Pulmonary Ischemia Research Articles

Lung microvascular occlusion by platelet-rich neutrophil-platelet aggregates promotes cigarette smoke-induced severe flu.

Cigarette smoking is associated with a higher risk of ICU admissions among patients with flu. However, the etiological mechanism by which cigarette smoke (CS) exacerbates flu remains poorly understood. Here, we show that a mild dose of influenza A virus promotes a severe lung injury in mice preexposed to CS but not room air for 4 weeks. Real-time intravital (in vivo) lung imaging revealed that the development of acute severe respiratory dysfunction in CS- and flu-exposed mice was associated with the accumulation of platelet-rich neutrophil-platelet aggregates (NPAs) in the lung microcirculation within 2 days following flu infection. These platelet-rich NPAs formed in situ and grew larger over time to occlude the lung microvasculature, leading to the development of pulmonary ischemia followed by the infiltration of NPAs and vascular leakage into the alveolar air space. These findings suggest, for the first time to our knowledge, that an acute onset of platelet-driven thrombo-inflammatory response in the lung contributes to the development of CS-induced severe flu.

Concurrent Pulmonary Embolism and Acute Limb Ischemia Requiring Pulmonary Mechanical Thrombectomy and Initiation of Thrombolysis at the Index Operation

Concurrent Pulmonary Embolism and Acute Limb Ischemia Requiring Pulmonary Mechanical Thrombectomy and Initiation of Thrombolysis at the Index Operation

Review on the Method of Generating Vascular Cells from iPSCs and Its Application

Induced Pluripotent Stem Cells (iPSCs) embryonic-like stem cells are reprogrammed from skin or adult somatic cells. iPSC-derived cardiovascular cells have been widely used in many cardiovascular disease models and drug discovery. This paper reviews and summarizes the method of generating three different types of iPSC-derived cardiovascular cells, including iPSC-derived Endothelial Cells (ECs), Cardiomyocytes (CMs), and Vascular Smooth Muscle Cells (vSMCs), and the application of these iPSC-derived cardiovascular cells. The diseases discussed in this paper are pulmonary arterial hypertension (PAH) and critical limb ischemia (CLI). Additionally, construction of tissue-engineered blood vessels (TEBVs) for vascular grafting has also been discussed. To conclude, iPSCs, as a promising technique, is used in disease modeling, drug screening, tissue engineering, and the discovery of specific cardiovascular therapies for various patients.

Myeloid Progenitor Inhibitory Factor-1 (CCL23) Inhibits Lung Leukocyte Recruitment in a Primate Cardiopulmonary Bypass-Induced Pulmonary Ischaemia Model.

Bone marrow (BM)-derived polymorphonuclear leukocytes (PMNs) and monocytes (MO) induced by cardiopulmonary bypass (CPB) are highly proteolytic and cause postoperative lung injury. Although CCL23/Myeloid progenitor inhibitory factor-1 is a human CC chemokine with potent suppressor effects on myeloid progenitor cells, invivo inhibitory effects on BM-derived leukocyte kinetics associated with CPB are unknown. Two-hour CPB was surgically performed in cynomolgus monkeys and BM-derived leukocytes kinetics were monitored postoperatively by flow cytometry with 5'-bromo-2'-deoxyuridine (BrdU) and cytokine ELISA. Monkeys were given CCL23 (n=5) or saline (control, n=5) intravenously daily for 3 days before BrdU labelling and peripheral blood/bronchoalveolar lavage fluid (BALF) timepoint sampling to reveal BrdU-labelled cells. Levels of cytokines, CD11b, and L-selectin were considered leukocytic activation markers. The CCL23 treatment significantly prolonged BM transit of leukocytes (PMNs, 118.4±11.7-95.5±4.1 hours [control]; MO, 91.6±5.0-62.0±3.0 hours [control]) and reduced their alveolar appearance. The BM pool size of MO was decreased by CCL23 but PMNs were unaffected. CD11b, L-selectin expression of PMNs and MO during CPB, and post-surgical increases of interleukin (IL)-6, IL-8, TNF-α, MCP-1, and PMN elastase in the BALF were not suppressed. CCL23 treatment slows turnover of PMN and MO progenitors in BM and suppresses their circulatory release and lung recruitment. CCL23 has inhibitory effects specifically on the CPB-induced BM response and could hold value for preventing CPB-induced lung injury.

