The pathophysiology of patent foramen ovale and its related complications.

The foramen ovale plays a vital role in sustaining life in-utero; however, a patent foramen ovale (PFO) after birth has been associated with pathologic sequelae in the systemic circulation including stroke/transient ischemic attack (TIA), migraine, high altitude pulmonary edema, decompression illness, platypnea-orthodeoxia syndrome (POS) and worsened severity of obstructive sleep apnea. Importantly, each of these conditions is most commonly observed among specific age groups: migraine in the 20 to 40s, stroke/TIA in the 30-50s and POS in patients >50 years of age. The common and central pathophysiologic mechanism in each of these conditions is PFO-mediated shunting of blood and its contents from the right to the left atrium. PFO-associated pathologies can therefore be divided into (1) paradoxical systemic embolization and (2) right to left shunting (RLS) of blood through the PFO. Missing in the extensive literature on these clinical syndromes are mechanistic explanations for the occurrence of RLS, including timing and the volume of blood shunted, the impact of age on RLS, and the specific anatomical pathway that blood takes from the venous system to the left atrium. Visualization of the flow pattern graphically illustrates the underlying RLS and provides a greater understanding of the critical flow dynamics that determine the frequency, volume, and pathway of flow. In the present review, we describe the important role of foramen ovale in in-utero physiology, flow visualization in patients with PFO, as well as contributing factors that work in concert with PFO to result in the diverse pathophysiological sequelae.

Modulation of angiopoietin-2 and Tie2: Organ specific effects of microvascular leakage and edema in mice.

INTRODUCTION: Critical illness is associated with organ failure, in which endothelial hyperpermeability and tissue edema play a major role. The endothelial angiopoietin/Tie2 system, a regulator of endothelial permeability, is dysbalanced during critical illness. Elevated circulating angiopoietin-2 and decreased Tie2 receptor levels are reported, but it remains unclear whether they cause edema independent of other critical illness-associated alterations. Therefore, we have studied the effect of angiopoietin-2 administration and/or reduced Tie2 expression on microvascular leakage and edema under normal conditions. METHODS: Transgenic male mice with partial deletion of Tie2 (heterozygous exon 9 deletion, Tie2+/-) and wild-type controls (Tie2+/+) received 24 or 72 pg/g angiopoietin-2 or PBS as control (n = 12 per group) intravenously. Microvascular leakage and edema were determined by Evans blue dye (EBD) extravasation and wet-to-dry weight ratio, respectively, in lungs and kidneys. Expression of molecules related to endothelial angiopoietin/Tie2 signaling were determined by ELISA and RT-qPCR. RESULTS: In Tie2+/+ mice, angiopoietin-2 administration increased EBD extravasation (154 %, p < 0.05) and wet-to-dry weight ratio (133 %, p < 0.01) in lungs, but not in the kidney compared to PBS. Tie2+/- mice had higher pulmonary (143 %, p < 0.001), but not renal EBD extravasation, compared to wild-type control mice, whereas a more pronounced wet-to-dry weight ratio was observed in lungs (155 %, p < 0.0001), in contrast to a minor higher wet-to-dry weight ratio in kidneys (106 %, p < 0.05). Angiopoietin-2 administration to Tie2+/- mice did not further increase pulmonary EBD extravasation, pulmonary wet-to-dry weight ratio, or renal wet-to-dry weight ratio. Interestingly, angiopoietin-2 administration resulted in an increased renal EBD extravasation in Tie2+/- mice compared to Tie2+/- mice receiving PBS. Both angiopoietin-2 administration and partial deletion of Tie2 did not affect circulating angiopoietin-1, soluble Tie2, VEGF and NGAL as well as gene expression of angiopoietin-1, -2, Tie1, VE-PTP, ELF-1, Ets-1, KLF2, GATA3, MMP14, Runx1, VE-cadherin, VEGFα and NGAL, except for gene and protein expression of Tie2, which was decreased in Tie2+/- mice compared to Tie2+/+ mice. CONCLUSIONS: In mice, the microvasculature of the lungs is more vulnerable to angiopoietin-2 and partial deletion of Tie2 compared to those in the kidneys with respect to microvascular leakage and edema.

Periprocedural acute haemodynamic decompensation during substrate-based ablation of scar-related ventricular tachycardia: a rare and unpredictable event.

