to both measured and estimated V˙O2; and (iv) our colleagues’ equation estimates V˙O2 from combined mass of the individual plus all equipment. We appreciate the constructive feedback and look forward to future work in this area. Adam W. Potter David P. Looney William R. Santee U.S. Army Research Institute of Environmental MedicineNatick, MA

Variable Ventilation Is Equally Effective as Conventional Pressure Control Ventilation for Optimizing Lung Function in a Rabbit Model of ARDS.

BackgroundIntroducing mathematically derived variability (MVV) into the otherwise monotonous conventional mechanical ventilation has been suggested to improve lung recruitment and gas exchange. Although the application of a ventilation pattern based on variations in physiological breathing (PVV) is beneficial for healthy lungs, its value in the presence of acute respiratory distress syndrome (ARDS) has not been characterized. We therefore aimed at comparing conventional pressure-controlled ventilation with (PCS) or without regular sighs (PCV) to MVV and PVV at two levels of positive end-expiratory pressure (PEEP) in a model of severe ARDS.MethodsAnesthetised rabbits (n = 54) were mechanically ventilated and severe ARDS (PaO2/FiO2 ≤ 150 mmHg) was induced by combining whole lung lavage, i.v. endotoxin and injurious ventilation. Rabbits were then randomly assigned to be ventilated with PVV, MVV, PCV, or PCS for 5 h while maintaining either 6 or 9 cmH2O PEEP. Ventilation parameters, blood gas indices and respiratory mechanics (tissue damping, G, and elastance, H) were recorded hourly. Serum cytokine levels were assessed with ELISA and lung histology was analyzed.ResultsAlthough no progression of lung injury was observed after 5 h of ventilation at PEEP 6 cmH2O with PVV and PCV, values for G (58.8 ± 71.1[half-width of 95% CI]% and 40.8 ± 39.0%, respectively), H (54.5 ± 57.2%, 50.7 ± 28.3%), partial pressure of carbon-dioxide (PaCO2, 43.9 ± 23.8%, 46.2 ± 35.4%) and pH (−4.6 ± 3.3%, −4.6 ± 2.2%) worsened with PCS and MVV. Regardless of ventilation pattern, application of a higher PEEP improved lung function and precluded progression of lung injury and inflammation. Histology lung injury scores were elevated in all groups with no difference between groups at either PEEP level.ConclusionAt moderate PEEP, variable ventilation based on a pre-recorded physiological breathing pattern protected against progression of lung injury equally to the conventional pressure-controlled mode, whereas mathematical variability or application of regular sighs caused worsening in lung mechanics. This outcome may be related to the excessive increases in peak inspiratory pressure with the latter ventilation modes. However, a greater benefit on respiratory mechanics and gas exchange could be obtained by elevating PEEP, compared to the ventilation mode in severe ARDS.

Exercise training intensity determination in cardiovascular rehabilitation: Should the guidelines be reconsidered?

In the rehabilitation of cardiovascular disease patients a correct determination of the endurance-type exercise intensity is important to generate health benefits and preserve medical safety. It remains to be assessed whether the guideline-based exercise intensity domains are internally consistent and agree with physiological responses to exercise in cardiovascular disease patients. A total of 272 cardiovascular disease patients without pacemaker executed a maximal cardiopulmonary exercise test on bike (peak respiratory gas exchange ratio >1.09), to assess peak heart rate (HRpeak), oxygen uptake (VO2peak) and cycling power output (Wpeak). The first and second ventilatory threshold (VT1 and VT2, respectively) was determined and extrapolated to %VO2peak, %HRpeak, %heart rate reserve (%HRR) and %Wpeak for comparison with guideline-based exercise intensity domains. VT1 was noted at 62 ± 10% VO2peak, 75 ± 10% HRpeak, 42 ± 14% HRR and 47 ± 11% Wpeak, corresponding to the high intensity exercise domain (for %VO2peak and %HRpeak) or low intensity exercise domain (for %Wpeak and %HRR). VT2 was noted at 84 ± 9% VO2peak, 88 ± 8% HRpeak, 74 ± 15% HRR and 76 ± 11% Wpeak, corresponding to the high intensity exercise domain (for %HRR and %Wpeak) or very hard exercise domain (for %HRpeak and %VO2peak). At best (when using %Wpeak) in only 63% and 72% of all patients VT1 and VT2, respectively, corresponded to the same guideline-based exercise intensity domain, but this dropped to about 48% and 52% at worst (when using %HRR and %HRpeak, respectively). In particular, the patient's VO2peak related to differently elicited guideline-based exercise intensity domains (P < 0.05). The guideline-based exercise intensity domains for cardiovascular disease patients seem inconsistent, thus reiterating the need for adjustment.