207: SEPTIC CHRONIC PULMONARY THROMBOEMBOLIC DISEASE RESCUED BY VA ECMO AND THROMBOENDARTERECTOMY

Introduction: We report the case of a man with chronic thromboembolic pulmonary hypertension (CTEPH) who developed mixed shock from a unique source and required veno-arterial extracorporeal membranous oxygenation (VA ECMO) for refractory cardiopulmonary failure. Description: A 19-year-old man with asthma and progressive dyspnea presented to an outside hospital after developing spontaneous pneumomediastinum. Computed tomography (CT) chest showed coarse calcifications in the right pulmonary artery (RPA) and lung nodules concerning for malignancy. Initial evaluation was consistent with CTEPH and antiphospholipid antibodies. PET scan and cardiac MRI confirmed thrombus. Endobronchial ultrasound (EBUS) and biopsy were then performed. The patient was transferred to our center for surgical pulmonary thromboendarterectomy (PTE). On hospital day (HD) 2, he acutely decompensated with tachycardia, hypoxemia, hypotension, and rigors. Broad-spectrum antibiotics, vasopressors, and non-invasive positive pressure ventilation (NIPPV) were started. He developed worsening hypoxemia and shock and was cannulated with VA ECMO, which rapidly improved his hemodynamics and oxygenation. He was quickly liberated from vasopressors and NIPPV. CT pulmonary angiography showed new foci of gas within the RPA clot, and blood cultures grew Streptococcus mitis and Granulicatella adiacens. Hypercoagulability evaluation revealed warm and cold agglutinins. After two sessions of plasmapheresis, he underwent PTE on HD 7. Purulence was noted around the RPA thrombus. Following successful PTE, he separated from cardiopulmonary bypass and ECMO. He liberated from vasopressors and inotropes and extubated on postoperative day (POD) 1. RPA fluid culture grew Actinomyces odontolyticus. He was discharged on POD 14. At 3-month follow-up, he had less dyspnea and no serious complications. Discussion: Patients with CTEPH have a high risk of acute right ventricular (RV) failure from worsening pulmonary hypertension or RV ischemia from systemic hypotension (e.g., sepsis). In this case, it is likely that biopsy of the RPA thrombus introduced bacteria, leading to bacteremia, septic shock and rapid hemodynamic collapse. VA ECMO was a successful rescue therapy, minimizing the need for escalating vasopressors and PPV, which may worsen RV dysfunction.

Priming of Cardiopulmonary Bypass with Human Albumin Decreases Endothelial Dysfunction after Pulmonary Ischemia-Reperfusion in an Animal Model.

The routine use of mechanical circulatory support during lung transplantation (LTx) is still controversial. The use of prophylactic human albumin (HA) or hypertonic sodium lactate (HSL) prime in mechanical circulatory support during LTx could prevent ischemia–reperfusion (IR) injuries and pulmonary endothelial dysfunction and thus prevent the development of pulmonary graft dysfunction. The objective was to investigate the impact of cardiopulmonary bypass (CPB) priming with HA and HSL compared to a CPB prime with Gelofusine (GF) on pulmonary endothelial dysfunction in a lung IR rat model. Rats were assigned to four groups: IR-CPB-GF group, IR-CPB-HA group, IR-CPB-HSL group and a sham group. The study of pulmonary vascular reactivity by wire myograph was the primary outcome. Glycocalyx degradation (syndecan-1 and heparan) was also assessed by ELISA and electron microscopy, systemic and pulmonary inflammation by ELISA (IL-1β, IL-10, and TNF-α) and immunohistochemistry. Clinical parameters were evaluated. We employed a CPB model with three different primings, permitting femoral–femoral assistance with left pulmonary hilum ischemia for IR. Pulmonary endothelium-dependent relaxation to acetylcholine was significantly decreased in the IR-CPB-GF group (11.9 ± 6.2%) compared to the IR-CPB-HA group (52.8 ± 5.2%, p < 0.0001), the IR-CPB-HSL group (57.7 ± 6.3%, p < 0.0001) and the sham group (80.8 ± 6.5%, p < 0.0001). We did not observe any difference between the groups concerning glycocalyx degradation, and systemic or tissular inflammation. The IR-CPB-HSL group needed more vascular filling and developed significantly more pulmonary edema than the IR-CPB-GF group and the IR-CPB-HA group. Using HA as a prime in CPB during Ltx could decrease pulmonary endothelial dysfunction’s IR-mediated effects. No effects of HA were found on inflammation.

