Systemic Arterial Circulation Research Articles

Steady Flow Left Ventricle Unloading Is Superior to Pulsatile Pressure Augmentation Venting During Venoarterial Extracorporeal Membrane Oxygenation Support.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) shunts venous blood to the systemic arterial circulation to provide end-organ perfusion while increasing afterload that may impede left ventricle (LV) ejection and impair cardiac recovery. To maintain flow across the aortic valve and reduce risk of lethal clot formation, secondary mechanical circulatory support (MCS) devices are increasingly used despite limited understanding of their effects on cardiac function. This study sought to quantify the effects of VA-ECMO and combined with either intraaortic balloon pump (IABP) or percutaneous ventricular assist device (pVAD) on LV physiologic state and perfusion metrics in a porcine model of acute cardiogenic shock. Shock was induced through serial left anterior descending artery microbead embolization followed by initiation of VA-ECMO support and then placement of either IABP or pVAD. Hemodynamic measurements, LV pressure-volume loops, and carotid artery blood flow were evaluated before and after institution of combined MCS. The IABP decreased LV end-diastolic pressure by a peak of 15% while slightly increasing LV stroke work compared with decreases of more than 60% and 50% with the pVAD, respectively. The pVAD also demonstrated increased coronary perfusion and systemic pressure gradients in comparison to the IABP. Combined support with VA-ECMO and pVAD improves cardiovascular state in comparison to IABP.

Decompression illness: a comprehensive overview.

Decompression illness is a collective term for two maladies (decompression sickness [DCS] and arterial gas embolism [AGE]) that may arise during or after surfacing from compressed gas diving. Bubbles are the presumed primary vector of injury in both disorders, but the respective sources of bubbles are distinct. In DCS bubbles form primarily from inert gas that becomes dissolved in tissues over the course of a compressed gas dive. During and after ascent ('decompression'), if the pressure of this dissolved gas exceeds ambient pressure small bubbles may form in the extravascular space or in tissue blood vessels, thereafter passing into the venous circulation. In AGE, if compressed gas is trapped in the lungs during ascent, pulmonary barotrauma may introduce bubbles directly into the pulmonary veins and thence to the systemic arterial circulation. In both settings, bubbles may provoke ischaemic, inflammatory, and mechanical injury to tissues and their associated microcirculation. While AGE typically presents with stroke-like manifestations referrable to cerebral involvement, DCS can affect many organs including the brain, spinal cord, inner ear, musculoskeletal tissue, cardiopulmonary system and skin, and potential symptoms are protean in both nature and severity. This comprehensive overview addresses the pathophysiology, manifestations, prevention and treatment of both disorders.

Decompression illness: a comprehensive overview

Decompression illness is a collective term for two maladies (decompression sickness [DCS] and arterial gas embolism [AGE]) that may arise during or after surfacing from compressed gas diving. Bubbles are the presumed primary vector of injury in both disorders, but the respective sources of bubbles are distinct. In DCS bubbles form primarily from inert gas that becomes dissolved in tissues over the course of a compressed gas dive. During and after ascent (‘decompression’), if the pressure of this dissolved gas exceeds ambient pressure small bubbles may form in the extravascular space or in tissue blood vessels, thereafter passing into the venous circulation. In AGE, if compressed gas is trapped in the lungs during ascent, pulmonary barotrauma may introduce bubbles directly into the pulmonary veins and thence to the systemic arterial circulation. In both settings, bubbles may provoke ischaemic, inflammatory, and mechanical injury to tissues and their associated microcirculation. While AGE typically presents with stroke-like manifestations referrable to cerebral involvement, DCS can affect many organs including the brain, spinal cord, inner ear, musculoskeletal tissue, cardiopulmonary system and skin, and potential symptoms are protean in both nature and severity. This comprehensive overview addresses the pathophysiology, manifestations, prevention and treatment of both disorders.