AIMS: Patients with structural heart disease (SHD) undergoing catheter ablation (CA) for ventricular tachycardia (VT) are at considerable risk of periprocedural complications, including acute haemodynamic decompensation (AHD). The PAINESD score was proposed to predict the risk of AHD. The goal of this study was to validate the PAINESD score using the retrospective analysis of data from a large-volume heart centre. METHODS AND RESULTS: Patients who had their first radiofrequency CA for SHD-related VT between August 2006 and December 2020 were included in the study. Procedures were mainly performed under conscious sedation. Substrate mapping/ablation was performed primarily during spontaneous rhythm or right ventricular pacing. A purposely established institutional registry for complications of invasive procedures was used to collect all periprocedural complications that were subsequently adjudicated using the source medical records. Acute haemodynamic decompensation triggered by CA procedure was defined as intraprocedural or early post-procedural (<12 h) development of acute pulmonary oedema or refractory hypotension requiring urgent intervention. The study cohort consisted of 1124 patients (age, 63 ± 13 years; males, 87%; ischaemic cardiomyopathy, 67%; electrical storm, 25%; New York Heart Association Class, 2.0 ± 1.0; left ventricular ejection fraction, 34 ± 12%; diabetes mellitus, 31%; chronic obstructive pulmonary disease, 12%). Their PAINESD score was 11.4 ± 6.6 (median, 12; interquartile range, 6-17). Acute haemodynamic decompensation complicated the CA procedure in 13/1124 = 1.2% patients and was not predicted by PAINESD score with AHD rates of 0.3, 1.8, and 1.1% in subgroups by previously published PAINESD terciles (<9, 9-14, and >14). However, the PAINESD score strongly predicted mortality during the follow-up. CONCLUSION: Primarily substrate-based CA of SHD-related VT performed under conscious sedation is associated with a substantially lower rate of AHD than previously reported. The PAINESD score did not predict these events. The application of the PAINESD score to the selection of patients for pre-emptive mechanical circulatory support should be reconsidered.

Hyperoxia-Induced Secondary Respiratory Failure in a Systemic Ischaemia-Reperfusion Injury.

Recent studies revealed that excessive supplemental oxygen, such as inhaled 100% O2, damages various organ functions in post-cardiac arrest (CA) patients. Optimal indicators of supplemental oxygen are therefore important to prevent hyperoxic organ injuries. In this study, we evaluated a hyperoxic pulmonary injury and assessed the association between alveolar-arterial oxygen difference (AaDO2) and a degree of lung oedema. In this study, we focused on the hyperoxia-induced lung injury and its association with changes of gas-exchange parameters in post-CA rats. Rats were resuscitated from 10 min of asphyxial CA and stratified into two groups: those with inhaled 100% O2 (CA-FiO2 1.0) and those with 30% O2 (CA-FiO2 0.3). We prepared a sham surgery group for comparison (sham-FiO2 0.3). After 2 h, animals were sacrificed, and the lung wet-to-dry (W/D) weight ratio was measured. We collected blood gas results and measured the ratio of partial pressure arterial oxygen and fraction of inspired oxygen (p/f ratio), and calculated AaDO2. The lung W/D ratio in the CA-FiO2 1.0 group (5.8 ± 0.26) was higher than in the CA-FiO2 0.3 (4.6 ± 0.42) and sham-FiO2 0.3 groups (4.6 ± 0.38, p < 0.01). There was a significant difference in AaDO2 between CA-FiO2 1.0 (215 ± 49.3) and, CA-FiO2 0.3 (36.8 ± 32.3), and sham-FiO2 0.3 groups (49.0 ± 20.5, p < 0.01). There were also significant changes in pH and blood lactate levels in the early phase among the three groups. AaDO2 showed the strongest correlation with W/D ratio (r = 0.9415, p < 0.0001), followed by pH (r = -0.5131, p = 0.0294) and p/f ratio (r = -0.3861, p = 0.1135). Hyperoxic injury might cause the pulmonary oedema after CA. Measuring respiratory quotient (RQ) in rodents enabled an accurate calculation for AaDO2 at a variety level of inhaled O2. Given that AaDO2 measurement is non-invasive, we therefore consider AaDO2 to be a potentially optimal indicator of post-CA hyperoxic pulmonary injury.

Cardiovascular effects of breath-hold diving at altitude.

