Impaired Pulmonary Gas Exchange Research Articles

Respiratory and cardiopulmonary limitations to aerobic exercise capacity in adults born preterm.

Adults born preterm, regardless of whether they develop bronchopulmonary dysplasia, have underdeveloped respiratory and cardiopulmonary systems. The resulting impaired respiratory and cardiopulmonary systems are inadequate for the challenges imposed by aerobic exercise, which is exacerbated by the presence of bronchopulmonary dysplasia. Thus the respiratory and cardiopulmonary systems of these preterm individuals may be the most influential contributors to the significantly lower aerobic exercise capacity compared with their term born counterparts. The precise underlying cause(s) of the lower aerobic exercise capacity in adults born preterm is not entirely known but could be a number of interrelated parameters including mechanical ventilatory constraints, impaired pulmonary gas exchange efficiency, and excessive cardiopulmonary pressures. Likewise, additional aspects, such as impaired cardiovascular function and altered muscle bioenergetics, may play additional roles in limiting aerobic exercise capacity. Whether or not all or some of these aspects are present in adults born preterm and precisely how they may contribute to the lower aerobic exercise capacity are only beginning to be systematically explored. The purpose of this mini-review is to outline what is currently known about the respiratory and cardiopulmonary limitations during exercise in this population and to identify key areas where additional knowledge will help to advance this area. Additionally, where possible, we highlight the similarities and differences between obstructive lung disease resulting from preterm birth and chronic obstructive pulmonary disease (COPD) as the physiology and pathophysiology of these two forms of obstructive lung disease may not be identical.

Individualised positive end-expiratory pressure guided by electrical impedance tomography for robot-assisted laparoscopic radical prostatectomy: a prospective, randomised controlled clinical trial

BackgroundRobot-assisted laparoscopic radical prostatectomy requires general anaesthesia, extreme Trendelenburg positioning and capnoperitoneum. Together these promote impaired pulmonary gas exchange caused by atelectasis and may contribute to postoperative pulmonary complications. In morbidly obese patients, a recruitment manoeuvre (RM) followed by individualised PEEP improves intraoperative oxygenation and end-expiratory lung volume (EELV). We hypothesised that individualised PEEP with initial RM similarly improves intraoperative oxygenation and EELV in non-obese individuals undergoing robot-assisted prostatectomy. MethodsForty males (age, 49–76 yr; BMI <30 kg m−2) undergoing prostatectomy received volume-controlled ventilation (tidal volume 8 ml kg−1 predicted body weight). Participants were randomised to either (1) RM followed by individualised PEEP (RM/PEEPIND) optimised using electrical impedance tomography or (2) no RM with 5 cm H2O PEEP. The primary outcome was the ratio of arterial oxygen partial pressure to fractional inspired oxygen (Pao2/Fio2) before the last RM before extubation. Secondary outcomes included regional ventilation distribution and EELV which were measured before, during, and after anaesthesia. The cardiovascular effects of RM/PEEPIND were also assessed. ResultsIn 20 males randomised to RM/PEEPIND, the median PEEPIND was 14 cm H2O [inter-quartile range, 8–20]. The Pao2/Fio2 was 10.0 kPa higher with RM/PEEPIND before extubation (95% confidence interval [CI], 2.6–17.3 kPa; P=0.001). RM/PEEPIND increased end-expiratory lung volume by 1.49 L (95% CI, 1.09–1.89 L; P<0.001). RM/PEEPIND also improved the regional ventilation of dependent lung regions. Vasopressor and fluid therapy was similar between groups, although 13 patients randomised to RM/PEEPIND required pharmacological therapy for bradycardia. ConclusionIn non-obese males, an individualised ventilation strategy improved intraoperative oxygenation, which was associated with higher end-expiratory lung volumes during robot-assisted laparoscopic prostatectomy. Clinical trial registrationDRKS00004199 (German clinical trials registry)

Impaired pulmonary gas exchange efficiency, but normal pulmonary artery pressure increases, with hypoxia in men and women with a patent foramen ovale.