Bilateral Pulmonary Sequestration – A Rare Entity

Abstract Bronchopulmonary sequestration (BPS) is a congenital anomaly within the spectrum of abnormalities that can affect the normal development of airways, lung parenchyma, and vasculature. It accounts for up to 6.4% of all congenital pulmonary malformations. Sequestrated lung is a nonfunctioning mass of lung tissue that lacks communication with the tracheobronchial tree and is supplied by systemic arterial circulation. Pulmonary sequestration is usually a unilateral disease, bilateral pulmonary sequestration is a rare entity. Herein we present the case of a 26year old female, evaluated for cough with expectoration, hemoptysis and loss of weight, whose radiology suggestive of bilateral bronchopulmonary sequestration.

Factors associated with thrombotic disease in dogs with renal proteinuria: A retrospective of 150 cases.

Knowledge of additional risk factors for thrombotic disease (TD) among dogs with renal proteinuria is limited; these might differ for TD affecting the systemic arterial (AT), systemic venous (VT), and pulmonary circulation (PT). To compare signalment and clinicopathological data between dogs with renal proteinuria with or without TD, and between dogs with AT, VT, and PT. One hundred fifty client-owned dogs with renal proteinuria, 50 of which had TD. Retrospective case-controlled study. A database search (2004-2021) identified proteinuric dogs (UPC > 2) with and without TD. Clinicopathological data were obtained from the records. TD and non-TD (NTD) groups were compared by binary logistic regression, and AT, VT, and PT groups by multinomial regression. Normal data presented as mean ± SD, non-normal data presented as median [25th, 75th percentiles]. Cavalier King Charles Spaniels were overrepresented in the TD group (OR = 98.8, 95% CI 2.09-4671, P = .02). Compared to NTD cases, TD cases had higher concentration of neutrophils (11.06 [8.92, 16.58] × 109 /L vs 7.31 [5.63, 11.06] × 109 /L, P = .02), and lower concentration of eosinophils (0 [0, 0.21] × 109 /L vs 0.17 [0.04, 0.41] × 109 /L, P = .002) in blood, and lower serum albumin (2.45 ± 0.73 g/dL vs 2.83 ± 0.73 g/dL, P = .04). AT cases had higher serum albumin concentrations than VT cases (2.73 ± 0.48 g/dL vs 2.17 ± 0.49 g/dL, P = .03) and were older than PT cases (10.6 ± 2.6 years vs 7.0 ± 4.3 years, P = .008). VT cases were older (9.1 ± 4.2 years vs 7.0 ± 4.3 years, P = .008) and had higher serum cholesterol concentration (398 [309-692 mg/dL] vs 255 [155-402 mg/dL], P = .03) than PT cases. Differences between thrombus locations could reflect differences in pathogenesis.

Cerebral blood flow dependency on systemic arterial circulation in progressive multiple sclerosis

Background: Cerebrovascular reactivity (CVR) is a regulatory mechanism responsible for redistributing cerebral blood flow based on vasoactive stimuli and fluctuations in metabolic demand. Under normal conditions and proper functioning of the neurovascular unit, a direct association between cerebral arterial blood flow and systemic arterial blood flow (SABF) is not expected. Previous studies have suggested impairment of CVR in multiple sclerosis (MS).1 Moreover, lower cerebral perfusion in MS has been linked with greater neuronal pathology and worse disability outcomes.2,3
 Objectives: To determine the relationship between SABF and cerebral perfusion measures in MS patients.
 Мaterials and methods: Cerebral perfusion and SABF were assessed in 118 patients (75 clinically isolated syndrome (CIS)/relapsing-remitting MS and 43 progressive MS) through magnetic resonance imaging (MRI) examination with dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) and Doppler ultrasound, respectively. Measures of mean transit time (MTT) and time-to-peak (TTP), measured in seconds, of the normal-appearing whole brain (NAWB) and gray matter (GM) were calculated. Blood flow through the bilateral common carotid and vertebral arteries (in mL/min) represents the SABF. Whole brain volume (WBV) and body mass index (BMI) were used as additional covariates.
 Results: Higher systolic blood pressure was associated with lower SABF (-0.256, p=0.006). In the total MS sample, higher SABF was associated with shorter MTT and TTP of the NAWB (r=-0.256, p=0.007 and r=-0.307, p=0.001) and GM (r=-0.239, p=0.012 and r=-0.3, p=0.001). The SABF and TTP associations were driven by the progressive multiple sclerosis (PMS) patients (r=-0.451, p=0.004 and r=-0.451, p=0.011). Only in PMS, SABF remained a significant predictor of NAWB (standardized β=-0.394, p=0.022) and GM TTP (standardized β=-0.351, p=0.037). MTT and TTP were significantly lower in patients within lower SABF quartiles when compared to the higher quartiles (age, sex, BMI and WBV-adjusted ANCOVA p<0.025). (Figure 1) The differences in PWI-based measured remained significant after additional correction for the prevalence of hypertension. Although statistically non-significant, PMS patients within the lower SABF quartiles had a numerically greater disability (expanded disability status scale scores of 5.9 vs 5.0 for Q1 and Q4), (multiple sclerosis severity score of 5.8 vs 3.8), slower walking as measured by timed 25-foot walk test (23.9 s vs 15.8 s) and worse hand dexterity as measured by 9-hole peg test (50.8 s vs. 29.3 s).
 Conclusions: The direct relationship between systemic and cerebral blood flow seen in PMS patients may suggest a failure in cerebrovascular reactivity mechanisms and insufficient perfusion control. Cerebral blood flow in PMS may be increasingly dependent on the SABF.