Hypoxia, centralization of blood in pulmonary vessels, and increased cardiac output during physical exertion are the pathogenetic pathways of acute pulmonary edema observed during exposure to extraordinary environments. This study aimed to evaluate the effects of breath-hold diving at altitude, which exposes simultaneously to several of the stimuli mentioned above. To this aim, 11 healthy male experienced divers (age 18-52y) were evaluated (by Doppler echocardiography, lung echography to evaluate ultrasound lung B-lines (BL), hemoglobin saturation, arterial blood pressure, fractional NO (Nitrous Oxide) exhalation in basal condition (altitude 300m asl), at altitude (2507m asl) and after breath-hold diving at altitude. A significant increase in E/e' ratio (a Doppler-echocardiographic index of left atrial pressure) was observed at altitude, with no further change after the diving session. The number of BL significantly increased after diving at altitude as compared to basal conditions. Finally, fractional exhaled nitrous oxide was significantly reduced by altitude; no further change was observed after diving. Our results suggest that exposure to hypoxia may increase left ventricular filling pressure and, in turn, pulmonary capillary pressure. Breath-hold diving at altitude may contribute to interstitial edema (as evaluated by BL score), possibly because of physical efforts made during a diving session. The reduction of exhaled nitrous oxide at altitude confirms previous reports of nitrous oxide reduction after repeated exposure to hypoxic stimuli. This finding should be further investigated since reduced nitrous oxide production in hypoxic conditions has been reported in subjects prone to high-altitude pulmonary edema.

What is the impact of microvascular complications of diabetes on severe COVID-19?

Evidence suggests severe coronavirus disease-19 (COVID-19) infection is characterised by pulmonary and systemic microvasculature dysfunction, specifically, acute endothelial injury, hypercoagulation and increased capillary permeability. Diabetes, which is also characterised by vascular injury in itself, confers an increased risk of adverse COVID-19 outcomes. It has been suggested that pre-existing endothelial dysfunction and microvascular disease in diabetes will exacerbate the vascular insults associated with COVID-19 and thus lead to increased severity of COVID-19 infection. In this article, we evaluate the current evidence exploring the impact of microvascular complications, in the form of diabetic retinopathy and nephropathy, in individuals with COVID-19 and diabetes. Future insights gained from exploring the microvascular injury patterns and clinical outcomes may come to influence care delivery algorithms for either of these conditions.

Endothelial cell Piezo1 mediates pressure-induced lung vascular hyperpermeability via disruption of adherens junctions.

Increased pulmonary microvessel pressure experienced in left heart failure, head trauma, or high altitude can lead to endothelial barrier disruption referred to as capillary "stress failure" that causes leakage of protein-rich plasma and pulmonary edema. However, little is known about vascular endothelial sensing and transduction of mechanical stimuli inducing endothelial barrier disruption. Piezo1, a mechanosensing ion channel expressed in endothelial cells (ECs), is activated by elevated pressure and other mechanical stimuli. Here, we demonstrate the involvement of Piezo1 in sensing increased lung microvessel pressure and mediating endothelial barrier disruption. Studies were made in mice in which Piezo1 was deleted conditionally in ECs (Piezo1iΔEC ), and lung microvessel pressure was increased either by raising left atrial pressure or by aortic constriction. We observed that lung endothelial barrier leakiness and edema induced by raising pulmonary microvessel pressure were abrogated in Piezo1iΔEC mice. Piezo1 signaled lung vascular hyperpermeability by promoting the internalization and degradation of the endothelial adherens junction (AJ) protein VE-cadherin. Breakdown of AJs was the result of activation of the calcium-dependent protease calpain and degradation of the AJ proteins VE-cadherin, ß-catenin, and p120-catenin. Deletion of Piezo1 in ECs or inhibition of calpain similarly prevented reduction in the AJ proteins. Thus, Piezo1 activation in ECs induced by elevated lung microvessel pressure mediates capillary stress failure and edema formation secondary to calpain-induced disruption of VE-cadherin adhesion. Inhibiting Piezo1 signaling may be a useful strategy to limit lung capillary stress failure injury in response to elevated vascular pressures.

Left ventricular depression and pulmonary edema in rats after short-term normobaric hypoxia: effects of adrenergic blockade and reduced fluid load.

Acute normobaric hypoxia may induce pulmonary injury with edema (PE) and inflammation. Hypoxia is accompanied by sympathetic activation. As both acute hypoxia and high plasma catecholamine levels may elicit PE, we had originally expected that adrenergic blockade may attenuate the severity of hypoxic pulmonary injury. In particular, we investigated whether administration of drugs with reduced fluid load would be beneficial with respect to both cardiocirculatory and pulmonary functions in acute hypoxia. Rats were exposed to normobaric hypoxia (10% O2) over 1.5 or 6 h and received 0.9% NaCl or adrenergic blockers either as infusion (1 ml/h, increased fluid load) or injection (0.5 ml, reduced fluid load). Control animals were kept in normoxia and received infusions or injections of 0.9% NaCl. After 6 h of hypoxia, LV inotropic function was maintained with NaCl injection but decreased significantly with NaCl infusion. Adrenergic blockade induced a similar LV depression when fluid load was low, but did not further deteriorate LV depression after 6 h of infusion. Reduced fluid load also attenuated pulmonary injury after 6 h of hypoxia. This might be due to an effective fluid drainage into the pleural space. Adrenergic blockade could not prevent PE. In general, increased fluid load and impaired LV inotropic function promote the development of PE in acute hypoxia. The main physiologic conclusion from this study is that fluid reduction under hypoxic conditions has a protective effect on cardiopulmonary function. Consequently, appropriate fluid management has particular importance to subjects in hypoxic conditions.