What is the central question of this study? Do individuals with a patent foramen ovale (PFO+ ) have a larger alveolar-to-arterial difference in ( ) than those without (PFO- ) and/or an exaggerated increase in pulmonary artery systolic pressure (PASP) in response to hypoxia? What is the main finding and its importance? PFO+ had a greater while breathing air, 16% and 14% O2 , but not 12% or 10% O2 . PASP increased equally in hypoxia between PFO+ and PFO- . These data suggest that PFO+ may not have an exaggerated acute increase in PASP in response to hypoxia. Patent foramen ovale (PFO) is present in 30-40% of the population and is a potential source of right-to-left shunt. Accordingly, those with a PFO (PFO+ ) may have a larger alveolar-to-arterial difference in ( ) than those without (PFO- ) in normoxia and with mild hypoxia. Likewise, PFO is associated with high-altitude pulmonary oedema, a condition known to have an exaggerated pulmonary pressure response to hypoxia. Thus, PFO+ may also have exaggerated pulmonary pressure increases in response to hypoxia. Therefore, the purposes of the present study were to systematically determine whether or not: (1) the was greater in PFO+ than in PFO- in normoxia and mild to severe hypoxia and (2) the increase in pulmonary artery systolic pressure (PASP) in response to hypoxia was greater in PFO+ than in PFO- . We measured arterial blood gases and PASP via ultrasound in healthy PFO+ (n=15) and PFO- (n=15) humans breathing air and 30min after breathing four levels of hypoxia (16%, 14%, 12%, 10% O2 , randomized and balanced order) at rest. The was significantly greater in PFO+ compared to PFO- while breathing air (2.1±0.7vs. 0.4±0.3Torr), 16% O2 (1.8±1.2vs. 0.7±0.8Torr) and 14% O2 (2.3±1.2vs. 0.7±0.6Torr), but not 12% or 10% O2 . We found no effect of PFO on PASP at any level of hypoxia. We conclude that PFO influences pulmonary gas exchange efficiency with mild hypoxia, but not the acute increase in PASP in response to hypoxia.

COVID-19 and the pulmonary vasculature.

COVID-19 and the pulmonary vasculature.

Organizing Pneumonia and COVID-19

BACKGROUND: Potential sequelae of coronavirus disease 2019 (COVID-19) are still largely unknown. Here, we report, for the first time to our knowledge, the occurrence of an organizing pneumonia-like disease (OPLD) in patients with COVID-19 during hospital admission. METHODS: Observational, uncontrolled series of 53 patients hospitalized in our institution because of COVID-19 pneumonia (March-April 2020). Patients were referred to us by their attending physician because of computed tomography (CT) findings. The demographics, clinical, imaging and biological characteristics of these patients were obtained from their electronic medical records. FINDINGS: Mean age was 63±11 years, most patients were males (74%) and only a few (4%) were current smokers. As previously reported in COVID-19, on admission C-reactive protein (CRP), ferritin and D-Dimer levels were elevated. Pulmonary gas exchange was moderately impaired in most patients and chest X-ray mostly showed bilateral pulmonary opacities. Because persistence/worsening of radiological images and/or deterioration of pulmonary gas exchange, attending physicians ordered a CT scan that showed different degrees of groundglass opacities with peripheral, linear and perilobular consolidations, with reverse halo appearance, associated with bronchial dilatation and architectural distortion in all patients, compatible with organizing pneumonia. At CT time (10±5 days after admission), CRP levels were significantly lower and D-Dimer higher, than those determined on hospital admission. Most patients respond to systemic steroid treatment. INTERPRETATION: Patients with COVID-19 can develop an OPLD during hospitalization. Its long-term outcome remains to be determined. FUNDING STATEMENT: JS was partially supported by the Department of Health of Generalitat de Catalunya (SLT008/18/00176), in the call for grants 2019-2021, under a competitive regime, for the financing of different programs and instrumental actions included in the Strategic Research and Innovation Plan in Health 2016-2020. DECLARATION OF INTERESTS: Dr. Agusti reports grants and personal fees from GSK, Menarini, AstraZeneca and personal fees from Chiesi, outside the submitted work; Dr. Sellares reports grants and personal fees from Boehringer and Roche, personal fees from GSK, Chiesi and Gebro, outside the submitted work; R. Faner reports grants from GSK, grants from Menarini, outside the submitted work; the rest of authors have nothing to disclose. ETHICS APPROVAL STATEMENT: The Institutional Ethics Board of Hospital Clinic of Barcelona, Spain, approved this study and, due to the nature of retrospective chart review, waived the need for informed consent from individual patients (Comite Etic d´Investigacio Clinica; HCB/2020/0422).