ZNF354C Mediated by DNMT1 Ameliorates Lung Ischemia-Reperfusion Oxidative Stress Injury by Reducing TFPI Promoter Methylation to Upregulate TFPI.

Background Pulmonary ischemia reperfusion- (I/R-) induced dysfunction is a significant clinical problem after lung transplantation. In this study, we aim to explore the molecular mechanism of lung I/R injury (LIRI). Methods Bioinformatic analysis of gene involved in oxidative stress. A HUVEC oxygen glucose deprivation/reoxygenation (OGD/R) model and I/R mouse model were first established via I/R. The cellular proliferation, migration, reactive oxygen species (ROS), and parameters of lung injury were assessed via CCK-8, EdU staining, Transwell, cellular ROS kit, and H&E staining. We also confirmed related gene expressions and protein levels and the interaction between the tissue factor pathway inhibitor (TFPI) promotor and ZNF354C. Results Bioinformatic analysis results showed TFPI contributed to oxidative stress. OGD/R caused a reduction in cell viability and migration, hypermethylation of TFPI, increased ROS, and downregulation of ZNF354C, TFPI, and DNA methyltransferases (DNMTs) in HUVECs. Besides, ZNF354C could directly bind to the TFPI promoter, enhance proliferation and migration, and inhibit ROS in OGD/R-induced HUVECs by upregulating TFPI. More importantly, we discovered that 5-Aza could reduce TFPI methylation, upregulate TFPI, and enhance the binding of ZNF354C to the TFPI promoter in LIRI. Furthermore, DNMT1 silencing could induce proliferation and migration and prevent ROS in OGD/R-induced HUVECs by upregulating ZNF354C. Additionally, we verified that ZNF354C could alleviate LIRI by preventing DNA methylation in vivo. Conclusions ZNF354C overexpression induced proliferation and migration, as well as suppressed ROS in OGD/R-induced HUVECs, and alleviated LIRI in mice by inhibiting TFPI promoter methylation to upregulate TFPI. Therefore, ZNF354C and TFPI methylation might be promising molecular markers for LIRI therapy.

Protective effect of remote liver ischemic postconditioning on pulmonary ischemia and reperfusion injury in diabetic and non-diabetic rats.

Pulmonary ischemia and reperfusion (I/R) injury occurs in many clinical conditions and causes severe damage to the lungs. Diabetes mellitus (DM) predisposes to pulmonary I/R injury. We previously found that remote liver ischemia preconditioning protected lungs against pulmonary I/R injury. The aim of the present study was to investigate whether remote liver ischemic postconditioning (RLIPost) attenuates pulmonary damage induced by I/R injury in non-diabetic or diabetic rats. Male Sprague-Dawley rats were assigned into non-diabetic and diabetic groups. All rats except for the sham were exposed to 45 min of left hilum occlusion followed by 2 h of reperfusion. RLIPost was conducted at the onset of pulmonary reperfusion by four cycles of 5 min of liver ischemia and reperfusion. Lung injury was assessed by the wet/dry weight ratio, pulmonary oxygenation, histopathological changes, apoptosis and the expression of inflammatory cytokines. Reperfusion-associated protein phosphorylation states were determined. RLIPost offered strong pulmonary-protection in both non-diabetic and diabetic rats, as reflected in reduced water content and pulmonary structural damage, recovery of lung function, inhibition of apoptosis and inflammation after ischemia-reperfusion. RLIPost induced the activation of pulmonary STAT-3, a key component in the SAFE pathway, but not activation of the proteins in the RISK pathway, in non-diabetic rats. In contrast, RLIPost-induced pulmonary protection in diabetic lungs was independent of SAFE or RISK pathway activation. These results demonstrate that RLIPost exerts pulmonary protection against I/R-induced lung injury in non-diabetic and diabetic rats. The underlying mechanism for protection may be different in non-diabetic (STAT-3 dependent) versus diabetic (STAT-3 independent) rats.