Standardization of methods for sampling the distal airspace in mechanically ventilated patients using heat moisture exchange filter fluid.

Noninvasive sampling of the distal airspace in patients with acute respiratory distress syndrome (ARDS) has long eluded clinical and translational researchers. We recently reported that fluid collected from heat moisture exchange (HME) filters closely mirrors fluid directly aspirated from the distal airspace. In the current study, we sought to determine fluid yield from different HME types, optimal HME circuit dwell time, and reliability of HME fluid in reflecting the distal airspace. We studied fluid yield from four different filter types by loading increasing volumes of saline and measuring volumes of fluid recovered. We collected filters after 1, 2, and 4 h of dwell time for measurement of fluid volume and total protein from 13 subjects. After identifying 4 h as the optimal dwell time, we measured total protein and IgM in HME fluid from 42 subjects with ARDS and nine with hydrostatic pulmonary edema (HYDRO). We found that the fluid yield varies greatly by filter type. With timed sample collection, fluid recovery increased with increasing circuit dwell time with a median volume of 2.0 mL [interquartile range (IQR) 1.2-2.7] after 4 h. Total protein was higher in the 42 subjects with ARDS compared with nine with HYDRO [median 708 µg/mL (IQR 244-2017) vs. 364 µg/mL (IQR 136-578), P = 0.047], confirming that total protein concentration in HME is higher in ARDS compared with hydrostatic edema. These studies establish a standardized HME fluid collection protocol and confirm that HME fluid analysis is a novel noninvasive tool for the study of the distal airspace in ARDS.

Probable positive effects of the photobiomodulation as an adjunctive treatment in COVID-19: A systematic review.

BACKGROUND: COVID-19, as a newly-emerged viral infection has now spread all over the world after originating in Wuhan, China. Pneumonia is the hallmark of the disease, with dyspnea in half of the patients and acute respiratory distress syndrome (ARDS) in up to one -third of the cases. Pulmonary edema, neutrophilic infiltration, and inflammatory cytokine release are the pathologic signs of this disease. The anti-inflammatory effect of the photobiomodulation (PBM) has been confirmed in many previous studies. Therefore, this review study was conducted to evaluate the direct effect of PBM on the acute lung inflammation or ARDS and also accelerating the regeneration of the damaged tissues. The indirect effects of PBM on modulation of the immune system, increasing the blood flow and oxygenation in other tissues were also considered. METHODOLOGY: The databases of PubMed, Cochrane library, and Google Scholar were searched to find the relevant studies. Keywords included the PBM and related terms, lung inflammation, and COVID-19 -related signs. Studies were categorized with respect to the target tissue, laser parameters, and their results. RESULTS: Seventeen related papers were included in this review. All of them were in animal models. They showed that the PBM could significantly decrease the pulmonary edema, neutrophil influx, and generation of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), intracellular adhesion molecule (ICAM), reactive oxygen species (ROS), isoform of nitric oxide synthase (iNOS), and macrophage inflammatory protein 2 (MIP-2)). CONCLUSION: Our findings revealed that the PBM could be helpful in reducing the lung inflammation and promoting the regeneration of the damaged tissue. PBM can increase the oxygenation indirectly in order to rehabilitate the affected organs. Thus, the infra-red lasers or light-emitting diodes (LEDs) are recommended in this regard.

Cerebral perfusion pressure and autoregulation in eclampsia-a case control study.