Cerebral blood flow dependency on systemic arterial circulation in progressive multiple sclerosis.

To determine the relationship between systemic arterial blood flow (SABF) and cerebral perfusion measures in multiple sclerosis (MS) patients. Cerebral perfusion and SABF were assessed in 118 patients (75 clinically isolated syndrome (CIS)/relapsing-remitting MS and 43 progressive MS) through MRI examination with dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) and Doppler ultrasound, respectively. Measures of mean transit time (MTT) and time-to-peak (TTP), measured in seconds, of the normal-appearing whole brain (NAWB) and gray matter (GM) were calculated. Blood flow through the bilateral common carotid and vertebral arteries (in mL/min) represents the SABF. Whole brain volume (WBV) and body mass index (BMI) were used as additional covariates. Higher systolic blood pressure was associated with lower SABF (-0.256, p = 0.006). In the total MS sample, higher SABF was associated with shorter MTT and TTP of the NAWB (r = -0.256, p = 0.007 and r = -0.307, p = 0.001) and GM (r = -0.239, p = 0.012 and r = -0.3, p = 0.001). The SABF and TTP associations were driven by the PMS patients (r = -0.451, p = 0.004 and r = -0.451, p = 0.011). Only in PMS, SABF remained a significant predictor of NAWB (standardized β = -0.394, p = 0.022) and GM TTP (standardized β = -0.351, p = 0.037). MTT and TTP were significantly lower in patients within lower SABF quartiles when compared to the higher quartiles (age-, sex-, BMI-, and WBV-adjusted ANCOVA p < 0.025). The direct relationship between systemic and cerebral blood flow seen in PMS patients may suggest failure in cerebrovascular reactivity mechanisms and insufficient perfusion control. Cerebral blood flow in PMS may be increasingly dependent on the SABF. • In progressive multiple sclerosis (MS) patients, the systemic arterial blood flow (SABF) is associated with perfusion-based measure of time-to-peak (TTP) of the normal-appearing whole brain (r = -0.451, p = 0.004) and gray matter (r = -0.451, p = 0.004). • Cerebral blood flow in progressive MS is directly dependent on systemic arterial blood flow and may be influenced by blood pressure changes. • Neurovascular unit impairment may play an important role in MS pathophysiology and contribute towards greater clinical disability.

Unusual cause of dyspnea and hemoptysis in a healthy female

Rare congenital malformation can lead to the aberrant communication between systemic arterial circulation with pulmonary venous circulation which can range from sequestration to arteriovenous fistulas. We describe a 24 year old female with no significant medical history presenting with dyspnea and hemoptysis. On Computerized Tomography (CT) and angiogram found to have an aberrant vessel branching from celiac axis supplying the right lower lobe and draining into the inferior pulmonary vein with evidence of vascular steal. Due to the size of the vessel, decision was made to forego coil embolization and underwent Video-Assisted Thoracoscopic Surgery (VATS) ligation of the aberrant vessel. She had an uncomplicated operative course and post operatively had resolution of her symptoms. This report demonstrates a rare anatomical congenital vascular malformation causing hemoptysis and resolution of symptoms after ligation of the aberrant blood vessel. Keywords: pulmonary arteriovenous fistula; vats; hemoptysis.