Review of Mesenteric Ischemia in COVID-19 Patients.

The new coronavirus (COVID-19) infection, first detected in Wuhan, China in 2019 has become a pandemic that has spread to nearly every country in the world. Through October 11, 2021, more than 23 billion confirmed cases and 4.8 million fatalities were reported globally. The bulk of individuals afflicted in India during the first wave were elderly persons. The second wave, however, resulted in more severe diseases and mortality in even younger age groups due to mutations in the wild virus. Symptoms may range from being asymptomatic to fatal acute respiratory distress syndrome (ARDS). In addition to respiratory symptoms, patients may present with gastrointestinal symptoms such as stomach pain, vomiting, loose stools, or mesenteric vein thrombosis. The frequency of patients presenting with thromboembolic symptoms has recently increased. According to certain studies, the prevalence of venous thromboembolism among hospitalized patients ranges from 9 to 25%. It was also shown that the incidence is significantly greater among critically sick patients, with a prevalence of 21–31%. Although the exact origin of thromboembolism is unknown, it is considered to be produced by several altered pathways that manifest as pulmonary embolism, myocardial infarction, stroke, limb gangrene, and acute mesenteric ischemia. Acute mesenteric ischemia (AMI) is becoming an increasingly prevalent cause of acute surgical abdomen in both intensive care unit (ICU) and emergency room (ER) patients. Mesenteric ischemia should be evaluated in situations with unexplained stomach discomfort. In suspected situations, appropriate imaging techniques and early intervention, either non-surgical or surgical, are necessary to avert mortality. The purpose of this article is to look at the data on acute mesenteric ischemia in people infected with COVID-19.

Uterine Necrosis After Uterine Artery Embolization (UAE) - Rare Entity with a Dilemma

ABSTRACT Uterine artery embolization (UAE), a minimally invasive procedure used for controlling and managing profuse bleeding in conditions like uterine fibroids, and uterine hemorrhage, in cases of intractable postpartum hemorrhage (PPH). A wide array of complications due to UAE includes pulmonary embolism, uterine ischemia, necrosis, sepsis, and death. A 27 years old married woman (parity 1+2) presented with complaints of a mass protruding of the vagina with dirty brown vaginal discharge. Following UAE was done for postpartum hemorrhage (PPH) she had developed fever and burning micturition on which ultrasound was done to show an anteverted, enlarged, bulky uterus, with multiple endogenic foci, with endometrial canal and adjacent myometrium suggestive of infective pathology. In this case report complications of UAE for the management of PPH were discussed, however, research is required to comprehend the causes of uterine necrosis following uterine artery embolization and its management. Keywords: Uterine Artery Embolization; Postpartum Hemorrhage; Uterine Necrosis; Pathology.

Analysis and Discussion Concerning Death

The analysis and discussion concerning death as intended by the Researcher depicts that death is an irreversible condition or state encountered by beings (all living creatures), due to a total dysfunction of the body organs. Such an irreversible condition is an enemy of human beings, which supersedes humanity, causing unexpected changes in life. It came as a punishment of abusing the supernatural power and finally it became a fact of not living forever. By the use of different literatures, Interviews and Documents, the research explored diverse concerns of death and drew its conclusion. Some of those concerns are “how is death detected? What are the causatives of death? Does death have its remedy? Where are dead people? Why do we bury the dead? And what is next after death?” The findings reveal that Doctors prove death by assessing and measuring the vital signs such as Blood Pressure, Pulse Rate, Respiratory Rate and Body Temperature. Moreover, the causatives of death include chronic pulmonary obstructive disease, ischemia, stroke, dehydration, infections and pain as well as old age. Those who encounter death are laid in the graves because God commanded it to be so and they produce unpleasant smell and stink. The remedy of it depends on the supernatural power that is believed to have ability of restoring the lost lives at consummation. That’s why Christians believe that on the second coming of Jesus Christ, all the dead shall rise. Hence, human beings have to be kin enough in lifetime, so that they may prolong a bit their lifespan through observance of health principles and guidelines.