Exercise intolerance in heart failure: The important role of pulmonary hypertension

What is the topic of this review? This review concerns the negative impact of pulmonary hypertension (PH) on the pulmonary haemodynamic and gas exchange responses to exercise, considering the mechanisms by which PH plays a role in exercise intolerance in heart failure (HF) patients. What advances does it highlight? The hallmark limited pulmonary vascular 'reserve' and impaired pulmonary gas exchange responses to exercise in HF are worsened by the development of PH; these are key determinants of exercise intolerance. Even HF patients who present with 'normal' pulmonary vascular function experience exercise-induced PH, which plays a role in exercise intolerance. Patients with heart failure universally complain of exertional intolerance, but the underlying cause(s) of this intolerance may differ between patients with different disease phenotypes. Exercise introduces an impressive stress to the lungs, where elevations in venous return and cardiac output engender substantial increases in pulmonary blood volume and flow. Relative to healthy individuals, the pulmonary vascular reserve to accept this increase in pulmonary perfusion is compromised in heart failure, with a growing body of evidence suggesting that the development of pulmonary hypertension (PH), and in particular a precapillary component of PH, worsens the pulmonary haemodynamic response to exercise in these patients. Characterized by an exaggerated increase in pulmonary arterial pressure and an elevation in pulmonary vascular resistance, this dysfunctional pulmonary haemodynamic response plays a role in exercise intolerance, probably through an impairment of right ventricular function, underperfusion of the pulmonary circulation and a subsequent reduction in systemic blood flow and oxygen delivery. The hallmark abnormalities in ventilatory and pulmonary gas exchange that accompany heart failure, including a greater ventilatory equivalent for carbon dioxide, are also worsened by the development of PH. This raises the possibility that measures of exercise pulmonary gas exchange might help to 'describe' underlying PH in heart failure; however, several fundamental issues and questions need to be addressed before such gas exchange measures could truly be considered efficacious measures used to differentiate the type of PH and track the severity of PH in heart failure. exercise intolerance, heart failure, pulmonary gas exchange, pulmonary haemodynamics, pulmonary hypertension.

Coronavirus infections and immune responses.

Coronaviruses (CoVs) are by far the largest group of known positive‐sense RNA viruses having an extensive range of natural hosts. In the past few decades, newly evolved Coronaviruses have posed a global threat to public health. The immune response is essential to control and eliminate CoV infections, however, maladjusted immune responses may result in immunopathology and impaired pulmonary gas exchange. Gaining a deeper understanding of the interaction between Coronaviruses and the innate immune systems of the hosts may shed light on the development and persistence of inflammation in the lungs and hopefully can reduce the risk of lung inflammation caused by CoVs. In this review, we provide an update on CoV infections and relevant diseases, particularly the host defense against CoV‐induced inflammation of lung tissue, as well as the role of the innate immune system in the pathogenesis and clinical treatment.

Hemodynamic monitoring of ARDS by critical care echocardiography

Acute respiratory distress syndrome (ARDS) is a major cause of morbidity and mortality in intensive care units and affects about 10% of critically ill patients and almost 25% of mechanically ventilated patients. It is characterized by life-threatening impairment of pulmonary gas exchange, but in two-thirds of cases is associated with hemodynamic instability. Shock is the primary factor influencing mortality and is driven by sepsis in half of the cases and by a more specific mechanism of ARDS in the other half, which is pulmonary vascular dysfunction, i.e., pulmonary hypertension related to the inflammatory process in the lung, which is very sensitive to a respiratory strategy. ARDS-related right ventricular failure, which is also named acute cor pulmonale (ACP), occurs in 20–25% of patients in the area of lung protective ventilation. In this condition, critical care echocardiography (CCE) plays a central role in adequate hemodynamic assessment and management at the bedside because of its ability to yield information quickly on cardiac dimensions and function, respiratory variations of vena cava dimensions and changes in cardiac output in response to therapy. Added to clinical and laboratory data, with invasive blood pressure monitoring and a central venous catheter, such information can be used to define the cause of circulatory failure, to evaluate the benefit and risk balance of fluid expansion, and to consider a strategy for right ventricle protection. Moreover, in the most severe situations, CCE can also guide the establishment and good functioning of extracorporeal membrane oxygenation (ECMO). In this article, we illustrate and summarize the value of CCE in ARDS and give some physiological pointers to its appropriate use.