BACKGROUND: Dynamic cerebral autoregulation and cerebral perfusion pressure are altered in pregnancies complicated by preeclampsia compared with normotensive pregnancies, but the connections of dynamic cerebral autoregulation, cerebral perfusion pressure, and cerebral complications in preeclampsia remain unclear. OBJECTIVE: This study aimed to assess dynamic cerebral autoregulation and cerebral perfusion pressure after delivery in women with eclampsia, in women with preeclampsia both with and without severe features, and in normotensive women. STUDY DESIGN: This was a prospective case control study at a large referral hospital in Cape Town, South Africa. The recruitment of participants was done at diagnosis (cases) or at admission for delivery (controls). Transcranial Doppler examinations with continuous noninvasive blood pressure measurements and end-tidal CO2 monitoring were conducted for cases and controls after delivery. Cerebral perfusion pressure and dynamic cerebral autoregulation index were calculated, and values were compared among groups. RESULTS: We included 16 women with eclampsia, 18 women with preeclampsia with severe features, 32 women with preeclampsia without severe features, and 21 normotensive women with uncomplicated pregnancies. Dynamic cerebral autoregulation was depressed in pregnant women with eclampsia; (autoregulation index, 3.9; interquartile range, 3.1-5.2) compared with all other groups (those with preeclampsia with severe features, autoregulation index, 5.6 [interquartile range, 4.4-6.8]; those with preeclampsia without severe features, autoregulation index, 6.8 [interquartile range, 5.1-7.4]; and normotensive controls, autoregulation index, 7.1 [interquartile range, 6.1-7.9]). Pregnant women with eclampsia had increased cerebral perfusion pressure (109.5 mm Hg; interquartile range, 91.2-130.9) compared with those with preeclampsia without severe features and those with normal blood pressure (84 mm Hg [interquartile range, 73.0-122.0] and 80.0 mm Hg [interquartile range, 67.5-92.0], respectively); furthermore, there was no difference in cerebral perfusion pressure between pregnant women with eclampsia and pregnant women with preeclampsia with severe features (109.5 mm Hg [interquartile range, 91.2-130.9] vs 96.5 mm Hg [interquartile range, 75.8-110.5]). CONCLUSION: Cerebral perfusion pressure and dynamic cerebral autoregulation are altered in eclampsia and may be important in the pathophysiological pathway and constitute a therapeutic target in the prevention of cerebral complications in preeclampsia.

The impact of the definition of preeclampsia on disease diagnosis and outcomes: a retrospective cohort study.

BACKGROUND: The diagnostic criteria for preeclampsia have evolved from the traditional definition of de novo hypertension and proteinuria to a broader definition of hypertension with evidence of end-organ dysfunction. Although this change is endorsed by various societies such as the International Society for the Study of Hypertension in Pregnancy and the American College of Obstetricians and Gynecologists, there remains controversy with regard to the implementation of broader definitions and the most appropriate definition of end-organ dysfunction. OBJECTIVE: This study aimed to assess the impact of different diagnostic criteria for preeclampsia on rates of disease diagnosis, disease severity, and adverse outcomes and to identify associations between each component of the different diagnostic criteria and adverse pregnancy outcomes. STUDY DESIGN: We performed a retrospective cohort study of singleton pregnancies at Monash Health between January 1, 2016 and July 31, 2018. Within this population, all cases of gestational hypertension and preeclampsia were reclassified according to the International Society for the Study of Hypertension in Pregnancy 2001, American College of Obstetricians and Gynecologists 2018, and International Society for the Study of Hypertension in Pregnancy 2018 criteria. Differences in incidence of preeclampsia and maternal and perinatal outcomes were compared between the International Society for the Study of Hypertension in Pregnancy 2001 group and the extra cases identified by American College of Obstetricians and Gynecologists 2018 and International Society for the Study of Hypertension in Pregnancy 2018. Outcomes assessed included biochemical markers of preeclampsia, a composite of adverse maternal outcomes, and a composite of adverse perinatal outcomes. Multiple logistic regression analysis was also performed to assess each component of the American College of Obstetricians and Gynecologists 2018 and International Society for the Study of Hypertension in Pregnancy 2018 criteria and their associations with adverse maternal and perinatal outcomes. RESULTS: Of 22,094 pregnancies, 751 (3.4%) women had preeclampsia as defined by any of the 3 criteria. Compared with International Society for the Study of Hypertension in Pregnancy 2001, the American College of Obstetricians and Gynecologists 2018 criteria identified an extra 42 women (n=654 vs n=696, 6.4% relative increase) with preeclampsia, and International Society for the Study of Hypertension in Pregnancy 2018 identified an extra 97 women (n=654 vs n=751, 14.8% relative increase). The additional women identified by International Society for the Study of Hypertension in Pregnancy 2018 exhibited a milder form of disease with lower rates of severe hypertension (62.4% vs 44.3%; P<.01) and magnesium sulfate use (11.9% vs 4.1%; P<.05) and a trend toward lower rates of adverse maternal outcomes (9.8% vs 4.1%). These women also delivered at a later gestation, and their babies had a lower number of neonatal intensive care unit admissions and adverse perinatal outcomes. Objective features such as fetal growth restriction, thrombocytopenia, renal and liver impairment, and proteinuria were associated with an increased risk of adverse maternal and perinatal outcomes, whereas subjective neurologic features demonstrated poorer associations. CONCLUSION: Implementation of broader definitions of preeclampsia will result in an increased incidence of disease diagnosis. However, because women who exclusively fulfill the new criteria have a milder phenotype of the disease, it remains uncertain whether this will translate to improved outcomes.