An Update on COVID-19 Vaccine Induced Thrombotic Thrombocytopenia Syndrome and Some Management Recommendations.

The thrombotic thrombocytopenia syndrome (TTS), a complication of COVID-19 vaccines, involves thrombosis (often cerebral venous sinus thrombosis) and thrombocytopenia with occasional pulmonary embolism and arterial ischemia. TTS appears to mostly affect females aged between 20 and 50 years old, with no predisposing risk factors conclusively identified so far. Cases are characterized by thrombocytopenia, higher levels of D-dimers than commonly observed in venous thromboembolic events, inexplicably low fibrinogen levels and worsening thrombosis. Hyper fibrinolysis associated with bleeding can also occur. Antibodies that bind platelet factor 4, similar to those associated with heparin-induced thrombocytopenia, have also been identified but in the absence of patient exposure to heparin treatment. A number of countries have now suspended the use of adenovirus-vectored vaccines for younger individuals. The prevailing opinion of most experts is that the risk of developing COVID-19 disease, including thrombosis, far exceeds the extremely low risk of TTS associated with highly efficacious vaccines. Mass vaccination should continue but with caution. Vaccines that are more likely to cause TTS (e.g., Vaxzevria manufactured by AstraZeneca) should be avoided in younger patients for whom an alternative vaccine is available.

Coronavirus disease 2019-associated pulmonary fibrosis: clinical findings, pathogenesis, and potential treatment.

Coronavirus disease 2019-associated pulmonary fibrosis: clinical findings, pathogenesis, and potential treatment.

POS-751 AN UNUSUAL PRESENTATION OF ARTERI-VENOUS FISTULA AFTER RENAL BIOPSY: CASE REPORT

Renal biopsy is an important diagnostic procedure but is associated with a number of significant complications even when performed by a skilled operator. While most of these complications present with haemodynamic disturbance, pain or macroscopic haematuria, some – such as the development of a post-biopsy arteriovenous fistula may be occult. We present an unusual presentation of a post-biopsy arteriovenous fistula which was diagnosed after the patient reported an audible bruit. A 39-year-old woman with end stage renal disease of unknown etiology received her first kidney transplant in February 2020. The right kidney from a deceased after cardiac death donor was transplanted into her right iliac fossa. Before transplantation, she had been on hemodialysis via an arteriovenous fistula (AVF) for a year. There was delayed graft function and the patient was dialysed through her AVF on the 2nd day of transplantation. Graft function was slow to improve and a kidney biopsy was performed on the 6th day post-transplantation. The biopsy was performed under ultrasound (US)control with two passes of a 16 G needle. Post-procedure observations were unremarkable and the patient went home after 6 hours of bed rest.The biopsy showed borderline rejection and the patient was prescribedthree doses of intravenous methylprednisolone. On the second day post-biopsy, graft function remained poor and routine bloods showed a drop in haemoglobin from 107 to 78 g/L. Abdominal US did not show any abnormality. Patient received blood transfusion and was observed overnight. The patient was discharged home next day. On the 5th day post-biopsy, the patient presented with reports of hearing “buzzing” sounds. ENT review was unremarkable. Graft function was poor and the patient remained on dialysis. Abdominal US and Doppler studies showed a large AVF within the transplanted kidney at the site of the earlier biopsy (fig 1). Figure 1: Doppler ultrasound of renal transplant showing post biopsy AVF The fistula was large and, with evidence of recent bleeding, thus underwent coil embolisation in the interventional radiology department (fig 2). Figure 2: Coil embolisation of AVF. Left panel shows initial angiographic appearance; right panel shows appearance following coil embolisation At present, the patient is nine months post-transplantation and remains dialysis independent with stable graft function and an eGFR 25-30 mL/min/1.73m2. Most biopsy-associated AVFs close spontaneously, are asymptomatic, and do not require intervention. The indication for intervention is usually an increase in the size of fistula over time, the development of signs of heart failure, deterioration in kidney function, or a rise in blood pressure. Embolisation of biopsy-associated AVFs has been reported to result in good outcomes with minimal changes in serum creatinine and estimated glomerular filtration rate. The risks include proximal dissemination of the embolisation material and the resultant focal occlusion of the arterial system causing renal, gut and pulmonary ischaemia. Surgical procedures are reserved for large AVFs with high velocity flows. Complications of kidney biopsy can be asymptomatic, and missed because of late and atypical presentation. A possibility of kidney biopsy related complication should always be considered when a patient presents within few weeks of the kidney biopsy.