Non‐Invasive Pulmonary Gas Exchange Measurements Following Deep Breath‐Hold Diving

Breath‐hold diving is a ubiquitous activity, with recreational, fishing, military and competitive divers. During a dive, immersion and the increasing hydrostatic pressure of descent facilitate cardiovascular adjustments that promote a blood volume shift into the heart and chest vasculature, further augmenting autonomic responses (i.e. diving bradycardia, peripheral vasoconstriction, and splenic contraction) to conserve O2. Exceeding the compliant capacity of the lung and associated tissues can result in pulmonary injury called squeeze, which is characterized by post‐dive coughing, wheezing and hemoptysis. To provide insight into the consequences of such lung squeeze, our objective was to evaluate the time‐course of a maximal deep dive on pulmonary gas exchange, pulmonary artery systolic pressures (PASP), and ultrasound lung comets (ULCs). Ten healthy trained breath‐hold divers (33±9 yr; 80±15 kg; 185±9 cm) performed a maximal effort dive (55±12 m; range 40–76 m). Pulmonary gas exchange and PASP were performed at baseline, and repeated at 10 and 60 min post dive. Pulmonary gas exchange was non‐invasively measured by collecting end‐tidal PO2 and PCO2 during steady‐state breathing, and derived arterial PO2 via pulse oximetry. O2 deficit was defined as the difference between end‐tidal and calculated arterial PO2; consistent with the Bohr effect by utilizing end‐tidal PCO2. The ULCs were collected bilaterally, parasternal to mid‐axillary, at baseline and again 2.5 h post dive. Following the dive, although there was an impairment of pulmonary gas exchange, evident by an increase in O2 deficit from 10.9±4.5 mmHg at baseline to 22.9±5.1 mmHg 10‐min post dive (p=0.02), this deficit had normalized by 60‐min post. There was persistent hyperventilation up to 60 min post dive, reflected by reductions in end‐tidal PCO2 (p=0.02). PASP was unaltered post‐dive. Although ULCs trended to increase from baseline to 2.5 h post dive (3.7±3 to 10.4±13.2 comets; p=0.09), the delta change in ULC from baseline to post‐dive was positively correlated with depth (r=0.67, p=0.04) and, to a lesser extent, with both change in SpO2 (r=−0.62, p=0.06) and O2 deficit (r=0.58, p=0.08). The findings of this novel study suggest impairment in pulmonary gas exchange is present following diving to depth, even up to 10 min after surfacing. The mechanism(s) driving the slight hyperventilation are unclear, but potentially could be mediated via mild pulmonary edema and/or stimulation of juxtapulmonary capillary receptors. Together, there is transient impairment in gas exchange and associations with ULC during ‘modest’ dives. The development of pathological pulmonary edema, and severe and sustained impairment in pulmonary gas exchange, would seem likely at the forefront of breath‐hold diving performances (e.g, &gt;100 m). There remains little data regarding safe return‐to‐dive practices following a squeeze, and non‐invasive pulmonary gas exchange monitoring could provide valuable utility.Support or Funding InformationCanada Research Chair, NSERCThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

New Developments in Imaging Idiopathic Pulmonary Fibrosis With Hyperpolarized Xenon Magnetic Resonance Imaging.

Idiopathic pulmonary fibrosis (IPF) is a progressive pulmonary disease that is ultimately fatal. Although the diagnosis of IPF has been revolutionized by high-resolution computed tomography, this imaging modality still exhibits significant limitations, particularly in assessing disease progression and therapy response. The need for noninvasive regional assessment has become more acute in light of recently introduced novel therapies and numerous others in the pipeline. Thus, it will likely be valuable to complement 3-dimensional imaging of lung structure with 3-dimensional regional assessment of function. This challenge is well addressed by hyperpolarized (HP) Xe magnetic resonance imaging (MRI), exploiting the unique properties of this inert gas to image its distribution, not only in the airspaces, but also in the interstitial barrier tissues and red blood cells. This single-breath imaging exam could ultimately become the ideal, noninvasive tool to assess pulmonary gas-exchange impairment in IPF. This review article will detail the evolution of HP Xe MRI from its early development to its current state as a clinical research platform. It will detail the key imaging biomarkers that can be generated from the Xe MRI examination, as well as their potential in IPF for diagnosis, prognosis, and assessment of therapeutic response. We conclude by discussing the types of studies that must be performed for HP Xe MRI to be incorporated into the IPF clinical algorithm and begin to positively impact IPF disease diagnosis and management.