The fluid management and hemodynamic characteristics of PiCCO employed on young children with severe hand, foot, and mouth disease-a retrospective study.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is an acute infectious disease caused by human enterovirus 71 (EV71), coxsackievirus, or echovirus, which is particularly common in preschool children. Severe HFMD is prone to cause pulmonary edema before progressing to respiratory and circulatory failure; thus hemodynamic monitoring and fluid management are important to the treatment process. METHODS: We did a review of young patients who had been successfully treated in our department for severe HFMD, which had been caused by EV71. A total of 20 patients met the inclusion criteria. Eight cases were monitored by the pulse indicator continuous cardiac output (PiCCO) technique, and fluid management was administered according to its parameters. With regard to the treatment with PiCCO monitoring, patients were divided into two groups: the PiCCO group (8 patients) and the control group (12 patients). The groups were then compared comprehensively to evaluate whether PiCCO monitoring could improve patients' clinical outcomes. RESULTS: After analysis, the findings informed that although PiCCO failed to shorten the length of ICU stay, reduce the days of vasoactive drug usage, or lower the number of cases which required mechanical ventilation, PiCCO did reduce the incidence of fluid overload (p = 0.085) and shorten the days of mechanical ventilation (p = 0.028). After effective treatment, PiCCO monitoring indicated that the cardiac index (CI) increased gradually(p < 0.0001), in contrast to their pulse (P, p < 0.0001), the extra vascular lung water index (EVLWI, p < 0.0001), the global end diastolic volume index (GEDVI, p = 0.0043), and the systemic vascular resistance index (SVRI, p < 0.0001), all of which decreased gradually. CONCLUSION: Our study discovered that PiCCO hemodynamic monitoring in young children with severe HFMD has some potential benefits, such as reducing fluid overload and the duration of mechanical ventilation. However, whether it can ameliorate the severity of the disease, reduce mortality, or prevent multiple organ dysfunction remain to be further investigated.

Point-of-Care Lung Ultrasound Pattern in Healthy Parturients: Prevalence of Pulmonary Interstitial Syndrome Following Vaginal Delivery, Elective and Unplanned Intrapartum Cesarean Delivery.

BACKGROUND: Pregnancy-related cardiovascular physiologic changes increase the likelihood of pulmonary edema, with the risk of fluid extravasating into the pulmonary interstitium being potentially at a maximum during the early postpartum period. Data on the impact of labor and peripartum hemodynamic strain on lung ultrasound (LUS) are limited, and the prevalence of subclinical pulmonary interstitial syndrome in peripartum women is poorly described. The primary aim of this exploratory study was to estimate the prevalence of pulmonary interstitial syndrome in healthy term parturients undergoing vaginal (VD), elective (eCD), and unplanned intrapartum cesarean deliveries (uCD). Secondary aims were to estimate the prevalence of positive lung regions (≥3 B-lines on LUS per region) and to assess the associations between positive lung regions and possible contributing factors. METHODS: In this prospective observational cohort study, healthy women at term undergoing VD, eCD, or uCD were enrolled. Following international consensus recommendations, a LUS examination was performed within 4 hours after delivery applying an 8-region technique. Pulmonary interstitial syndrome was defined by the presence of 2 or more positive lung regions per hemithorax. Ultrasound studies were reviewed by 2 blinded reviewers and assessed for interobserver reliability. RESULTS: Seventy-five women were assessed (n = 25 per group). No pulmonary interstitial syndrome was found in the VD and eCD groups (each 0 of 25; 0%, 95% confidence interval [CI], 0-13.7). Pulmonary interstitial syndrome was found in 2 of 25 (8%, 95% CI, 1-26) women undergoing an uCD (P = .490 for VD versus uCD and P = .490 for eCD versus uCD). In 1 woman, this correlated clinically with the development of pulmonary edema. One or more positive lung regions were present in 5 of 25 (20%), 6 of 25 (24%), and 11 of 25 (44%) parturients following VD, eCD, and uCD, respectively (P = .136). Positive lung regions were predominantly found in lateral lung regions. The number of positive lung regions showed a weak correlation with patient age (r = 0.25, 95% CI, 0.05-0.47; P = .033). No significant association was found between LUS pattern and parity, duration of labor, labor augmentation, labor induction, estimated total intravenous fluid intake, or net intravenous fluid intake. CONCLUSIONS: Although many focal areas of increased extravascular lung water (20%-44% prevalence) can be identified on LUS, the overall prevalence of pulmonary interstitial syndrome was 2.7% (2 of 75; 95% CI, 0.3-9.3) among healthy term parturients soon after delivery. Focal areas of positive lung water regions were weakly correlated with maternal age.

