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Perfusion Apr 2023This study aims to determine the oxygenator impact on alterations of peramivir (PRV) in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch)...
INTRODUCTION
This study aims to determine the oxygenator impact on alterations of peramivir (PRV) in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extra-corporeal membrane oxygenation (ECMO) circuit including the Quadrox-i oxygenator.
METHODS
1/4-inch and 3/8-inch, simulated closed-loop ECMO circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. A one-time dose of PRV was administered into the circuits and serial pre- and post-oxygenator concentrations were obtained at 5-min and 1-, 2-, 3-, 4-, 5-, 6-, 8-, 12-, and 24-h time points. PRV was also maintained in a glass vial, and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation
RESULTS
For the 1/4-in. circuit with an oxygenator, there was < 15% PRV loss, and for the 1/4-in. circuit without an oxygenator, there was < 3% PRV loss during the study period. For the 3/8-in. circuits with an oxygenator, there was < 15% PRV loss, and for the 3/8-in. circuits without an oxygenator, there was < 3% PRV loss during the study period.
CONCLUSION
There was no significant PRV loss over the 24-h study period in either the 1/4-in. or 3/8-in circuit, regardless of the presence of the oxygenator. The concentrations obtained pre- and post-oxygenator appeared to approximate each other, suggesting there may be no drug loss the oxygenator. This preliminary data suggests PRV dosing may not need to be adjusted for concern of drug loss the oxygenator. Additional single and multiple dose studies are needed to validate these findings.
Topics: Infant, Newborn; Adult; Adolescent; Child; Humans; Oxygenators, Membrane; Extracorporeal Membrane Oxygenation
PubMed: 35225084
DOI: 10.1177/02676591211060975 -
Free Radical Biology & Medicine Aug 2019Looking across our planet's four-and-a-half billion-year history, the rise of dioxygen-an interval sometimes called the Great Oxygenation Event (GOE)-is arguably the...
Looking across our planet's four-and-a-half billion-year history, the rise of dioxygen-an interval sometimes called the Great Oxygenation Event (GOE)-is arguably the most important environmental change. This revolution occurred approximately 2.3 billion years ago, roughly at the mid-way point in Earth history, and it was ultimately driven by a biological innovation: the evolution of oxygenic photosynthesis. The evolution of oxygenic photosynthesis conferred the ability to use water as a photosynthetic substrate (earlier photosynthesis was anoxygenic and required reduced iron, sulfur, carbon, or hydrogen). Primary productivity-no longer limited by a source of electrons-greatly expanded across the Earth surface. In turn, dioxygen accumulated and became widely available for use in anabolic and catabolic metabolisms, forming a rich cascade of evolutionary potential and consequence. The modern biosphere figured out how to balance harmful oxidative stress with the beneficial ways dioxygen can be used. But how did life come to first tolerate and then thrive in an oxygenated world? It's this question that attracted the diverse perspectives reflected in this special issue.
Topics: Biological Evolution; Carbon; Electrons; Humans; Hydrogen; Iron; Oxygen; Photosynthesis; Sulfur
PubMed: 31344436
DOI: 10.1016/j.freeradbiomed.2019.07.021 -
ASAIO Journal (American Society For... Oct 2022Extracorporeal membrane oxygenation (ECMO) has been advancing rapidly due to a combination of rising rates of acute and chronic lung diseases as well as significant...
Extracorporeal membrane oxygenation (ECMO) has been advancing rapidly due to a combination of rising rates of acute and chronic lung diseases as well as significant improvements in the safety and efficacy of this therapeutic modality. However, the complexity of the ECMO blood circuit, and challenges with regard to clotting and bleeding, remain as barriers to further expansion of the technology. Recent advances in microfluidic fabrication techniques, devices, and systems present an opportunity to develop new solutions stemming from the ability to precisely maintain critical dimensions such as gas transfer membrane thickness and blood channel geometries, and to control levels of fluid shear within narrow ranges throughout the cartridge. Here, we present a physiologically inspired multilayer microfluidic oxygenator device that mimics physiologic blood flow patterns not only within individual layers but throughout a stacked device. Multiple layers of this microchannel device are integrated with a three-dimensional physiologically inspired distribution manifold that ensures smooth flow throughout the entire stacked device, including the critical entry and exit regions. We then demonstrate blood flows up to 200 ml/min in a multilayer device, with oxygen transfer rates capable of saturating venous blood, the highest of any microfluidic oxygenator, and a maximum blood flow rate of 480 ml/min in an eight-layer device, higher than any yet reported in a microfluidic device. Hemocompatibility and large animal studies utilizing these prototype devices are planned. Supplemental Visual Abstract, http://links.lww.com/ASAIO/A769.