Non-invasive ventilation during surgery under neuraxial anaesthesia: apathophysiological perspective on application and benefits and asystematic literature review.

Unlike general anaesthesia, neuraxial anaesthesia (NA) reduces the burden and risk of respiratory adverse events in the post-operative period. However, both patients affected by chronic obstructive pulmonary disease (COPD) and chest wall disorders and/or neuromuscular diseases may experience the development or the worsening of respiratory failure, even during surgery performed under NA; this latter negatively affects the function of accessory respiratory muscles, resulting in a blunted central response to hypercapnia and possibly in an exacerbation of cardiac dysfunction (NA-induced relative hypovolemia). According to European Respiratory Society (ERS) and American Thoracic Society (ATS) guidelines, non-invasive ventilation (NIV) is effective in the post-operative period for the treatment of both impaired pulmonary gas exchange and ventilation, while the intra-operative use of NIV in association with NA is just anecdotally reported in the literature. Whilst NIV does not assure a protected patent airway and requires the patient's cooperation, it is a handy tool during surgery under NA: NIV is reported to be successful for treatment of acute respiratory failure; it may be delivered through the patient's home ventilator, may reverse hypoventilation induced by sedatives or inadvertent spread of anaesthetic up to cervical dermatomes, and allow the avoidance of intubation in patients affected by chronic respiratory failure, prolonging the time of non-invasiveness of respiratory support (i.e., neuromuscular patients needing surgery). All these advantages could make NIV preferable to oxygen in carefully selected patients.

Sleep and breathing disturbances in patients with chronic obstructive pulmonary disease traveling to altitude: a randomized trial.

Patients with chronic obstructive pulmonary disease (COPD) have impaired pulmonary gas exchange near sea level. The purpose of the current study was to investigate whether exposure to hypobaric hypoxia during a stay at altitude affects nocturnal oxygen saturation, breathing pattern, and sleep in patients with moderate to severe COPD. Thirty-two patients with COPD, median age 67 years, FEV1 59% predicted, PaO2 68 mmHg, living below 800 m, underwent polysomnography and questionnaire evaluations in Zurich (490 m), and in Swiss Alpine villages at 1650 and 2590 m, for two nights each, in random order. Mean nocturnal oxygen saturation (SpO2), the apnea-hypopnea index (AHI), and sleep structure were compared between altitudes. Polysomnography during the first night at each altitude revealed a reduced SpO2 at 1650 and 2590 m (medians 89% and 85%) compared with 490 m (92%, p <0.05 vs. higher altitudes) and a higher AHI (medians 26.8/hr and 55.7/hr) vs. 490 m (15.4/hr, p <0.05 vs. higher altitudes) due to emergence of frequent central apneas/hypopneas. At 2590 m, sleep efficiency (median 59%) and slow-wave sleep (median 17% of total sleep time) were reduced compared with 490 m (72% and 20%, respectively, p <0.05). In the morning after one night at 2590 m, patients estimated to have spent more time awake (median 110 min) than at 490 m (43 min, p <0.05) and felt slightly less alert. During a stay at moderate altitude, lowlanders with moderate to severe COPD experience nocturnal hypoxemia that induces central sleep apneas, altered sleep structure, and insomnia. These novel findings help us to counsel patients with COPD planning altitude travel. ClinicalTrials.gov: NCT01870830.