Impedance of the Systemic and Pulmonary Arterial Circulations by Cardiac Magnetic Resonance

In normal conditions, impedance of the pulmonary circulation (PA-Zc) is one-third lower than the systemic circulation (Ao-Zc) with ventricular function coupled to the arterial circulation by relative matching between contractility and afterload. Simultaneous measurement of Ao-Zc and PA-Zc using a cardiac magnetic resonance (CMR) technique has not previously been performed.

Intracranial Hemorrhage Associated with Therapeutic Anticoagulation in Three Critically Ill COVID-19 Patients: A Case Series

Introduction: The COVID-19 pandemic has challenged global health with novel pathogenesis that is both severe and poorly understood. Several mechanisms have been proposed to explain the severity and complexity of the clinical illness including cytokine storm release, thromboembolic microangiopathy, direct cytotoxicity, and post-viral bacterial super infection. Cases: The patients in this case series were all admitted to the intensive care unit with respiratory failure from COVID-19 requiring invasive mechanical ventilation. They were all started on anticoagulation. All three patients developed acute kidney injuries. The first patient had hypertensive emergency at the time of the bleed. The second and third patient both had supratherapeutic heparin levels at the time of the bleed. Methods: We followed patients aged 18 years and above who were admitted to the ICU for COVID-19 during April and May 2020. We then followed those who required therapeutic anticoagulation for any indication and evaluated the ones that developed ICH. Results: Out of the 79 patients admitted to the ICU for COVID-19 related illness during April and May 2020, 31 were placed on therapeutic anticoagulation (intermediate or full-dose) for indications that included hypercoagulable state, ACS, atrial fibrillation, and deep vein thrombosis. 25% of patients on anticoagulation developed bleeding for which the anticoagulation had to be stopped. Three out of these 31 patients developed ICH while on anticoagulation, accounting for 3.8% of our ICU population with COVID-19 Discussion: Activation of coagulation pathways during cytokine storms can result in systemic thromboembolism, in both venous and arterial circulations posing risk of ischemic infarctions to any organ. Supratherapeutic heparin levels and acute kidney injuries are common in COVID-19 patients. The ideal candidates for anticoagulation, the recommended agent and dose, and duration of treatment remain unclear. Conclusion: The benefits of anticoagulation should be weighed against the potential risk of bleeding.

Systems analysis of the mechanisms governing the cardiovascular response to changes in posture and in peripheral demand during exercise

Blood flows and pressures throughout the human cardiovascular system are regulated in response to various dynamic perturbations, such as changes to peripheral demands in exercise, rapid changes in posture, or loss of blood from hemorrhage, via the coordinated action of the heart, the vasculature, and autonomic reflexes. To assess how the systemic and pulmonary arterial and venous circulation, the heart, and the baroreflex work together to effect the whole-body responses to these perturbations, we integrated an anatomically-based large-vessel arterial tree model with the TriSeg heart model, models capturing nonlinear characteristics of the large and small veins, and baroreflex-mediated regulation of vascular tone and cardiac chronotropy and inotropy. The model was identified by matching data from the Valsalva maneuver (VM), exercise, and head-up tilt (HUT). Thirty-one parameters were optimized using a custom parameter-fitting tool chain, resulting in an unique, high-fidelity whole-body human cardiovascular systems model. Because the model captures the effects of exercise and posture changes, it can be used to simulate numerous clinical assessments, such as HUT, the VM, and cardiopulmonary exercise stress testing. The model can also be applied as a framework for representing and simulating individual patients and pathologies. Moreover, it can serve as a framework for integrating multi-scale organ-level models, such as for the heart or the kidneys, into a whole-body model. Here, the model is used to analyze the relative importance of chronotropic, inotropic, and peripheral vascular contributions to the whole-body cardiovascular response to exercise. It is predicted that in normal physiological conditions chronotropy and inotropy make roughly equal contributions to increasing cardiac output and cardiac power output during exercise. Under upright exercise conditions, the nonlinear pressure-volume relationship of the large veins and sympathetic-mediated venous vasoconstriction are both required to maintain preload to achieve physiological exercise levels. The developed modeling framework is built using the open Modelica modeling language and is freely distributed.