A method for translational rat ex vivo lung perfusion experimentation.

The application of ex vivo lung perfusion (EVLP) has significantly increased the successful clinical use of marginal donor lungs. While large animal EVLP models exist to test new strategies to improve organ repair, there is currently no rat EVLP model capable of maintaining long-term lung viability. Here, we describe a new rat EVLP model that addresses this need, while enabling the study of lung injury due to cold ischemic time (CIT). The technique involves perfusing and ventilating male Lewis rat donor lungs for 4 h before transplanting the left lung into a recipient rat and then evaluating lung function 2 h after reperfusion. To test injury within this model, lungs were divided into groups and exposed to different CITs (i.e., 20 min, 6 h, 12 h, 18 h and 24 h). Experiments involving the 24-h-CIT group were prematurely terminated due to the development of severe edema. For the other groups, no differences in the ratio of arterial oxygen partial pressure to fractional inspired oxygen ([Formula: see text]/[Formula: see text]) were observed during EVLP; however, lung compliance decreased over time in the 18-h group (P = 0.012) and the [Formula: see text]/[Formula: see text] of the blood from the left pulmonary vein 2 h after transplantation was lower compared with 20-min-CIT group (P = 0.0062). This new model maintained stable lung function during 4-h EVLP and after transplantation when exposed to up to 12 h of CIT.

M1 macrophage features in severe Plasmodium falciparum malaria patients with pulmonary oedema.

BACKGROUND: Pulmonary oedema (PE) is a serious complication of Plasmodium falciparum malaria which can lead to acute lung injury in severe cases. Lung macrophages are activated during malaria infection due to a complex host-immune response. The molecular basis for macrophage polarization is still unclear but understanding the predominant subtypes could lead to new therapeutic strategies where the diseases present with lung involvement. The present study was designed to study the polarization of lung macrophages, as M1 or M2 macrophages, in the lungs of severe P. falciparum malaria patients, with and without evidence of PE. METHODS: Lung tissue samples, taken from patients who died from severe P. falciparum malaria, were categorized into severe malaria with PE and without PE (non-PE). Expression of surface markers (CD68+, all macrophages; CD40+, M1 macrophage; and CD163+, M2 macrophage) on activated lung macrophages was used to quantify M1/M2 macrophage subtypes. RESULTS: Lung injury was demonstrated in malaria patients with PE. The expression of CD40 (M1 macrophage) was prominent in the group of severe P. falciparum malaria patients with PE (63.44 ± 1.98%), compared to non-PE group (53.22 ± 3.85%, p < 0.05), whereas there was no difference observed for CD163 (M2 macrophage) between PE and non-PE groups. CONCLUSIONS: The study demonstrates M1 polarization in lung tissues from severe P. falciparum malaria infections with PE. Understanding the nature of macrophage characterization in malaria infection may provide new insights into therapeutic approaches that could be deployed to reduce lung damage in severe P. falciparum malaria.

A Morphological and Quantitative Analysis of Lung CT Scan in Patients With Acute Respiratory Distress Syndrome and in Cardiogenic Pulmonary Edema.

BACKGROUND: The acute respiratory distress syndrome (ARDS) and cardiogenic pulmonary edema (CPE) are both characterized by an increase in lung edema that can be measured by computed tomography (CT). The aim of this study was to compare possible differences between patients with ARDS and CPE in the morphologic pattern, the aeration, and the amount and distribution of edema within the lung. METHODS: Lung CT was performed at a mean positive end-expiratory pressure level of 5 cm H2O in both groups. The morphological evaluation was performed by two radiologists, while the quantitative evaluation was performed by a dedicated software. RESULTS: A total of 60 patients with ARDS (20 mild, 20 moderate, 20 severe) and 20 patients with CPE were enrolled. The ground-glass attenuation regions were similarly present among the groups, 8 (40%), 8 (40%), 14 (70%), and 10 (50%), while the airspace consolidations were significantly more present in ARDS. The lung gas volume was significantly lower in severe ARDS compared to CPE (830 [462] vs 1120 [832] mL). Moving from the nondependent to the dependent lung regions, the not inflated lung tissue significantly increased, while the well inflated tissue decreased (ρ = 0.96-1.00, P < .0001). Significant differences were found between ARDS and CPE mostly in dependent regions. In severe ARDS, the estimated edema was significantly higher, compared to CPE (757 [740] vs 532 [637] g). CONCLUSIONS: Both ARDS and CPE are characterized by a similar presence of ground-glass attenuation and different airspace consolidation regions. Acute respiratory distress syndrome has a higher amount of not inflated tissue and lower amount of well inflated tissue. However, the overall regional distribution is similar within the lung.