A New, Noninvasive Method of Measuring Pulmonary Gas Exchange: Results in Normal Subjects and Patients with Lung Disease

MethodsThe person breathes through a device that continually measures and displays the inspired and expired PO2 and PCO2. An oximeter is worn, and the arterial PO2 is calculated from the SpO2 and the oxygen dissociation curve, using the end–tidal PCO2 to account for the effect of PCO2 on the oxygen affinity of hemoglobin. The PO2 difference between the end‐tidal gas and the calculated arterial value is called the Oxygen Deficit. Since the calculation is only accurate when the arterial oxygen saturations are 94% or less, the normal subjects breathed 12.5% oxygen.ResultsStudies were made on 17 patients with a variety of pulmonary diseases who were attending an outpatient clinic. The mean oxygen deficit was 48.7 mm Hg, SE 3.1. This can be contrasted with a mean oxygen deficit of 4.0 mm Hg, SE 0.91 in a group of 30 normal subjects who were previously studied. The p value for the difference between the two groups was &lt; 0.0001. Within the normal subjects, the mean oxygen deficit for the 19 younger participants (ages 22–31) was 2.02 mm Hg, SE 0.84 while that in the 11 older participants (ages 47–88) was 7.53 mm Hg, SE 1.55. The p value for the difference between the young and old groups was 0.0015. The mean oxygen deficit in younger normal subjects is remarkably small. This implies that there is very little difference between the calculated arterial PO2 and the alveolar PO2, consistent with little impairment of gas exchange. However, the mean oxygen deficit in older normal subjects is significantly higher consistent with the increased Alveolar‐arterial (A‐a) PO2 gradient with age, which has been well documented in the literature. Analysis of the factors determining the magnitude of the oxygen deficit showed that the end–tidal PO2 was the most important factor, followed by the end–tidal PCO2, and the calculated arterial PO2. Interestingly the SpO2 had a minor influence in spite of the fact that the oximeter reading is frequently used to guide therapy. The analysis emphasizes the value of measuring the composition of alveolar gas in determining ventilation‐perfusion ratio inequality. Remarkably, this factor is largely ignored in the classical index of impaired pulmonary gas exchange using the ideal alveolar PO2 to calculate the A‐a O2 gradient. We argue that ignoring the actual alveolar value gives an incomplete picture of gas exchange in the lungs because the traditional index is heavily biased by lung units with low ventilation‐perfusion ratios. Therefore, by using the new index of oxygen deficit, we derive a more comprehensive measurement of gas exchange in the lungs.Support or Funding InformationSupported by MediPines IncThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A New, Noninvasive Method of Measuring Impaired Pulmonary Gas Exchange in Lung Disease: An Outpatient Study

It would be valuable to have a noninvasive method of measuring impaired pulmonary gas exchange in patients with lung disease and thus reduce the need for repeated arterial punctures. This study reports the results of using a new test in a group of outpatients attending a pulmonary clinic. Inspired and expired partial pressure of oxygen (PO2) and Pco2 are continually measured by small, rapidly responding analyzers. The arterial PO2 is calculated from the oximeter blood oxygen saturation level and the oxygen dissociation curve. The PO2 difference between the end-tidal gas and the calculated arterial value is called the oxygen deficit. Studies on 17 patients with a variety of pulmonary diseases are reported. The mean ± SE oxygen deficit was 48.7 ± 3.1mmHg. This finding can be contrasted with a mean oxygen deficit of 4.0 ± 0.88mmHg in a group of 31 normal subjects who were previously studied (P< .0001). The analysis emphasizes the value of measuring the composition of alveolar gas in determining ventilation-perfusion ratio inequality. This factor is largely ignored in the classic index of impaired pulmonary gas exchange using the ideal alveolar PO2 to calculate the alveolar-arterial oxygen gradient. The results previously reported in normal subjects and the present studies suggest that this new noninvasive test will be valuable in assessing abnormal gas exchange in the clinical setting.

Epinephrine Deteriorates Pulmonary Gas Exchange in a Rat Model of Bupivacaine-Induced Cardiotoxicity: A Threshold Dose of Epinephrine.