Use of a Percutaneous Ventricular Assist Device/Left Atrium to Femoral Artery Bypass System for Cardiogenic Shock.

The left atrial to femoral artery bypass (LAFAB) system is a mechanical circulatory support (MCS) device used in cardiogenic shock (CS) that bypasses the left ventricle by draining blood from the left atrium (LA) and returning it to the systemic arterial circulation via the femoral artery. It can provide flows ranging from 2.5-5 L/min depending on the size of the cannula. Here, we discuss the mechanism of action of LAFAB, available clinical data, indications for its use in cardiogenic shock, steps of implantation, post-procedural care, and complications associated with the use of this device and their management. We also provide a brief video of the procedural component of device therapy, including the pre-placement preparation, percutaneous placement of the device via transseptal puncture under echocardiographic guidance and the post-operative management of device parameters.

Effects and side effects of maternal administration of indomethacin for fetal tricuspid valve dysplasia

We report on the course of two fetuses with tricuspid valve dysplasia (TVD) who were treated with indomethacin. Case 1 presented at 24 weeks' gestation with severe tricuspid regurgitation (TR), retrograde flow in the arterial duct, no antegrade flow across the pulmonary valve and free pulmonary regurgitation (PR). There was cardiomegaly and fetal hydrops with ascites, skin edema and pleural effusion. The Simpson–Andrews–Sharland (SAS) prenatal severity score for TVD was 7, which predicted fetal demise. The SAS score ranges from 0 to 10, with no predicted survivors scoring ≥ 51. Case 2 presented at 16 weeks' gestation with moderate TR, antegrade flow across the pulmonary valve, progressing to functional pulmonary atresia by 21 weeks' gestation, and a SAS score of 4. At 33 + 5 weeks, there was evidence of further progression with increasing cardiomegaly (cardiothoracic ratio (CTR): 0.80), severe TR and PR and a SAS score of 8. Estimated fetal weight (EFW) dropped from 17th to 3rd centile, umbilical artery (UA) pulsatility index was > 95th centile and amniotic fluid index (AFI) was normal (8.9 cm). Maternal indomethacin (100 mg three times a day (TDS)) was commenced in both cases (Figure 1), leading to constriction/closure of the arterial duct, reduction in PR and antegrade flow across the pulmonary valve. In Case 1, by 26 weeks' gestation, fetal hydrops had completely resolved, indomethacin was replaced by ibuprofen (200 mg TDS) due to a more favorable side-effect profile. However, the arterial duct reopened and indomethacin was reintroduced. Following this, the arterial duct constricted, but oligohydramnios developed (AFI: 4.4 cm). At 30 weeks' gestation, there was faltering growth, EFW of 1.2 kg and anhydramnios. Indomethacin was stopped and the AFI normalized (17.1 cm), but cardiomegaly persisted with severe TR. Intrauterine death occurred at 31 + 6 weeks' gestation. In Case 2, following commencement of indomethacin, CTR reduced to 0.65 but oligohydramnios worsened (AFI: 4.2 cm). Indomethacin was stopped and AFI normalized. Indomethacin was restarted at a lower dose (50 mg TDS), but despite failure to constrict the arterial duct, oligohydramnios recurred (AFI: 1.5 cm) and therapy was ceased. The baby was delivered at 36 weeks' gestation due to absent end-diastolic UA flow, weighing 1.4 kg, and was stable without intervention at 1 year of age. Prenatally detected cases of TVD are often those at the most severe end of the spectrum, presenting with cardiomegaly secondary to severe TR1. Cardiomegaly leads to compression of the developing lung tissue, pulmonary hypoplasia and increased risk of postnatal demise. The fetal environment is disadvantageous for the fetus with TVD as the right ventricle (RV) faces systemic pressures and high pulmonary vascular resistance, worsening TR and subsequent right atrial dilatation, which in itself will exacerbate TR. Severe TR causes reduced antegrade flow across the pulmonary valve and reversal of flow in the arterial duct. This ‘steal’ from the systemic arterial circulation inhibits antegrade pulmonary blood flow and causes PR, which results in further volume loading of the RV. Furthermore, RV dilatation has an adverse effect on left ventricular geometry and function, causing additional fetal hemodynamic compromise2, explaining the high perinatal mortality of 45–71%3. Whilst there have been apparently favorable reports of indomethacin for a circular shunt in TVD2, 4, this treatment led to anhydramnios/oligohydramnios in both our cases. This may be due to pre-existing renal hypoperfusion secondary to poor ventricular-ventricular interaction and ductal steal. Furthermore, through its action on prostaglandins, indomethacin can lead to renal vasoconstriction and may cause oligohydramnios5. The potential benefits of ductal constriction for circular shunts need to be balanced against the risk of renal perfusion, necessitating close cardiac and fetal medicine supervision for affected fetuses. A prospective trial is needed to evaluate the risk-benefit ratio of this new treatment for fetal TVD. We acknowledge the contribution of Dr Wayne Tworetzky from the Children's Hospital in Boston, USA, whose group published the rationale for indomethacin therapy in this group of fetuses. Dr Tworetzky advised on the indomethacin and ibuprofen treatment used in the first case. Data available on request due to privacy/ethical restrictions