Pulmonary vasodilators can lead to various complications in pulmonary "arterial" hypertension associated with congenital heart disease.

Congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) is one of the major complications in patients with CHD. A timely closure of the left-to-right shunt will generally result in the normalization of the pulmonary hemodynamics, but a few patients have severe prognosis in their early childhood. We hypothesized that wide-ranging pathological mechanism in PAH could elucidate the clinical state of severe CHD-PAH. Using electronic medical records, we retrospectively analyzed six infants with severe CHD-PAH who had treatment-resistant PH. All patients were born with congenital malformation syndrome. After starting on a pulmonary vasodilator, five of the six patients developed complications including pulmonary edema and interstitial lung disease (ILD), and four patients had alveolar hemorrhage. After steroid therapy, the clinical condition improved in four patients, but two patients died. The autopsy findings in one of the deceased patients indicated the presence of recurrent alveolar hemorrhage, pulmonary venous hypertension, ILD, and PAH. Based on the clinical course of these CHD-PAH in patients and the literature, CHD-PAH can occur with pulmonary vascular obstructive disease (PVOD)/pulmonary capillary hemangiomatosis (PCH), ILD, and/or alveolar hemorrhage. The severity of CHD-PAH may depend on a genetic disorder, respiratory infection, and upper airway stenosis. Additionally, pulmonary vasodilators may be involved in the development of PVOD/PCH and ILD. When patients with CHD-PAH show unexpected deterioration, clinicians should consider complications associated with PVOD/PCH and/or pulmonary disease. In addition, the choice of upfront combination therapy for pediatric patients with CHD-PAH should be selected carefully.

Identifying cardiogenic shock in the emergency department.

INTRODUCTION: Cardiogenic shock is difficult to diagnose due to diverse presentations, overlap with other shock states (i.e. sepsis), poorly understood pathophysiology, complex and multifactorial causes, and varied hemodynamic parameters. Despite advances in interventions, mortality in patients with cardiogenic shock remains high. Emergency clinicians must be ready to recognize and start appropriate therapy for cardiogenic shock early. OBJECTIVE: This review will discuss the clinical evaluation and diagnosis of cardiogenic shock in the emergency department with a focus on the emergency clinician. DISCUSSION: The most common cause of cardiogenic shock is a myocardial infarction, though many causes exist. It is classically diagnosed by invasive hemodynamic measures, but the diagnosis can be made in the emergency department by clinical evaluation, diagnostic studies, and ultrasound. Early recognition and stabilization improve morbidity and mortality. This review will focus on identification of cardiogenic shock through clinical examination, laboratory studies, and point-of-care ultrasound. CONCLUSIONS: The emergency clinician should use the clinical examination, laboratory studies, electrocardiogram, and point-of-care ultrasound to aid in the identification of cardiogenic shock. Cardiogenic shock has the potential for significant morbidity and mortality if not recognized early.

Validation of the diagnosis and triage algorithm for acute myocardial infarction in the setting of left bundle branch block.

BACKGROUND: Detecting acute ST-segment elevation myocardial infarction (STEMI) in the setting of left bundle branch block (LBBB) remains a challenge to clinicians. Several diagnostic and triage algorithms have been proposed to accurately identify LBBB patients with an acute culprit vessel. We aimed to validate the algorithm proposed by Cai et al., which uses patients' hemodynamic status and the modified Sgarbossa electrocardiography criteria to guide reperfusion therapy. METHODS: This retrospective study was performed with a chart review in emergency departments (EDs) of 2 medical centers, 2 regional hospitals, and 1 local hospital. From January 2010 to December 2014, 2432 consecutive patients were diagnosed as having STEMI in the ED, including 65 patients with LBBB (2.6%). RESULTS: The patients with LBBB were older and more frequently presented with acute pulmonary edema (58.5% vs 22.1%, p < 0.001), cardiogenic shock (16.9% vs 6.3% p = 0.006), and VT/VF episodes (7.7% vs 2.2%, p = 0.034) and had a higher 30-day mortality rate (20.0% vs 10.4% p = 0.032) than those without LBBB. We then tested the algorithm proposed by Cai et al. and noted a sensitivity of 93.8% in identifying a culprit lesion. CONCLUSIONS: The inconsistency of the guideline recommendations reflects the uncertainty of diagnostic and therapeutic strategies and the pressing need for tools to accurately identify the true acute myocardial infarction in patients presenting with chest pain and LBBB. The algorithm proposed by Cai et al. had good sensitivity and would allow emergency physicians to implement the timely treatment protocol for this high-risk population.