The study goal was to compare the effect of epinephrine in different doses on pulmonary gas exchange in a rat model of bupivacaine-induced cardiac depression. Twenty-four adult male Sprague-Dawley rats were divided into 4 groups (n = 6), and each group received a bupivacaine infusion (2.5 mg/kg per minute, 6 minutes) via the left femoral vein to induce cardiac depression. At the end of the bupivacaine infusion, each group was immediately given either isotonic sodium chloride solution (normal saline; NS group), 5-μg/kg epinephrine (Epi5 group), 10-μg/kg epinephrine (Epi10 group), or 20 μg/kg epinephrine (Epi20 group). Left atrial pressures were monitored for 20 minutes after epinephrine was administered (as was the NS group). Arterial blood gas analyses were performed before bupivacaine infusion and at the end of the 20-minute monitoring period. The Epi10 and Epi20 groups had lower pH (P = 0.02 and P < 0.001, respectively) and PaO2 (P = 0.049 and P < 0.001, respectively), and a higher PaCO2 (P < 0.001 and P < 0.001, respectively) compared with the NS group. There were no statistical differences between the Epi5 and NS groups in pH, PaCO2, or PaO2. Left atrial systolic pressure was higher in the Epi10 group (P = 0.002) and the Epi20 group (P < 0.001) within 2 minutes of epinephrine administration. There was no statistical difference between the Epi5 and NS groups in left atrial systolic pressure. A single injection of 10 μg/kg epinephrine or greater was associated with deterioration of pulmonary gas exchange in our rat model of bupivacaine induced cardiac depression.

Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome (ARDS).

Various animal models of lung injury exist to study the complex pathomechanisms of human acute respiratory distress syndrome (ARDS) and evaluate future therapies. Severe lung injury with a reproducible deterioration of pulmonary gas exchange and hemodynamics can be induced in anesthetized pigs using repeated lung lavages with warmed 0.9% saline (50 ml/kg body weight). Including standard respiratory and hemodynamic monitoring with clinically applied devices in this model allows the evaluation of novel therapeutic strategies (drugs, modern ventilators, extracorporeal membrane oxygenators, ECMO), and bridges the gap between bench and bedside. Furthermore, induction of lung injury with lung lavages does not require the injection of pathogens/endotoxins that impact on measurements of pro- and anti-inflammatory cytokines. A disadvantage of the model is the high recruitability of atelectatic lung tissue. Standardization of the model helps to avoid pitfalls, to ensure comparability between experiments, and to reduce the number of animals needed.

Exercise Ventilation in COPD: Influence of Systolic Heart Failure

ABSTRACTSystolic heart failure is a common and disabling co-morbidity of chronic obstructive pulmonary disease (COPD) which may increase exercise ventilation due to heightened neural drive and/or impaired pulmonary gas exchange efficiency. The influence of heart failure on exercise ventilation, however, remains poorly characterized in COPD. In a prospective study, 98 patients with moderate to very severe COPD [41 with coexisting heart failure; ‘overlap’ (left ventricular ejection fraction < 50%)] underwent an incremental cardiopulmonary exercise test (CPET). Compared to COPD, overlap had lower peak exercise capacity despite higher FEV1. Overlap showed lower operating lung volumes, greater ventilatory inefficiency and larger decrements in end-tidal CO2 (PETCO2) (P < 0.05). These results were consistent with those found in FEV1-matched patients. Larger areas under receiver operating characteristic curves to discriminate overlap from COPD were found for ventilation (E)-CO2 output CO2) intercept, E-CO2 slope, peak E/CO2 ratio and peak PETCO2. Multiple logistic regression analysis revealed that CO2 intercept ≤ 3.5 L/minute [odds ratios (95% CI) = 7.69 (2.61–22.65), P < 0.001] plus E-CO2 slope ≥ 34 [2.18 (0.73–6.50), P = 0.14] or peak E/CO2 ratio ≥ 37 [5.35 (1.96–14.59), P = 0.001] plus peak PETCO2 ≤ 31 mmHg [5.73 (1.42–23.15), P = 0.01] were indicative of overlapping. Heart failure increases the ventilatory response to metabolic demand in COPD. Variables reflecting excessive ventilation might prove useful to assist clinical interpretation of CPET responses in COPD patients presenting heart failure as co-morbidity.

From Berlin to Kigali: the sobering journey of acute respiratory distress syndrome.

What do Berlin, Kigali, and acute respiratory distress syndrome (ARDS) have in common? Berlin is the capital of Germany, brimming with attractiveness, science, culture, and a great lifestyle after the re-unification 25 years ago. Kigali is the largest city in Rwanda as well as its capital since the country’s independence in 1962, located at an altitude of 1,560 m. ARDS is characterized by dysregulated inflammation, inappropriate accumulation of leukocytes, uncontrolled activation of coagulation, and alveolar barrier disruption (1), often resulting in a life-threatening impairment of pulmonary gas exchange with hypoxemia, hypercapnia, and respiratory acidosis. The main causes of ARDS are direct (pneumonia, aspiration of gastric content) or indirect injuries (sepsis, massive transfusion, multi-trauma, peritonitis, pancreatitis). In European countries, the incidence of ARDS was estimated to be 50 cases per 100,000 person years, corresponding to approximately 40,000 cases per year for a country like Germany (2). ARDS is often associated with multiple-organ failure. A broad scenario of acute interventions for ARDS therapy have been investigated and recommended in recent years, but evidence that all these measures can decrease mortality is still limited (3). Mortality remains as high as 40–50% in major series (4).