Cardiorespiratory fitness is not associated with risk of venous thromboembolism: a cohort study

Objectives. The inverse and independent association between cardiorespiratory fitness (CRF) and arterial thrombotic disease is well established. However, the potential association between CRF and venous thromboembolism (VTE) is not well known. We aimed to assess the prospective association of CRF with the risk of VTE. Design. Cardiorespiratory fitness, as measured by maximal oxygen uptake (VO2max), was assessed using a respiratory gas exchange analyser in 2,249 men aged 42–61 years without a history of VTE at baseline in the Kuopio Ischemic Heart Disease prospective cohort. Cox-regression models were used to calculate hazard ratios (HR) with 95% confidence interval (CI) for VTE. We corrected for within-person variability in CRF levels using data from repeat measurements taken several years apart. Results. There were 144 (6.4%) incident VTE events recorded during a median follow-up of 25.2 years. The age-adjusted regression dilution ratio of CRF was 0.58 (95% CI: 0.53–0.64). The risk of VTE did not significantly decrease per 1 standard deviation increase in CRF in age-adjusted analysis (HR 0.90; 95% CI 0.75–1.08). The association remained consistent in analyses adjusted for several established and emerging risk factors (HR 0.90; 95% CI 0.73–1.12). The corresponding adjusted HRs were 0.80 (95% CI: 0.52–1.23) and 0.82 (95% CI: 0.51–1.32) respectively, when comparing the extreme tertiles of CRF levels. Conclusions. In a middle-aged Caucasian male population, CRF was not associated with future risk of VTE. Further studies are required to confirm and to generalize these findings, particulary in women and other age groups.

Cellular crosstalk in the development and regeneration of the respiratory system.

The respiratory system, including the peripheral lungs, large airways and trachea, is one of the most recently evolved adaptations to terrestrial life. To support the exchange of respiratory gases, the respiratory system is interconnected with the cardiovascular system, and this interconnective nature requires a complex interplay between a myriad of cell types. Until recently, this complexity has hampered our understanding of how the respiratory system develops and responds to postnatal injury to maintain homeostasis. The advent of new single-cell sequencing technologies, developments in cellular and tissue imaging and advances in cell lineage tracing have begun to fill this gap. The view that emerges from these studies is that cellular and functional heterogeneity of the respiratory system is even greater than expected and also highly adaptive. In this Review, we explore the cellular crosstalk that coordinates the development and regeneration of the respiratory system. We discuss both the classic cell and developmental biology studies and recent single-cell analysis to provide an integrated understanding of the cellular niches that control how the respiratory system develops, interacts with the external environment and responds to injury.

MitraClip improves cardiopulmonary exercise test in patients with systolic heart failure and functional mitral regurgitation

AimsThe aim of this study is to evaluate changes in cardiopulmonary exercise test (CPET) after percutaneous mitral valve repair (PMVR) with MitraClip in patients with heart failure with reduced ejection fraction who are potentially candidates for heart transplantation or destination left ventricular assist device.Methods and resultsProspective registry of all consecutive patients with heart failure with reduced ejection fraction and functional mitral regurgitation (MR) underwent elective PMVR between October 2015 and March 2018 in our institution. Patients with preserved or mid‐range left ventricular ejection fraction (>40%), advanced age (>75 years old), or severe co‐morbidities (end‐stage organ damage) were not included. Treadmill exercise testing with respiratory gas exchange analysis was carried out in 11 patients (male, 72.7%; median age, 67 years old) within the month prior to the procedure and at 6 month follow‐up. PMVR was successfully performed in all patients. At 6 month follow‐up, PMVR was associated with an improvement in New York Heart Association functional class (P = 0.021) and a reduction in MR severity (P = 0.013) and N‐terminal pro‐brain natriuretic peptide levels (2805 [1878–5022] vs. 1485 [654–3032] pg/mL; P = 0.012). All patients completed pre‐procedural and post‐procedural CPET, and all the studies showed a respiratory exchange ratio ≥1 and were consistent with sufficient exercise effort. Compared with pre‐procedural CPET, patients showed a significant increase in exercise time (295 [110–335] vs. 405 [261–540] s; P = 0.047), VO2 (9.8 [9.1–13.4] vs. 13.5 [12.1–16.8] mL/kg/min; P = 0.033), ventilatory anaerobic threshold (510 [430–950] vs. 850 [670–1070] mL/kg/min; P = 0.033), peak O2 pulse (7.2 [4.3–8.6] vs. 8.3 [6.2–11.8] mL/beat; P = 0.033), and workload (5 [3–6] vs. 6 [5–8] metabolic equivalents; P = 0.049).ConclusionsPercutaneous mitral valve repair with MitraClip was associated with an enhancement in cardiopulmonary performance in patients with systolic heart failure and secondary MR.