Topics: Animals; Biomimetics; Equipment Design; Microfluidics; Oxygen; Oxygenators
PubMed: 36194101
DOI: 10.1097/MAT.0000000000001647 -
Antioxidants & Redox Signaling Nov 2022Oxygen levels are key regulators of virtually every living mammalian cell, under both physiological and pathological conditions. Starting from embryonic and fetal... (Review)
Review
Oxygen levels are key regulators of virtually every living mammalian cell, under both physiological and pathological conditions. Starting from embryonic and fetal development, through the growth, onset, and progression of diseases, oxygen is a subtle, although pivotal, mediator of key processes such as differentiation, proliferation, autophagy, necrosis, and apoptosis. Hypoxia-driven modifications of cellular physiology are investigated in depth or for their clinical and translational relevance, especially in the ischemic scenario. The mild or severe lack of oxygen is, undoubtedly, related to cell death, although abundant evidence points at oscillating oxygen levels, instead of permanent low pO, as the most detrimental factor. Different cell types can consume oxygen at different rates and, most interestingly, some cells can shift from low to high consumption according to the metabolic demand. Hence, we can assume that, in the intracellular compartment, oxygen tension varies from low to high levels depending on both supply and consumption. The positive balance between supply and consumption leads to a pro-oxidative environment, with some cell types facing hypoxia/hyperoxia cycles, whereas some others are under fairly constant oxygen tension. Within this frame, the alterations of oxygen levels (dysoxia) are critical in two paradigmatic organs, the heart and brain, under physiological and pathological conditions and the interactions of oxygen with other physiologically relevant gases, such as nitric oxide, can alternatively contribute to the worsening or protection of ischemic organs. Further, the effects of dysoxia are of pivotal importance for iron metabolism. 37, 972-989.
Topics: Animals; Humans; Oxygen; Hypoxia; Hyperoxia; Oxygen Consumption; Cell Hypoxia; Mammals
PubMed: 35412859
DOI: 10.1089/ars.2021.0232 -
Cell Reports Apr 2023The mitochondrial response to changes in cellular energy demand is necessary for cellular adaptation and organ function. Many genes are essential in orchestrating this...
The mitochondrial response to changes in cellular energy demand is necessary for cellular adaptation and organ function. Many genes are essential in orchestrating this response, including the transforming growth factor (TGF)-β1 target gene Mss51, an inhibitor of skeletal muscle mitochondrial respiration. Although Mss51 is implicated in the pathophysiology of obesity and musculoskeletal disease, how Mss51 is regulated is not entirely understood. Site-1 protease (S1P) is a key activator of several transcription factors required for cellular adaptation. However, the role of S1P in muscle is unknown. Here, we identify S1P as a negative regulator of muscle mass and mitochondrial respiration. S1P disruption in mouse skeletal muscle reduces Mss51 expression and increases muscle mass and mitochondrial respiration. The effects of S1P deficiency on mitochondrial activity are counteracted by overexpressing Mss51, suggesting that one way S1P inhibits respiration is by regulating Mss51. These discoveries expand our understanding of TGF-β signaling and S1P function.
