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Cannulation strategies in aortic arch surgeries are a matter of immense discussion. Majority of time deep hypothermic circulatory arrest (DHCA) is the way out, but it does come with its set of demerits. Here we demonstrate a case with aortic arch dissection dealt with dual cannulation strategy in axillary and femoral artery without need for DHCA and ensuring complete neuroprotection of brain and spinal cord without hinderance of time factor. Inception of new ideas like this may decrease the need for DHCA and hence its drawbacks, thus decreasing the morbidity and mortality associated.
Subject(s)
Aortic Dissection , Heart Transplantation , Humans , Aortic Dissection/surgery , Aortic Dissection/etiology , Heart Transplantation/adverse effects , Male , Aortic Aneurysm, Thoracic/surgery , Aortic Aneurysm, Thoracic/diagnostic imaging , Circulatory Arrest, Deep Hypothermia Induced , Middle Aged , Femoral Artery/surgery , Postoperative ComplicationsABSTRACT
Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a feasible and effective rescue strategy for prolonged cardiac arrest (CA). However, prolonged total body ischemia and reperfusion can cause microvascular occlusion that prevents organ reperfusion and recovery of function. One hypothesized mechanism of microvascular "no-reflow" is leukocyte adhesion and formation of neutrophil extracellular traps. In this study we tested the hypothesis that a leukocyte filter (LF) or leukocyte modulation device (L-MOD) could reduce NETosis and improve recovery of heart and brain function in a swine model of prolonged cardiac arrest treated with ECPR. Thirty-six swine (45.5 ± 2.5 kg, evenly distributed sex) underwent 8 min of untreated ventricular fibrillation CA followed by 30 min of mechanical CPR with subsequent 8 h of ECPR. Two females were later excluded from analysis due to CPR complications. Swine were randomized to standard care (Control group), LF, or L-MOD at the onset of CPR. NET formation was quantified by serum dsDNA and citrullinated histone as well as immunofluorescence staining of the heart and brain for citrullinated histone in the microvasculature. Primary outcomes included recovery of cardiac function based on cardiac resuscitability score (CRS) and recovery of neurologic function based on the somatosensory evoked potential (SSEP) N20 cortical response. In this model of prolonged CA treated with ECPR we observed significant increases in serum biomarkers of NETosis and immunohistochemical evidence of microvascular NET formation in the heart and brain that were not reduced by LF or L-MOD therapy. Correspondingly, there were no significant differences in CRS and SSEP recovery between Control, LF, and L-MOD groups 8 h after ECPR onset (CRS = 3.1 ± 2.7, 3.7 ± 2.6, and 2.6 ± 2.6 respectively; p = 0.606; and SSEP = 27.9 ± 13.0%, 36.7 ± 10.5%, and 31.2 ± 9.8% respectively, p = 0.194). In this model of prolonged CA treated with ECPR, the use of LF or L-MOD therapy during ECPR did not reduce microvascular NETosis or improve recovery of myocardial or brain function. The causal relationship between microvascular NETosis, no-reflow, and recovery of organ function after prolonged cardiac arrest treated with ECPR requires further investigation.
Subject(s)
Cardiopulmonary Resuscitation , Disease Models, Animal , Heart Arrest , Animals , Heart Arrest/therapy , Cardiopulmonary Resuscitation/methods , Swine , Female , Male , Extracorporeal Membrane Oxygenation/methods , Leukocytes , Extracellular Traps/metabolism , Leukocyte Reduction Procedures/methodsABSTRACT
Objective: Donor hearts procured after circulatory death (DCD) may significantly increase the number of hearts available for transplantation. The purpose of this study was to analyze current DCD and brain-dead donor (DBD) heart transplantation rates and characterize organ refusal using the most up-to-date United Network for Organ Sharing (UNOS) and Organ Procurement and Transplantation Network data. Methods: We analyzed UNOS and Organ Procurement and Transplantation Network DBD and DCD candidate, transplantation, and demographic data from 2020 through 2022 and 2022 refusal code data to characterize DCD heart use and refusal. Subanalyses were performed to characterize DCD donor demographics and regional transplantation rate variance. Results: DCD hearts were declined 3.37 times more often than DBD hearts. The most frequently used code for DCD refusal was neurologic function, related to concerns of a prolonged dying process and organ preservation. In 2022, 92% (1329/1452) of all DCD refusals were attributed to neurologic function. When compared with DBD, DCD donor hearts were more frequently declined as the result of prolonged warm ischemic time (odds ratio, 5.65; 95% confidence interval, 4.07-7.86) and other concerns over organ preservation (odds ratio, 4.06; 95% confidence interval, 3.33-4.94). Transplantation rate variation was observed between demographic groups and UNOS regions. DCD transplantation rates are currently experiencing second order polynomial growth. Conclusions: DCD donor hearts are declined more frequently than DBD. DCD heart refusals result from concerns over a prolonged dying process and organ preservation. Heart transplantation rates may be substantially improved by ex situ hemodynamic assessment, adoption of normothermic regional perfusion guidelines, and quality initiatives.