Cardiopulmonary bypass increases endothelial dysfunction after pulmonary ischaemia-reperfusion in an animal model.

Endothelial dysfunction during ischaemia-reperfusion (IR) is a major cause of primary graft dysfunction during lung transplantation. The routine use of cardiopulmonary bypass (CPB) during lung transplantation remains controversial. However, the contribution of CPB to pulmonary endothelial dysfunction remains unclear. The objective was to investigate the impact of CPB on endothelial dysfunction in a lung IR rat model. Rats were allocated to 4 groups: (i) Sham, (ii) IR, (iii) CPB and (iv) IR-CPB. The primary outcome was the study of pulmonary vascular reactivity by wire myograph. We also assessed glycocalyx degradation by enzyme-linked immunosorbent assay and electron microscopy and both systemic and pulmonary inflammation by enzyme-linked immunosorbent assay and immunohistochemistry. Rats were exposed to 45 min of CPB and IR. We used a CPB model allowing femoro-femoral support with left pulmonary hilum ischaemia for IR. Pulmonary endothelium-dependent relaxation to acetylcholine was markedly reduced in the IR-CPB group (10.7 ± 9.1%) compared to the IR group (50.5 ± 5.2%, P < 0.001), the CPB group (54.1 ± 4.7%, P < 0.001) and the sham group (80.8 ± 6.7%, P < 0.001), suggesting that the association of pulmonary IR and CPB increases endothelial dysfunction. In IR-CPB, IR and CPB groups, vasorelaxation was completely abolished when inhibiting nitric oxide synthase, suggesting that this relaxation process was mainly mediated by nitric oxide. We observed higher syndecan-1 plasma levels in the IR-CPB group in comparison with the other groups, reflecting an increased degradation of glycocalyx. We also observed higher systemic inflammation in the IR-CPB group as shown by the increased plasma levels of IL-1β, IL-10. CPB significantly increased the IR-mediated effects on pulmonary endothelial dysfunction. Therefore, the use of CPB during lung transplantation could be deleterious, by increasing endothelial dysfunction.

Integrin αIIbβ3 Regulates Platelet-Procoagulant Activity in the Lung

Pulmonary thrombosis is a major complication associated with high morbidity. Despite advances in diagnosis and treatment, the pathophysiology of pulmonary thrombosis remains incompletely understood. New clinical evidence suggests that in situ platelet activation resulting in enhanced procoagulant activity may promote pulmonary thrombosis. Improved understanding of the etiological mechanism would enable the development of new therapies for pulmonary thrombosis. Collagen and thromboplastin (TF) were administered intravascularly (IV) to C57BL/6 (WT) mice and the pulmonary microcirculation was visualized using quantitative fluorescence intravital fluorescence lung microscopy (qFILM). Fluorochrome-conjugated anti-mouse CD49b Ab and dextran was administered IV for in vivo staining of circulating platelets and visualization of blood vessels, respectively. Pulmonary thrombosis was defined as occlusion of blood vessels with platelet aggregates leading to pulmonary ischemia. Additionally, quantitative microfluidic fluorescence microscopy (qMFM) was used to study the effect of platelet αIIbβ3 inhibition on platelet procoagulant activity in human blood under vascular mimetic flow conditions. Collagen and TF triggered dose-dependent pulmonary thrombosis in mice in vivo, which involved development of platelet-rich thrombi in the pulmonary arteriolar bottlenecks (junction of pulmonary arteriole and capillaries), resulting in a transient ischemia in the arteriole and the down-stream capillary tree. The pulmonary arteriole thrombosis triggered by IV collagen or TF was protracted, lethal and completely abrogated following IV administration of αIIbβ3 receptor inhibitor (eptifibatide). Inhibition of platelet αIIbβ3 also significantly reduced platelet procoagulant activity, fibrin formation and thrombus formation in human blood flowing through microfluidic channels ex vivo. Our current findings suggest that αIIbβ3-dependent platelet procoagulant activity promotes pulmonary thrombosis. Both our models have potential application in investigating the molecular determinants of pulmonary thrombosis in diverse pulmonary disorders as well as evaluating efficacy of new antithrombotic drugs. Disclosures No relevant conflicts of interest to declare.