Topics: Animals; Mice; Cell Respiration; Mitochondria; Muscle, Skeletal; Signal Transduction; Transforming Growth Factor beta
PubMed: 37002920
DOI: 10.1016/j.celrep.2023.112336 -
Advanced Healthcare Materials Aug 2023Hypoxia is a typical feature of most solid tumors and has important effects on tumor cells' proliferation, invasion, and metastasis. This is the key factor that leads to... (Review)
Review
Hypoxia is a typical feature of most solid tumors and has important effects on tumor cells' proliferation, invasion, and metastasis. This is the key factor that leads to poor efficacy of different kinds of therapy including chemotherapy, radiotherapy, photodynamic therapy, etc. In recent years, the construction of hypoxia-relieving functional nanoplatforms through nanotechnology has become a new strategy to reverse the current situation of tumor microenvironment hypoxia and improve the effectiveness of tumor treatment. Here, the main strategies and recent progress in constructing nanoplatforms are focused on to directly carry oxygen, generate oxygen in situ, inhibit mitochondrial respiration, and enhance blood perfusion to alleviate tumor hypoxia. The advantages and disadvantages of these nanoplatforms are compared. Meanwhile, nanoplatforms based on organic and inorganic substances are also summarized and classified. Through the comprehensive overview, it is hoped that the summary of these nanoplatforms for alleviating hypoxia could provide new enlightenment and prospects for the construction of nanomaterials in this field.
Topics: Humans; Tumor Hypoxia; Neoplasms; Photochemotherapy; Oxygen; Hypoxia; Tumor Microenvironment; Cell Line, Tumor; Photosensitizing Agents
PubMed: 37055912
DOI: 10.1002/adhm.202300089 -
Artificial Organs Mar 2021Venoarterial extracorporeal membrane oxygenation (VA-ECMO) serves as a conventional short-term mechanical circulatory assist to support heart and lung functions. The... (Observational Study)
Observational Study
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) serves as a conventional short-term mechanical circulatory assist to support heart and lung functions. The short-term ventricular assist devices (ST-VAD) can, on the contrary, offer only circulatory support. A combination of VAD and oxygenator (Oxy-VAD) could help overcome this potential disadvantage. This is a retrospective case note study of patients supported on ST-VAD which required adding an oxygenator for extra respiratory support. The oxygenator was introduced in the ST-VAD circuit, either on the left or the right side. Twenty-two patients with the etiology of refractory cardiogenic shock in decompensation were supported on Oxy-VAD between years 2009 and 2019 at tertiary care . All patients were classified into class-I INTERMACS with a mean SOFA Score of 14 ± 2.58. 86.4% of patients were already on mechanical support pre-ST-VAD implant, 80% on VA-ECMO. The BiVAD implant accounted for 63.6%, followed by LVAD and RVAD with 27.3% and 9.1%. Mean duration of the ST-VAD was 8.5 days. The oxygenator was introduced in 14 RVAD and 8 LVAD circuits. The oxygenator was successfully weaned in 54.5% while ST-VAD was explanted in 31.8%. Discharge to home survival was 22.7%. Oxy-VAD proves a viable, and probably, a better option to VA-ECMO in acute cardiorespiratory decompensation. It offers organ-specific tailor-made support to the right and/or left heart and/or lungs. While on Oxy-VAD support, each organ performance can be assessed independently, and the assistance of the specifically improved organ can be weaned off without discontinuing the support for the rest.
Topics: Adult; Aged; Cardiopulmonary Resuscitation; Female; Heart Failure; Heart-Assist Devices; Humans; Male; Middle Aged; Organ Dysfunction Scores; Oxygenators; Prospective Studies; Respiratory Insufficiency; Retrospective Studies; Time Factors; Treatment Outcome
PubMed: 32885472
DOI: 10.1111/aor.13813 -
Artificial Organs Nov 2022Training is an essential aspect of providing high-quality treatment and ensuring patient safety in any medical practice. Because extracorporeal membrane oxygenation...
BACKGROUND
Training is an essential aspect of providing high-quality treatment and ensuring patient safety in any medical practice. Because extracorporeal membrane oxygenation (ECMO) is a complicated operation with various elements, variables, and irregular situations, doctors must be experienced and knowledgeable about all conventional protocols and emergency procedures. The conventional simulation approach has a number of limitations. The approach is intrinsically costly since it relies on disposable medical equipment (i.e., oxygenators, heat exchangers, and pumps) that must be replaced regularly due to the damage caused by the liquid used to simulate blood. The oxygenator, which oxygenates the blood through a tailored membrane in ECMO, acts as a replacement for the patient's natural lung. For the context of simulation-based training (SBT) oxygenators are often expensive and cannot be recycled owing to contamination issues.