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Cold static storage (CSS) for up to 6â h is the gold standard in heart preservation. Although some hearts stored over 6â h have been transplanted, longer CSS times have increased posttransplant morbimortality. Transmedics® Organ Care System (OCS™) is the only FDA-approved commercial system that provides an alternative to CSS using normothermic ex situ heart perfusion (NEHP) in resting mode with aortic perfusion (Langendorff method). However, it is also limited to 6â h and lacks an objective assessment of cardiac function. Developing a system that can perfuse hearts under NEHP conditions for >24â h can facilitate organ rehabilitation, expansion of the donor pool, and objective functional evaluation. The Extracorporeal Life Support Laboratory at the University of Michigan has worked to prolong NEHP to >24â h with an objective assessment of heart viability during NEHP. An NEHP system was developed for aortic (Langendorff) perfusion using a blood-derived perfusate (leukocyte/thrombocyte-depleted blood). Porcine hearts (n = 42) of different sizes (6-55â kg) were divided into five groups and studied during 24â h NEHP with various interventions in three piglets (small-size) heart groups: (1) Control NEHP without interventions (n = 15); (2) NEHP + plasma exchange (n = 5); (3) NEHP + hemofiltration (n = 10) and two adult-size (juvenile pigs) heart groups (to demonstrate the support of larger hearts); (4) NEHP + hemofiltration (n = 5); and (5) NEHP with intermittent left atrial (iLA) perfusion (n = 7). All hearts with NEHP + interventions (n = 27) were successfully perfused for 24â h, whereas 14 (93.3%) control hearts failed between 10 and 21â h, and 1 control heart (6.6%) lasted 24â h. Hearts in the piglet hemofiltration and plasma exchange groups performed better than those in the control group. The larger hearts in the iLA perfusion group (n = 7) allowed for real-time heart functional assessment and remained stable throughout the 24â h of NEHP. These results demonstrate that heart preservation for 24â h is feasible with our NEHP perfusion technique. Increasing the preservation period beyond 24â h, infection control, and nutritional support all need optimization. This proves the concept that NEHP has the potential to increase the organ pool by (1) considering previously discarded hearts; (2) performing an objective assessment of heart function; (3) increasing the donor/recipient distance; and (4) developing heart-specific perfusion therapies.
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Rockburst phenomena pose significant challenges in the mining industry, particularly with increased underground activities at greater depths. These sudden failures not only jeopardize personnel safety but also impact mining investments. Consequently, it becomes crucial to assess the reliability and effectiveness of empirical methods employed for predicting rock burst occurrences and their severity, an ongoing subject of debate within the scientific community. This research presents a comprehensive review of empirical approaches for rock burst prediction. Subsequently, these approaches are applied to predict rock burst occurrences and its intensity within sections of a tunnel at the new level of El Teniente mine in Chile. Most of these methods rely on single-factor criteria to predict the likelihood and severity of rock bursts. However, inconsistencies are observed in the results obtained from these approaches in numerous cases. This discrepancy highlights the influence of various input parameters on rock burst estimations and emphasizes that single-index criteria may not encompass all the pertinent factors that contribute to this phenomenon. Consequently, such criteria may inadequately estimate or reflect the probability of rock burst occurrences. Given the multifaceted nature of rock burst phenomena, which depend on multiple factors, it becomes imperative to explore new approaches that consider a broader range of influencing factors, thereby yielding more realistic results. Hence, continued research is essential to develop new methods that address this issue comprehensively and ensure the safety of the mining industry.