Microcirculatory Disorders in Infant Respiratory Distress Syndrome (Morphological Study)

The purpose of the study is to evaluate morphological changes in lung vessels of preterm infants with the infant respiratory distress syndrome (IRDS). Material and Methods. Case history records and postmortem examination protocols of 70 preterm infants who died because of severe respiratory compromise as a result of IRDS were analyzed. All newborns were divided into three groups: the IRDS group included 25 (35.7%) infants who died due to IRDS (no surfactant); the Curosurf group was composed of 26 (37.2%) infants who received an exogenous surfactant Curosurf as a part of a complex therapy; the Surfactant BL group included 19 (27.1%) infants receiving Surfactant BL. Histological and morphometric examinations of lung vessels were performed. The Kernogan index calculated as the ratio between the lumen diameter and the wall thickness was determined. Results. The arterial bed of newborns in the IRDS and Curosurf groups was composed of vessels having up to several μm in diameter. Larger arteries (51—100 μm in diameter) and arteries of more than 100 μm in diameter are distributed uniformly and comprise 1/3 of the total number of visualized vessels. The invert correlation of the arterial vascular bed was typical for the infants in the Surfactant BL group: arteries of 50 μm in diameter comprise 30% of all vessels, and arteries of more than 100 μm in diameter prevail. The venous bed of newborns consisted mainly of vessels having less than 50 μm in diameter. The greatest changes in the arterial wall thickness (ТСА) are typical for vessels with a total diameter of more than 51 μm. In babies of the IRDS group, the greatest (ТСА) changes were typical for arteries of 51—100 μm in diameter. Changes in arterial walls (&gt;101 μm) were typical for the Surfactant BL group. Unlike other groups, in the Curosurf group, no significant changes in the parameters under the test were found (P&gt;0.05). In this group (as compared to IRDS and Surfactant BL groups), there were minimal changes in vein characteristics and the minimal venous wall thickness (ТСv) (&gt;100 μm in diameter). The Kernogan index for veins with small diameter was minimal. Conclusion. Evaluation of the microcirculatory bed of lungs in IRDS patients is an urgent problem because the pulmonary gas exchange impairment in preterm infants is primarily caused by circulatory and microcirculatory disorders of various degrees of severity that result from anatomic and functional immaturity of the lung micro circulatory bed. In cases of unfavorable outcomes, dilation of arterial and venous lumen and vascular wall thickening might be considered as principal signs of microcirculatory disorders. Surfactants affect changes in the diameter of lumen of lung vessels, especially those with a diameter more than 50 μm, presumably improving the blood supply of the lungs. Minimal changes of tested parameters were typical for newborns on Curosurf versus IRDS and Surfactant BL groups of infants.

Mouse Models of Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is a severe pulmonary reaction requiring hospitalization, which is incited by many causes, including bacterial and viral pneumonia as well as near drowning, aspiration of gastric contents, pancreatitis, intravenous drug use, and abdominal trauma. In humans, ARDS is very well defined by a list of clinical parameters. However, until recently no consensus was available regarding the criteria of ARDS that should be evident in an experimental animal model. This lack was rectified by a 2011 workshop report by the American Thoracic Society, which defined the main features proposed to delineate the presence of ARDS in laboratory animals. These should include histological changes in parenchymal tissue, altered integrity of the alveolar capillary barrier, inflammation, and abnormal pulmonary function. Murine ARDS models typically are defined by such features as pulmonary edema and leukocyte infiltration in cytological preparations of bronchoalveolar lavage fluid and/or lung sections. Common pathophysiological indicators of ARDS in mice include impaired pulmonary gas exchange and histological evidence of inflammatory infiltrates into the lung. Thus, morphological endpoints remain a vital component of data sets assembled from animal ARDS models.