Oxygen Perfusion Research Articles

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Commentary: More is better: Hybrid and parallel extracorporeal membrane oxygenation circuits

The application of extracorporeal membrane oxygenation (ECMO) for treatment of respiratory and/or cardiac failure has increased over the past decade.1 Expansion of indications and inclusion of higher-risk patients has increased the number of challenging clinical scenarios in which limitations in oxygen delivery with conventional ECMO circuits are encountered during support. In this issue of the JTCVS Techniques, Shah and colleagues2 from the University of Maryland review the use of hybrid and parallel ECMO circuits in clinical scenarios in which standard venoarterial (VA) or venovenous (VV) ECMO circuits fail to provide adequate oxygen delivery or perfusion and provide a number of important management and technical observations and recommendations.

Palliative Wound Care for PALTC

Palliative Wound Care for PALTC

Roles and mechanisms of stem cell in wound healing.

Wound healing phases comprise of highly synchronized process that begins due to a damage and restores the integrity of the injured tissues. Wound healing reduces the damage in tissue and supply sufficient oxygen and tissue perfusion, provide proper nourishment and humid wound healing atmosphere to re-establish the essential status of exaggerated parts. The untreated wound becomes susceptible for pus development, bacterial infection and complications like sepsis. Traditional and modern approaches are in practice to treat acute, open and chronic injuries, however, present wound care management has met with challenges and minimal positive effects. Stem cells have possible wound healing capability to overwhelm restrictions of the current wound care practices as it produces faster tissue regeneration in wound repair. Stem cells are unspecialized cells derived from adult body tissues and embryos that differentiate into any cell of an organism and capable of self-regeneration. The understanding on molecular mechanisms of stem cells has become the central and promising field in scientific study. This review focuses on the pre-existing traditional and modern treatments for wound healing, and types and roles of stem cells in wound care management. This review also focuses on the fundamental molecular characterization and factors influencing the molecular mechanisms of stem cells in wound healing.

Blood oxygen level dependent fMRI and perfusion MRI in the sheep brain

The ovine model could be an effective translational model but remains underexplored. Here, Blood Oxygen Level dependent functional MRI during visual stimulation and resting-state perfusion MRI were explored. We aimed at investigating the impact of isoflurane anesthesia during visual stimulation and evaluate resting cerebral blood flow and cerebral blood volume parameters in the lamb and adult sheep brain.BOLD fMRI and perfusion MRI after a bolus of DOTAREM were conducted in 4 lambs and 6 adult ewes at 3 T. A visual stimulation paradigm was delivered during fMRI at increasing isoflurane doses (1–3%).Robust but weak BOLD responses (0.21 ± 0.08%) were found in the lateral geniculate nucleus (LGN) up to 3% isoflurane anaesthesia. No significant differences were found beween BOLD responses in the range 1 to 3% ISO (p > 0.05). However, LGN cluster size decreased and functional localization became less reliable at high ISO doses (2.5–3% ISO). BOLD responses were weaker in adult sheep than in lambs (4.6 ± 1.5 versus 13.6 ± 8.5; p = 0.08). Relative cerebral blood volumes (rCBV) and relative cerebral blood flows (rCBF) were significantly higher (p < 0.0001) in lambs than in adult sheep for both gray and white matter.The impact of volatile anesthesia was explored for the first time on BOLD responses demonstrating increased reliability of functional localization of brain activity at low doses. Perfusion MRI was conducted for the first time in both lambs and adult ewes. Assessment of baseline cerebrovascular values are of interest for future studies of brain diseases allowing an improved interpretation of BOLD responses.