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INTRODUCTION: A radical paradigm shift in the treatment of premature infants failing conventional treatment is to recreate fetal physiology using an extracorporeal Artificial Placenta (AP). The aim of this study is to evaluate the effects of changing fetal hemoglobin percent (HbF%) on physiology and circuit function during AP support in an ovine model. METHODS: Extremely premature lambs (n = 5) were delivered by cesarean section at 117-121 d estimated gestational age (EGA) (term = 145d), weighing 2.5 ± 0.35 kg. Lambs were cannulated using 10-14Fr cannulae for drainage via the right jugular vein and reinfusion via the umbilical vein. Lambs were intubated and lungs were filled with perfluorodecalin to a meniscus with a pressure of 5-8 cm H2O. The first option for transfusion was fetal whole blood from twins followed by maternal red blood cells. Arterial blood gases were used to titrate AP support to maintain fetal blood gas values. RESULTS: The mean survival time on circuit was 119.6 ± 39.5 h. Hemodynamic parameters and lactate were stable throughout. As more adult blood transfusions were given to maintain hemoglobin at 10 mg/dL, the HbF% declined, reaching 40% by post operative day 7. The HbF% was inversely proportional to flow rates as higher flows were required to maintain adequate oxygen saturation and perfusion. CONCLUSIONS: Transfusion of adult blood led to decreased fetal hemoglobin concentration during AP support. The HbF% was inversely proportional to flow rates. Future directions include strategies to decrease the priming volume and establishing a fetal blood bank to have blood rich in HbF.
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BACKGROUND: Cold static storage and normothermic ex vivo heart perfusion are routinely limited to 6 h. This report describes intermittent left atrial (LA) perfusion that allows cardiac functional assessment in a working heart mode. METHODS: Using our adult porcine model, general anesthesia was induced and a complete cardiectomy was performed following cardioplegic arrest. Back-table instrumentation was completed and normothermic ex vivo heart perfusion (NEHP) was initiated in a nonworking heart mode (Langendorff). After 1 h of resuscitation and recovery, LA perfusion was initiated and the heart was transitioned to a coronary flow-only working heart mode for 30 min. Baseline working heart parameters were documented and the heart was returned to nonworking mode. Working heart assessments were performed for 30 min every 6 h for 24 h. RESULTS: Twenty-four-hour NEHP on 9 consecutive hearts (280â ±â 42.1 g) was successful and no significant differences were found between working heart parameters at baseline and after 24 h of perfusion. There was no difference between initial and final measurements of LA mean pressures (5.0â ±â 3.1 versus 9.0â ±â 6.5 mm Hg, P â =â 0.22), left ventricular systolic pressures (44.3â ±â 7.2 versus 39.1â ±â 9.0 mm Hg, P â =â 0.13), mean aortic pressures (30.9â ±â 5.8 versus 28.1â ±â 8.1 mm Hg, P â =â 0.37), and coronary resistance (0.174â ±â 0.046 versus 0.173â ±â 0.066 mL/min/g, P â =â 0.90). There were also no significant differences between lactate (2.4â ±â 0.5 versus 2.6â ±â 0.4 mmol/L, P â =â 0.17) and glucose (173â ±â 75 versus 156â ±â 70 mg/dL, P â =â 0.37). CONCLUSIONS: A novel model using intermittent LA perfusion to create a coronary flow-only working heart mode for assessment of ex vivo cardiac function has been successfully developed.
Subject(s)
Models, Animal , Perfusion , Animals , Perfusion/methods , Time Factors , Isolated Heart Preparation , Swine , Coronary Circulation , Organ Preservation/methods , Ventricular Function, Left , Heart Transplantation , Sus scrofaABSTRACT
American ginseng (Panax quinquefolius) is widely used due to its medicinal properties. Ontario is a major producer of cultivated American ginseng, where seeds were originally collected from the wild without any subsequent scientific selection, and thus the crop is potentially very diverse. A collection of 162 American ginseng plants was harvested from a small area in a commercial garden and phenotyped for morphological traits, such as root grade, stem length, and fresh and dry weights of roots, leaves, stems, and seeds. All of the traits showed a range of values, and correlations were observed between root and stem weights, root dry weight and leaf dry weight, as well as root and leaf fresh weights. The plants were also genotyped using single nucleotide polymorphisms (SNPs) at the PW16 locus. SNP analysis revealed 22 groups based on sequence relatedness with some groups showing no SNPs and others being more diverse. The SNP groups correlated with significant differences in some traits, such as stem length and leaf weight. This study provides insights into the genetic and phenotypic diversity of cultivated American ginseng grown under similar environmental conditions, and the relationship between different phenotypes, as well as genotype and phenotype, will aid in future selection programs to develop American ginseng cultivars with desirable agronomic traits.