A Rare Pulmonary Arterio-venous Malformation with Circular Shunting Due to Inferior Phrenic Artery Supply with Pulmonary Venous Drainage: a Case Report

A rare case of a pulmonary arterio-venous malformation not requiring treatment is reported. An incidental peripheral right lower lobe intrapulmonary pulmonary arterio-venous malformation was identified on computed tomography. On catheter angiography, no pulmonary artery supply was identified. Systemic artery catheter arteriography identified systemic arterial supply from a conjoined inferior phrenic artery with pulmonary venous drainage to the left atrium. Due to this lung abnormality being a systemic arterial circulation to pulmonary venous circulation (left to left or circular) shunt, no treatment was indicated.

Detection of Shunting Into Pulmonary Artery on Multidetector Row Computed Tomography Arteriography Before Bronchial Arterial Embolization: A Preliminary Study.

The aim of this study was to investigate the diagnostic performance of detecting systemic arterial pulmonary circulation shunts on multidetector row computed tomography arteriography (MDCTA). Thirty-five consecutive bronchial artery embolization sessions with preprocedural MDCTA were performed for 32 patients and 35 sessions. The MDCTA studies with computed tomography value of pulmonary trunk visually lower than that of ascending aorta were defined as "diagnostic MDCTA." Angiographic studies and "diagnostic MDCTA" were evaluated, respectively, for shunting into pulmonary artery. Based on the results of angiographic studies, diagnostic performance of "diagnostic MDCTA" was evaluated. The rate of diagnostic MDCTA was 63% (23 of 35). On "diagnostic MDCTA," sensitivity, specificity, and positive and negative predictive values for detecting shunts were 83% 100%, 100%, 94%, respectively. Systemic arterial pulmonary circulation shunts were detected on "diagnostic MDCTA" with high sensitivity and specificity.

Extracorporeal membrane oxygenation: indications, technique and contemporary outcomes

### Learning objectives Extracorporeal membrane oxygenation (ECMO) is an advanced form of temporary life support, to aid respiratory and/or cardiac function. It has been used since the early 1970s and...

Cuff Technique for Small-Diameter Vascular Grafts in the Systemic Arterial Circulation of the Rat.