Sequentially Targeting Cancer‐Associated Fibroblast and Mitochondria Alleviates Tumor Hypoxia and Inhibits Cancer Metastasis by Preventing “Soil” Formation and “Seed” Dissemination

AbstractTumor metastasis is facilitated by the formation of the premetastatic niche (PMN) in destination organs and the dissemination of cancer cells detached from a primary tumor. This study reports a sequential combination strategy that exerts a profound anti‐metastasis effect by inhibiting both PMN formation and cancer cell dissemination. The approach consists of (1) cancer‐associated fibroblast cells (CAFs)‐targeting liposome and (2) mitochondria‐targeting polymer. The liposome depletes CAFs and reduces tumor stroma, leading to a significant increase in intratumoral oxygen perfusion. The polymer disrupts mitochondria aerobic respiration in cancer cells, leading to a considerable decrease in intratumoral oxygen consumption. With the complementary mechanisms, their combination drastically alleviates the hypoxia in orthotopic breast tumor and inhibits the pulmonary PMN formation by downregulating various hypoxia‐induced PMN‐fostering factors. In addition, the CAFs depletion by the liposome abrogates the metastasis‐promoting crosstalk with cancer cells; meanwhile, mitochondria dysfunction by the polymer cuts off the energy supply that supports metastasis, together resulting in an efficient suppression of cancer cell dissemination. With the two‐pronged strategy targeting these two aspects, the primary tumor is prominently inhibited, and distant metastasis is completely eradicated. This study provides a generalizable approach of sequential CAFs depletion and mitochondria disruption to combat metastatic tumors.

A Stress Syndrome Prototype Reflects Type 3 Diabetes and Ischemic Stroke Risk: The SABPA Study.

Simple SummaryThe relationship between diabetes, dementia and neuronal injury defines type 3 diabetes (T3D). Similar retinal vessel changes were observed in Alzheimer’s and chronic stressed individuals. The aim was to assess associations of chronic stress with T3D and retina pathology. An established validated chronic stress and stroke risk score (hereafter Stress) stratified participants into Stressed (high stress) and non-Stressed (low stress) groups. Early dementia signs (insulin sensitivity, cognitive dysfunction, neuronal injury) were evident in Stressed compared to non-Stressed individuals. Stress was associated with poor retinal oxygen perfusion, potentiating glaucoma risk. Stress was further related to four dementia risk markers (cognitive dysfunction; telomere shortening, neuronal injury and waist circumference), which comprised a novel Stress syndrome prototype. This prototype showed high risk for T3D as well as retinal vein widening and perfusion deficits, indicating stroke risk. Findings should increase awareness on the detrimental role of chronic stress in the human brain.Type 3 diabetes (T3D) accurately reflects that dementia, e.g., Alzheimer’s disease, represents insulin resistance and neurodegeneration in the brain. Similar retinal microvascular changes were observed in Alzheimer’s and chronic stressed individuals. Hence, we aimed to show that chronic stress relates to T3D dementia signs and retinopathy, ultimately comprising a Stress syndrome prototype reflecting risk for T3D and stroke. A chronic stress and stroke risk phenotype (Stressed) score, independent of age, race or gender, was applied to stratify participants (N = 264; aged 44 ± 9 years) into high stress risk (Stressed, N = 159) and low stress risk (non-Stressed, N = 105) groups. We determined insulin resistance using the homeostatic model assessment (HOMA-IR), which is interchangeable with T3D, and dementia risk markers (cognitive executive functioning (cognitiveexe-func); telomere length; waist circumference (WC), neuronal glia injury; neuron-specific enolase/NSE, S100B). Retinopathy was determined in the mydriatic eye. The Stressed group had greater incidence of HOMA-IR in the upper quartile (≥5), larger WC, poorer cognitiveexe-func control, shorter telomeres, consistently raised neuronal glia injury, fewer retinal arteries, narrower arteries, wider veins and a larger optic cup/disc ratio (C/D) compared to the non-Stressed group. Furthermore, of the stroke risk markers, arterial narrowing was related to glaucoma risk with a greater C/D, whilst retinal vein widening was related to HOMA-IR, poor cognitiveexe-func control and neuronal glia injury (Adjusted R2 0.30; p ≤ 0.05). These associations were not evident in the non-Stressed group. Logistic regression associations between the Stressed phenotype and four dementia risk markers (cognitiveexe-func, telomere length, NSE and WC) comprised a Stress syndrome prototype (area under the curve 0.80; sensitivity/specificity 85%/58%; p ≤ 0.001). The Stress syndrome prototype reflected risk for HOMA-IR (odds ratio (OR) 7.72) and retinal glia ischemia (OR 1.27) and vein widening (OR 1.03). The Stressed phenotype was associated with neuronal glia injury and retinal ischemia, potentiating glaucoma risk. The detrimental effect of chronic stress exemplified a Stress syndrome prototype reflecting risk for type 3 diabetes, neurodegeneration and ischemic stroke.