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BACKGROUND: Children with end-stage lung disease are commonly managed with extracorporeal life support (ECLS) as a bridge to lung transplantation. A pumpless artificial lung (MLung) is a portable alternative to ECLS and it allows for ambulation. Both ECLS and pumpless artificial lungs require systemic anticoagulation which is associated with hemorrhagic complications. We tested the MLung with a novel Nitric Oxide (NO) Surface Anticoagulation (NOSA) system, to provide local anticoagulation for 72 h of support in a pediatric-size ovine model. METHODS: Four mini sheep underwent thoracotomy and cannulation of the pulmonary artery (inflow) and left atrium (outflow), recovered and were monitored for 72hr. The circuit tubing and connectors were coated with the combination of an NO donor (diazeniumdiolated dibutylhexanediamine; DBHD-N2O2) and argatroban. The animals were connected to the MLung and 100 ppm of NO was added to the sweep gas. Systemic hemodynamics, blood chemistry, blood gases, and methemoglobin were collected. RESULTS: Mean device flow was 836 ± 121 mL/min. Device outlet saturation was 97 ± 4%. Pressure drop across the lung was 3.5 ± 1.5 mmHg and resistance was 4.3 ± 1.7 mmHg/L/min. Activated clotting time averaged 170 ± 45s. Methemoglobin was 2.9 ± 0.8%. Platelets declined from 590 ± 101 at baseline to 160 ± 90 at 72 h. NO flux (x10-10 mol/min/cm2) of the NOSA circuit averaged 2.8 ± 0.6 (before study) and 1.9 ± 0.1 (72 h) and across the MLung 18 ± 3 NO flux was delivered. CONCLUSION: The MLung is a more portable form of ECLS that demonstrates effective gas exchange for 72 h without hemodynamic changes. Additionally, the NOSA system successfully maintained local anticoagulation without evidence of systemic effects.
Subject(s)
Extracorporeal Membrane Oxygenation , Nitric Oxide , Animals , Humans , Sheep , Child , Methemoglobin , Lung , Hemodynamics , Anticoagulants/pharmacology , Anticoagulants/therapeutic useABSTRACT
BACKGROUND: Clinical translation of the extracorporeal artificial placenta (AP) is impeded by the high risk for intracranial hemorrhage in extremely premature newborns. The Nitric Oxide Surface Anticoagulation (NOSA) system is a novel non-thrombogenic extracorporeal circuit. This study aims to test the NOSA system in the AP without systemic anticoagulation. METHODS: Ten extremely premature lambs were delivered and connected to the AP. For the NOSA group, the circuit was coated with DBHD-N2O2/argatroban, 100 ppm nitric oxide was blended into the sweep gas, and no systemic anticoagulation was given. For the Heparin control group, a non-coated circuit was used and systemic anticoagulation was administered. RESULTS: Animals survived 6.8 ± 0.6 days with normal hemodynamics and gas exchange. Neither group had any hemorrhagic or thrombotic complications. ACT (194 ± 53 vs. 261 ± 86 s; p < 0.001) and aPTT (39 ± 7 vs. 69 ± 23 s; p < 0.001) were significantly lower in the NOSA group than the Heparin group. Platelet and leukocyte activation did not differ significantly from baseline in the NOSA group. Methemoglobin was 3.2 ± 1.1% in the NOSA group compared to 1.6 ± 0.6% in the Heparin group (p < 0.001). CONCLUSIONS: The AP with the NOSA system successfully supported extremely premature lambs for 7 days without significant bleeding or thrombosis. IMPACT: The Nitric Oxide Surface Anticoagulation (NOSA) system provides effective circuit-based anticoagulation in a fetal sheep model of the extracorporeal artificial placenta (AP) for 7 days. The NOSA system is the first non-thrombogenic circuit to consistently obviate the need for systemic anticoagulation in an extracorporeal circuit for up to 7 days. The NOSA system may allow the AP to be implemented clinically without systemic anticoagulation, thus greatly reducing the intracranial hemorrhage risk for extremely low gestational age newborns. The NOSA system could potentially be applied to any form of extracorporeal life support to reduce or avoid systemic anticoagulation.