This study determined the feasibility of the cuff technique for small-caliber vascular grafts in a rat model. A graft was implanted with the cuff technique or suture technique in a 1-cm segment of the abdominal aorta in 12 rats. The mean aortic clamp time was 29 minutes with the cuff technique and 44 minutes with the suture technique; the cuff technique was significantly shorter. Abdominal angiography at 1 week after implantation showed no significant stenosis in 9 rats, focal stenosis of the mid-portion of the graft in 1 rat with each technique, and total occlusion of the graft in 1 rat with the suture technique. We have successfully used the cuff technique for anastomosis for small-caliber vascular grafts in an animal model.

Diagnosis of arterial gas embolism in SCUBA diving: modification suggestion of autopsy techniques and experience in eight cases

The purpose of this study was to suggest modifications of autopsy techniques in order to improve post-mortem diagnosis of arterial gas embolism (AGE) based on multidisciplinary investigation of SCUBA diving fatalities. Five adult human cadavers from the voluntary donation program of the Human Anatomy Laboratory, and eight judicial autopsied bodies of SCUBA divers from the Forensic Pathology Service were assessed. Before performing any autopsies, we accessed the diving plan and the divers' profiles for each case. We then introduced a new dissection procedure that included identification, isolation, and manipulation of carotid, vertebral and thoracic arterial systems. The dissected vascular structures that allowed optimall isolation of the systemic arterial circulation were identified and ligated. In three of the eight judicial cases, we had a strongly suggestive history of arterial gas embolism following pulmonary barotrauma (PBt/AGE). In these cases, the additional arterial dissection allowed us to clearly diagnose AGE in one of them. The autopsy of the rest of the cases showed other causes of death such as asphyxia by drowning and heart attack. In all cases we were able to reject decompression sickness, and in some of them we showed the presence of artefacts secondary to decomposition and resuscitation maneuvers. These results allow us to suggest a specific autopsy technique divided into four steps, aimed at confirming or excluding some evidence of dysbaric disorders according to a re-enactment of the incident. We have demonstrated the presence of large volumes of intravascular air, which is typical of PBt/AGE.

Systemic histone release disrupts plasmalemma and contributes to necrosis in acute pancreatitis

BackgroundClinical and experimental acute pancreatitis feature histone release within the pancreas from innate immune cells and acinar cell necrosis. In this study, we aimed to detail the source of circulating histones and assess their role in the pathogenesis of acute pancreatitis. MethodsCirculating nucleosomes were measured in patient plasma, taken within 24 and 48 h of onset of acute pancreatitis and correlated with clinical outcomes. Using caerulein hyperstimulation, circulating histones were measured in portal, systemic venous and systemic arterial circulation in mice, and the effects of systemic administration of histones in this model were assessed. The sites of actions of circulating histones were assessed by administration of FITC-labelled histones. The effects of histones on isolated pancreatic acinar cells were further assessed by measuring acinar cell death and calcium permeability in vitro. ResultsCell-free histones were confirmed to be abundant in human acute pancreatitis and found to derive from pancreatitis-associated liver injury in a rodent model of the disease. Fluorescein isothianate-labelled histones administered systemically targeted the pancreas and exacerbated injury in experimental acute pancreatitis. Histones induce charge- and concentration-dependent plasmalemma leakage and necrosis in isolated pancreatic acinar cells, independent of extracellular calcium. ConclusionWe conclude that histones released systemically in acute pancreatitis concentrate within the inflamed pancreas and exacerbate injury. Circulating histones may provide meaningful biomarkers and targets for therapy in clinical acute pancreatitis.

Cardiovascular adaptation to the Fontan circulation

Although medium-term survival following Fontan operations in the modern era has improved dramatically, late cardiovascular and extracardiac morbidity are common and are associated with impaired quality of life and premature late mortality. This serves as a reminder of the extraordinary adaptations required of the cardiovascular system when the systemic arterial, systemic venous and pulmonary circulations are placed in series coupled to a single ventricular pump. This article reviews the key features and principles that govern interactions between the ventricle, systemic arterial circulation, the systemic venous and pulmonary circulatory compartments, the microcirculation, and lymphatic circulations. The overarching aim is to provide insight into the integrative pathophysiology that governs the Fontan circulation and stimulate thoughtful approaches to advance research.