Voxelized simulation of cerebral oxygen perfusion elucidates hypoxia in aged mouse cortex.

Departures of normal blood flow and metabolite distribution from the cerebral microvasculature into neuronal tissue have been implicated with age-related neurodegeneration. Mathematical models informed by spatially and temporally distributed neuroimage data are becoming instrumental for reconstructing a coherent picture of normal and pathological oxygen delivery throughout the brain. Unfortunately, current mathematical models of cerebral blood flow and oxygen exchange become excessively large in size. They further suffer from boundary effects due to incomplete or physiologically inaccurate computational domains, numerical instabilities due to enormous length scale differences, and convergence problems associated with condition number deterioration at fine mesh resolutions. Our proposed simple finite volume discretization scheme for blood and oxygen microperfusion simulations does not require expensive mesh generation leading to the critical benefit that it drastically reduces matrix size and bandwidth of the coupled oxygen transfer problem. The compact problem formulation yields rapid and stable convergence. Moreover, boundary effects can effectively be suppressed by generating very large replica of the cortical microcirculation in silico using an image-based cerebrovascular network synthesis algorithm, so that boundaries of the perfusion simulations are far removed from the regions of interest. Massive simulations over sizeable portions of the cortex with feature resolution down to the micron scale become tractable with even modest computer resources. The feasibility and accuracy of the novel method is demonstrated and validated with in vivo oxygen perfusion data in cohorts of young and aged mice. Our oxygen exchange simulations quantify steep gradients near penetrating blood vessels and point towards pathological changes that might cause neurodegeneration in aged brains. This research aims to explain mechanistic interactions between anatomical structures and how they might change in diseases or with age. Rigorous quantification of age-related changes is of significant interest because it might aide in the search for imaging biomarkers for dementia and Alzheimer’s disease.

Engineering new microvascular networks on-chip: ingredients, assembly, and best practices.

Tissue engineered grafts show great potential as regenerative implants for diseased or injured tissues within the human body. However, these grafts suffer from poor nutrient perfusion and waste transport, thus decreasing their viability post-transplantation. Graft vascularization is therefore a major area of focus within tissue engineering because biologically relevant conduits for nutrient and oxygen perfusion can improve viability post-implantation. Many researchers utilize microphysiological systems as testing platforms for potential grafts due to an ability to integrate vascular networks as well as biological characteristics such as fluid perfusion, 3D architecture, compartmentalization of tissue-specific materials, and biophysical and biochemical cues. While many methods of vascularizing these systems exist, microvascular self-assembly has great potential for bench-to-clinic translation as it relies on naturally occurring physiological events. In this review, we highlight the past decade of literature and critically discuss the most important and tunable components yielding a self-assembled vascular network on chip: endothelial cell source, tissue-specific supporting cells, biomaterial scaffolds, biochemical cues, and biophysical forces. This article discusses the bioengineered systems of angiogenesis, vasculogenesis, and lymphangiogenesis, and includes a brief overview of multicellular systems. We conclude with future avenues of research to guide the next generation of vascularized microfluidic models and future tissue engineered grafts.

Laser Speckle Integrated Multispectral Imaging System for In-Vivo Assessment of Diabetic Foot Ulcer Healing: A Clinical Study