Subject(s)
Extracorporeal Membrane Oxygenation , Premature Birth , Thrombosis , Pregnancy , Humans , Female , Sheep , Animals , Nitric Oxide , Placenta/physiology , Heparin , Hemorrhage/complications , Thrombosis/prevention & control , Anticoagulants/pharmacology , Intracranial Hemorrhages/complicationsABSTRACT
Background: The present article describes three cases of patients in cardiogenic shock (CS) with previous cardiac surgery that made them initially inoperable. Perioperative support with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) improved haemodynamic status and results in these high-risk patients. Case summary: Case 1 is a 57-year-old male morbidly obese with previous aortic valve replacement (AVR) who presented with chest pain and developed cardiac arrest. Cardiopulmonary resuscitation and femoral VA-ECMO were initiated. Three days later, a redo AVR was performed. Veno-arterial extracorporeal membrane oxygenation was maintained for 12 days, followed by 7 days of veno-venous ECMO for complete recovery. Case 2 features a 39-year-old male with two previous mitral valve replacements (MVRs). The first is due to papillary muscle rupture, and the second is due to endocarditis of the mitral prosthesis. He presented with CS and pulmonary oedema. Emergency surgery was performed and the patient was then placed in VA-ECMO. Weaning off was achieved 3 days after surgery. Case 3 is a 21-year-old female with a previous MVR due to rheumatic disease. She presented with CS, severe mitral prosthesis stenosis, and a pulmonary embolism. Femoral VA-ECMO was initiated, and one day later, she underwent a redo MVR operation. Extracorporeal membrane oxygenation was discontinued 4 days later. Discussion: Dysfunctional prosthetic valves leading to CS may benefit from a redo cardiac operation supported by a perioperative VA-ECMO to optimize haemodynamic status. Despite the results from risk prediction scores, this approach has the potential to reduce operative mortality in initial inoperable patients and allow a definitive redo cardiac surgery.
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BACKGROUND: Intraoperative pulmonary embolism (PE) with cardiac arrest (CA) represents a critical and potentially fatal condition. Available treatments include systemic thrombolysis, catheter-based thrombus fragmentation or aspiration, and surgical embolectomy. However, limited studies are focused on the optimal treatment choice for this critical condition. We present a case series and an updated review of the management of intraoperative CA secondary to PE. METHODS: A retrospective review of patients who developed high-risk intraoperative PE was performed between June 2012 and June 2022. For the updated review, a literature search on PubMed and Scopus was conducted which resulted in the inclusion of a total of 46 articles. RESULTS: A total of 196 174 major non-cardiac surgeries were performed between 2012 and 2022. Eight cases of intraoperative CA secondary to high-risk PE were identified. We found a mortality rate of 75%. Anticoagulation therapy was administered to one patient (12.5%), while two patients (25%) underwent thrombolysis, and one case (12.5%) underwent mechanical thrombectomy combined with thrombus aspiration. Based on the literature review and our 10-year experience, we propose an algorithm for the management of intraoperative CA caused by PE. CONCLUSION: The essential components for adequate management of intraoperative PE with CA include hemodynamic support, cardiopulmonary resuscitation, and the implementation of a primary perfusion intervention. The prompt identification of the criteria for each specific treatment modality, guided by the individual patient's characteristics, is necessary for an optimal approach.
Subject(s)
Heart Arrest , Pulmonary Embolism , Thrombosis , Humans , Thrombolytic Therapy/adverse effects , Thrombolytic Therapy/methods , Treatment Outcome , Pulmonary Embolism/complications , Pulmonary Embolism/surgery , Thrombosis/complications , Thrombosis/surgery , Heart Arrest/therapy , Heart Arrest/complicationsABSTRACT
Whole-eye optical coherence tomography (OCT) imaging is a promising tool in ocular biometry for cataract surgery planning, glaucoma diagnostics and myopia progression studies. However, conventional OCT systems are set up to perform either anterior or posterior eye segment scans and cannot easily switch between the two scan configurations without adding or exchanging optical components to account for the refraction of the eye's optics. Even in state-of-the-art whole-eye OCT systems, the scan configurations are pre-selected and cannot be dynamically reconfigured. In this work, we present the design, optimization and experimental validation of a reconfigurable and low-cost optical beam scanner based on three electro-tunable lenses, capable of non-mechanically controlling the beam position, angle and focus. We derive the analytical theory behind its control. We demonstrate its use in performing alternate anterior and posterior segment imaging by seamlessly switching between a telecentric focused beam scan to an angular collimated beam scan. We characterize the corresponding beam profiles and record whole-eye OCT images in a model eye and in an ex vivo rabbit eye, observing features comparable to those obtained with conventional anterior and posterior OCT scanners. The proposed beam scanner reduces the complexity and cost of other whole-eye scanners and is well suited for 2-D ocular biometry. Additionally, with the added versatility of seamless scan reconfiguration, its use can be easily expanded to other ophthalmic applications and beyond.