METHODS
Consequently, it is advised that the training process include a simulated version of oxygenators to optimize reusability and decrease training expenses. Toward this goal, this article demonstrates a mock oxygenator for ECMO SBT, designed to precisely replicate the real machine structure and operation.
RESULTS
The initial model was reproduced using 3D modeling and printing. Additionally, the mock oxygenator could mimic frequent events such as pump noise and clotting. Furthermore, the oxygenator is integrated with the modular ECMO simulator using cloud-based communication technology that goes in hand with the internet of things technology to provide remote control via an instructor tablet application.
CONCLUSIONS
The final 3D modeled oxygenator body was tested and integrated with the other simulation modules at Hamad Medical Corporation with several participants to evaluate the effectiveness of the training session.
Topics: Humans; Extracorporeal Membrane Oxygenation; Oxygenators; Simulation Training; Lung; Computer Simulation; Oxygenators, Membrane
PubMed: 35578949
DOI: 10.1111/aor.14318 -
Artificial Organs Nov 2020Lung transplantation may be a final destination therapy in lung failure, but limited donor organ availability creates a need for alternative management, including... (Review)
Review
Lung transplantation may be a final destination therapy in lung failure, but limited donor organ availability creates a need for alternative management, including artificial lung technology. This invited review discusses ongoing developments and future research pathways for respiratory assist devices and tissue engineering to treat advanced and refractory lung disease. An overview is also given on the aftermath of the coronavirus disease 2019 pandemic and lessons learned as the world comes out of this situation. The first order of business in the future of lung support is solving the problems with existing mechanical devices. Interestingly, challenges identified during the early days of development persist today. These challenges include device-related infection, bleeding, thrombosis, cost, and patient quality of life. The main approaches of the future directions are to repair, restore, replace, or regenerate the lungs. Engineering improvements to hollow fiber membrane gas exchangers are enabling longer term wearable systems and can be used to bridge lung failure patients to transplantation. Progress in the development of microchannel-based devices has provided the concept of biomimetic devices that may even enable intracorporeal implantation. Tissue engineering and cell-based technologies have provided the concept of bioartificial lungs with properties similar to the native organ. Recent progress in artificial lung technologies includes continued advances in both engineering and biology. The final goal is to achieve a truly implantable and durable artificial lung that is applicable to destination therapy.
Topics: COVID-19; Extracorporeal Membrane Oxygenation; Humans; Intensive Care, Neonatal; Oxygenators; Tissue Engineering; Wearable Electronic Devices
PubMed: 33098217
DOI: 10.1111/aor.13801 -
Biomolecules Jul 2021Nanomaterial-mediated cancer therapeutics is a fast developing field and has been utilized in potential clinical applications. However, most effective therapies, such as... (Review)
Review
Nanomaterial-mediated cancer therapeutics is a fast developing field and has been utilized in potential clinical applications. However, most effective therapies, such as photodynamic therapy (PDT) and radio therapy (RT), are strongly oxygen-dependent, which hinders their practical applications. Later on, several strategies were developed to overcome tumor hypoxia, such as oxygen carrier nanomaterials and oxygen generated nanomaterials. Among these, oxygen species generation on nanozymes, especially catalase (CAT) mimetic nanozymes, convert endogenous hydrogen peroxide (HO) to oxygen (O) and peroxidase (POD) mimetic nanozymes converts endogenous HO to water (HO) and reactive oxygen species (ROS) in a hypoxic tumor microenvironment is a fascinating approach. The present review provides a detailed examination of past, present and future perspectives of POD mimetic nanozymes for effective oxygen-dependent cancer phototherapeutics.
Topics: Animals; Biomimetic Materials; Humans; Nanostructures; Neoplasms; Oxygen; Peroxidase; Photochemotherapy; Tumor Hypoxia; Tumor Microenvironment
PubMed: 34356639
DOI: 10.3390/biom11071015