Pulmonary ischaemia without pulmonary arterial thrombus in COVID-19 patients receiving extracorporeal membrane oxygenation: a cohort study

AIMTo evaluate the incidence of pulmonary ischaemia in COVID-19 patients on extracorporeal membrane oxygenation (ECMO), and its correlation with pulmonary artery thrombosis.MATERIALS AND METHODSComputed tomography (CT) thorax of all patients receiving ECMO with proven COVID-19 pneumonitis between March and May 2020 were analysed for the presence and extension of pulmonary thromboembolic disease.RESULTSFifty-one patients were reviewed. The mean (range) age of 45 (26–66) years; 38/51 (74.5%) were men. All patients had severe COVID-19 pneumonitis, and 18/51 (35.3%) had macroscopic thrombosis (15 with associated ischaemia); however, 13/51 (25.5%) patients had ischaemia without associated thrombus.CONCLUSIONThe majority of patients with COVID-19 who received ECMO had areas of ischaemia within consolidated lungs, almost half of these without subtending pulmonary artery thrombosis. Although the prognostic significance of these findings is unclear, they are highly suggestive of lung ischaemia due to isolated microvascular immune thrombosis.

Efficaciousness of Low Affinity Compared to High Affinity TSPO Ligands in the Inhibition of Hypoxic Mitochondrial Cellular Damage Induced by Cobalt Chloride in Human Lung H1299 Cells.

The 18 kDa translocator protein (TSPO) plays an important role in apoptotic cell death, including apoptosis induced by the hypoxia mimicking agent cobalt chloride (CoCl2). In this study, the protective effects of a high (CB86; Ki = 1.6 nM) and a low (CB204; Ki = 117.7 nM) affinity TSPO ligands were investigated in H1299 lung cancer cell line exposed to CoCl2. The lung cell line H1299 was chosen in the present study since they express TSPO and able to undergo programmed cell death. The examined cell death markers included: ATP synthase reversal, reactive oxygen species (ROS) generation, mitochondrial membrane potential (Δψm) depolarization, cellular toxicity, and cellular viability. Pretreatment of the cells with the low affinity ligand CB204 at a concentration of 100 µM suppressed significantly (p < 0.05 for all) CoCl2-induced cellular cytotoxicity (100%), ATP synthase reversal (67%), ROS generation (82%), Δψm depolarization (100%), reduction in cellular density (97%), and also increased cell viability (85%). Furthermore, the low affinity TSPO ligand CB204, was harmless when given by itself at 100 µM. In contrast, the high affinity ligand (CB86) was significantly effective only in the prevention of CoCl2–induced ROS generation (39%, p < 0.001), and showed significant cytotoxic effects when given alone at 100 µM, as reflected in alterations in ADP/ATP ratio, oxidative stress, mitochondrial membrane potential depolarization and cell death. It appears that similar to previous studies on brain-derived cells, the relatively low affinity for the TSPO target enhances the potency of TSPO ligands in the protection from hypoxic cell death. Moreover, the high affinity TSPO ligand CB86, but not the low affinity ligand CB204, was lethal to the lung cells at high concentration (100 µM). The low affinity TSPO ligand CB204 may be a candidate for the treatment of pulmonary diseases related to hypoxia, such as pulmonary ischemia and chronic obstructive pulmonary disease COPD.