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BACKGROUND: Historically, cardiac transplantation relied on cold static storage at 5 °C for ex vivo myocardial preservation. Currently, machine perfusion is the standard of care at many transplant centers. These storage methods are limited to 12 hours. We sought to evaluate the efficacy of hemofiltration and filtrate replacement in adult porcine hearts using normothermic heart perfusion (NEVHP) for 24 hours. METHODS: We performed 24-hour NEVHP on 5 consecutive hearts. After anesthetic induction, sternotomy, cardioplegia administration, explantation, and back-table instrumentation, NEVHP was initiated in beating, unloaded mode. After 1 hour, plasma exchange was performed, and hemofiltration was initiated. Heart function parameters and arterial blood gasses were obtained hourly. RESULTS: All hearts (n = 5) were viable at the 24-hour mark. The average left ventricular systolic pressure at the beginning of the prep was 36.6 ± 7.9 mm Hg compared with 27 ± 5.5 mm Hg at the end. Coronary resistance at the beginning of prep was 0.79 ± 0.10 mm Hg/L/min and 0.93 ± 0.28 mm Hg/L/min at the end. Glucose levels averaged 223 ± 13.9 mg/dL, and the lactate average at the termination of prep was 2.6 ± 0.3 mmol/L. CONCLUSIONS: We successfully perfused adult porcine hearts at normothermic temperatures for 24 hours with results comparable to our pediatric porcine heart model. The next step in our research is NEVHP evaluation in a working mode using left atrial perfusion.
Subject(s)
Heart Transplantation , Hemofiltration , Humans , Adult , Child , Swine , Animals , Heart , Heart Transplantation/methods , Perfusion/methods , Lactic Acid , Organ Preservation/methodsABSTRACT
Prolonged cardiac arrest (CA) causes microvascular thrombosis which is a potential barrier to organ reperfusion during extracorporeal cardiopulmonary resuscitation (ECPR). The aim of this study was to test the hypothesis that early intra-arrest anticoagulation during cardiopulmonary resuscitation (CPR) and thrombolytic therapy during ECPR improve recovery of brain and heart function in a porcine model of prolonged out-of-hospital CA. DESIGN: Randomized interventional trial. SETTING: University laboratory. SUBJECTS: Swine. INTERVENTIONS: In a blinded study, 48 swine were subjected to 8 minutes of ventricular fibrillation CA followed by 30 minutes of goal-directed CPR and 8 hours of ECPR. Animals were randomized into four groups (n = 12) and given either placebo (P) or argatroban (ARG; 350 mg/kg) at minute 12 of CA and either placebo (P) or streptokinase (STK, 1.5 MU) at the onset of ECPR. MEASUREMENTS AND MAIN RESULTS: Primary outcomes included recovery of cardiac function measured by cardiac resuscitability score (CRS: range 0-6) and recovery of brain function measured by the recovery of somatosensory-evoked potential (SSEP) cortical response amplitude. There were no significant differences in recovery of cardiac function as measured by CRS between groups (p = 0.16): P + P 2.3 (1.0); ARG + P = 3.4 (2.1); P + STK = 1.6 (2.0); ARG + STK = 2.9 (2.1). There were no significant differences in the maximum recovery of SSEP cortical response relative to baseline between groups (p = 0.73): P + P = 23% (13%); ARG + P = 20% (13%); P + STK = 25% (14%); ARG + STK = 26% (13%). Histologic analysis demonstrated reduced myocardial necrosis and neurodegeneration in the ARG + STK group relative to the P + P group. CONCLUSIONS: In this swine model of prolonged CA treated with ECPR, early intra-arrest anticoagulation during goal-directed CPR and thrombolytic therapy during ECPR did not improve initial recovery of heart and brain function but did reduce histologic evidence of ischemic injury. The impact of this therapeutic strategy on the long-term recovery of cardiovascular and neurological function requires further investigation.
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Portable artificial lung (AL) systems are under development, but there are few technologies available that adjust the carbon dioxide (CO 2 ) removal in response to changes in patient metabolic needs. Our work describes the second generation of a CO 2 -based portable servoregulation system that automatically adjusts CO 2 removal in ALs. Four adult sheep (68 ± 14.3 kg) were used to test the servoregulator. The servoregulator controlled air sweep flow through the lung to meet a target exhaust gas CO 2 (tEGCO 2 ) level in normocapnic and hypercapnic (arterial partial pressure of CO 2 [PaCO 2 ] >60 mm Hg) conditions at varying flow rates (0.5-1.5 L/min) and at tEGCO 2 levels of 10, 20, and 40 mm Hg. In hypercapnic sheep, average post-AL blood partial pressure of CO 2 (pCO 2 ) values were 22.4 ± 3.6 mm Hg for tEGCO 2 of 10 mm Hg, 28.0 ± 4.1 mm Hg for tEGCO 2 of 20 mm Hg and 40.6 ± 4.8 mm Hg for tEGCO 2 of 40 mm Hg. The controller successfully and automatically adjusted the sweep gas flow to rapidly (<10 minutes) meet the tEGCO 2 level when challenged with changes in inlet blood flow or target EGCO 2 levels for all animals. These in vivo data demonstrate an important step toward portable ALs that can automatically modulate CO 2 removal and allow for substantial changes in patient activity or disease status in ambulatory applications.
Subject(s)
Extracorporeal Membrane Oxygenation , Hemodynamics , Animals , Sheep , Carbon Dioxide , Hypercapnia , Lung/metabolismABSTRACT
Defective few-layered graphene mesostructures (DFLGMs) are produced from graphite flakes by high-energy milling processes. We obtain an accurate control of the generated mesostructures, as well as of the amount and classification of the structural defects formed, providing a functional material for microwave absorption purposes. Working under far-field conditions, competitive values of minimum reflection loss coefficient (RLmin) = -21.76 dB and EAB = 4.77 dB are achieved when DFLGMs are immersed in paints at a low volume fraction (1.95%). One step forward is developed by combining them with the excellent absorption behavior that offers amorphous Fe73.5Si13.5B9Cu1Nb microwires (MWs), varying their filling contents, which are below 3%. We obtain a RLmin improvement of 47% (-53.08 dB) and an EAB enhancement of 137% (4 dB) compared to those obtained by MW-based paints. Furthermore, a fmin tunability is demonstrated, maintaining similar RLmin and EAB values, irrespective of an ideal matching thickness. In this scenario, the Maxwell-Garnet standard model is valid, and dielectric losses mainly come from multiple reflections, interfacial and dielectric polarizations, which greatly boost the microwave attenuation of MWs. The present concept can remarkably enhance not only the MW attenuation but can also apply to other microwave absorption architectures of technological interest by adding low quantities of DFLGMs.
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PURPOSE: Breast cancer risk is elevated in pathogenic germline BRCA 1/2 mutation carriers due to compromised DNA quality control. We hypothesized that if immunosurveillance promotes tumor suppression, then normal/benign breast lobules from BRCA carriers may demonstrate higher immune cell densities. METHODS: We assessed immune cell composition in normal/benign breast lobules from age-matched women with progressively increased breast cancer risk, including (1) low risk: 19 women who donated normal breast tissue to the Komen Tissue Bank (KTB) at Indiana University Simon Cancer Center, (2) intermediate risk: 15 women with biopsy-identified benign breast disease (BBD), and (3) high risk: 19 prophylactic mastectomies from women with germline mutations in BRCA1/2 genes. We performed immunohistochemical stains and analysis to quantitate immune cell densities from digital images in up to 10 representative lobules per sample. Median cell counts per mm2 were compared between groups using Wilcoxon rank-sum tests. RESULTS: Normal/benign breast lobules from BRCA carriers had significantly higher densities of immune cells/mm2 compared to KTB normal donors (all p < 0.001): CD8 + 354.4 vs 150.9; CD4 + 116.3 vs 17.7; CD68 + 237.5 vs 57.8; and CD11c + (3.5% vs 0.4% pixels positive). BBD tissues differed from BRCA carriers only in CD8 + cells but had higher densities of CD4 + , CD11c + , and CD68 + immune cells compared to KTB donors. CONCLUSIONS: These preliminary analyses show that normal/benign breast lobules of BRCA mutation carriers contain increased immune cells compared with normal donor breast tissues, and BBD tissues appear overall more similar to BRCA carriers.