Behavioral Status in Rats with Experimental Comorbidity of Chronic Obstructive Pulmonary Disease and Acute Cerebral Ischemia

Objectives. To undertake a comparative analysis of the behavioral patterns of rats with experimental chronic obstructive pulmonary disease (COPD), acute cerebral ischemia (ACI), and the combination of these pathologies. Materials and methods. The study was performed on 70 male Wistar laboratory rats weighing 250–300 g, divided into five groups. The results of comparative evaluation of the neurological and behavioral status of the rats is presented. Experimental COPD was modeled using combined inducers (purified papain and bacterial lipopolysaccharide) and ACI by simultaneous bilateral occlusion of the common carotid arteries. Neurological status was evaluated using the NSS scale and behavioral status using a battery of tests: the open field test, the eight-arm radial maze, and the elevated O maze. Results and conclusions. Animals with combined pathologies showed the lowest level (20%) of survival and the greatest severity of neurological and behavioral disorders. These animals were characterized by sharp restriction to locomotor and exploratory activity, high anxiety, and increasing autonomic imbalance. Survival in rats with ACI only was 35%, while abnormalities in their neurological and behavioral status were of moderate severity. Rats with experimental COPD only had mild neurological deficit. Behavioral abnormalities consisted of moderate restriction to locomotor function and minor increases in anxiety on the background of retained exploratory activity and spatial memory. The results provide evidence of the relevance of the model of respiratory and cerebrovascular comorbidity for assessment of changes in physiological functions and their subsequent treatment.

Endovascular repair of ruptured abdominal aortic aneurysm is superior to open repair: Propensity-matched analysis in the Vascular Quality Initiative

ObjectiveThe few randomized trials comparing endovascular with open surgical repair of ruptured abdominal aortic aneurysm (rAAA) were poorly designed and heavily criticized. The short-term and midterm survival advantages of endovascular repair remain unclear. We sought to compare the two treatment modalities using a propensity-matched analysis in a real-world setting. MethodsAll ruptured cases of open surgical repair (rOSR) and endovascular aneurysm repair (rEVAR) in the Vascular Quality Initiative were analyzed (2003-2018). Raw and propensity-matched rEVAR and rOSR cohorts were compared. Primary and secondary outcomes included postoperative major adverse events (cardiovascular, pulmonary, renal, bowel or limb ischemia, reoperation) and 30-day and 1-year mortality. Univariate, multivariate, and Kaplan-Meier analyses were performed. ResultsThere were 4929 rAAA repairs performed, 2749 rEVAR and 2180 rOSR. Compared with rEVAR patients, rOSR patients had higher rates of myocardial ischemic events (15% vs 10%; P < .001), major adverse events (67% vs 37%; P < .001), and 30-day death (34% vs 21%; P < .001). On adjusted analysis, rOSR was predictive of 30-day mortality (odds ratio, 1.8; 95% confidence interval, 1.5-2.2). After 1:1 matching, the study cohort consisted of 724 pairs of rOSR and rEVAR. The rOSR patients had twice the length of stay (median, 10 days [interquartile range, 5-19 days] vs 5 days [interquartile range, 3-10 days]; P < .001). Univariate analysis demonstrated persistent increased 30-day mortality after rOSR (32% vs 18%; P < .001) and higher rates of myocardial infarction (14% rOSR vs 8% rEVAR; P = .002), respiratory complications (38% vs 20%; P < .001), and acute kidney injury (42% vs 26%; P < .001). Overall major adverse event rate was higher after rOSR (68% vs 35%; P < .001). Multivariable regression analysis of the propensity-matched pairs demonstrated that rOSR was associated with double the 30-day mortality compared with rEVAR (odds ratio, 2.0; 95% confidence interval, 1.6-2.7). All-cause 1-year survival was 73% and 59% after rEVAR and rOSR in the propensity-matched cohort, respectively (P < .001). ConclusionsThis is one of the largest studies of rAAA demonstrating clear short-term and midterm survival benefits of rEVAR over rOSR that persisted after matching on all major demographic, comorbid, and anatomic variables. Furthermore, patients who survived rOSR had twice the length of stay with increased rates of complications compared with rEVAR patients. These data suggest a more aggressive endovascular approach for rAAA in patients with suitable anatomy.