The high prevalence of the world's population diagnosed with diabetes mellitus, with a significant number suffering from diabetic foot ulcer (DFU), has always been a global concern over the years. The rapid rise of this disease in the last decades is deemed increasingly alarming as it has left deleterious effects not only on affected patients but also on the society and nation. This paper aims to develop a reliable diagnostic tool to address the tremendous need for coordinated and efficient DFU management via prediction of transcutaneous oxygen saturation (StO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ) and relative blood perfusion (τ) in the affected limb. This system integrates the use of a multispectral imaging and laser speckle contrast imaging technique for two-dimensional (2D) mapping of tissue oxygen and blood perfusion level in ulcerated foot. Longitudinal study revealed a slightly higher mean StO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> and τ level in healed ulcer than in impaired healing, despite the data indicating no statistical significance between these two groups (p - value > 0.05). It was observed that a mean StO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> of at least 70 % and τ value of 1.5 (×10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> ) are necessary during the proliferative phase to ensure progressive healing. Based on these findings, this study concluded that high tissue oxygenation and perfusion levels are pivotal to ensure progressive wound healing. This work provides a rationale for evaluating the healing outcomes of skin grafting procedures in diabetic ulcers based on observation of quantitative changes in blood perfusion and tissue oxygen level during its revascularization phase.

Clinical, Hematological, Blood Gasometric and Electrolytic Changes in Dogs Receiving Whole Blood Transfusions

Background: Blood transfusion is a tool capable of saving lives. Patients undergoing blood transfusion usually present several alterations in the acid-base and electrolyte balance, aggravating the condition of critically ill patients. Some studies have demonstrated haematological alterations in certain species that received whole blood transfusions, however, few studies have evaluated acid base and electrolyte changes in dogs undergoing whole blood haemotherapy. The aim of this study was to analyze clinical, hematological, blood gas and electrolyte changes in anemic dogs after whole blood transfusion.Materials, Methods &amp; Results:Twenty nine dogs transfused due to anemia were enrolled in the study. Donors blood was collected in a transfusion bag containing citrate phosphate adenine dextrose and stored up to 24 h. Blood collections and evaluations were made before and 24 h after the transfusion. Data distribution normality was tested by the Shapiro Wilk Test. The means of the variables were compared by paired t-test. It was observed an increase in diastolic blood pressure and a reduction in heart rate (P &lt; 0.05). There was a not significant increase in systolic blood pressure, temperature, and a reduction in respiratory rate per minute. Erythrocyte, haemoglobin and haematocrit averages were significantly increased after blood transfusion (P &lt; 0.05). It was observed a reduction in the mean values of pH (P &lt; 0.05), potassium (P &gt; 0.05) and ionized calcium (P &gt; 0.05) and an increase in the mean partial pressure of carbon dioxide (pCO2) (P &lt; 0.001), bicarbonate (P &gt; 0.05) and sodium (P &lt; 0.05). The probable cause of anemia was monocytic ehrlichiosis (14/29), visceral leishmaniasis (1/29), babesiosis (1/29), co-infection of Ehrlichia canis and Leishmaniainfantum (2/19), co-infection of E. canis and Babesia vogeli (1/19). It was not possible to determine the etiology of the anemia in ten dogs. Discussion:Heart rate significantly reduced after transfusion, probably because of the increase in hematocrit, hemoglobin and erythrocyte values. It may be justified by the displacement of extravascular fluid to the intravascular space. Mean values of systolic blood pressure were slightly elevated before transfusion and remained elevated afterwards, while diastolic and mean arterial pressure increased significantly after transfusion. These changes may be due to the morbid condition and may be influenced by many other factors. Haematocrit, haemoglobin and erythrocyte values increased significantly after transfusion, according to what was observed in other studies. The significant reduction in pH and increase in pCO2 reflects the compensatory mechanism for metabolic acidosis to increase ventilation, leading to pCO2 reduction and changes in pH. The reduction in pH due to the contact of the collected blood with conservative solutions is one of the main changes thar occurs during blood storage. It was described significantly lower pH in dogs’ whole blood samples stored for more than 24h in vacutainer plastic containing CPDA-1. We may assume there was no intense pH reduction in the present study because the bags were stored for up to 24 h. Although not statistically significant, the increase of pO2 mean reflects the improvement of tissue oxygen perfusion. It was observed a significant increase in sodium ions. The mean sodium ionconcentration before transfusion was very close to the maximum reference value. Hyperkalaemia was not observed, nor was there significant reduction of potassium ions after transfusion. Several studies report hyperkalaemia and transfusion-associated cardiac arrests in humans, associated with infusion of large volumes of blood. Whole blood transfusion increased erythrogram values and did not negatively affect the electrolyte or acid-base status, representing a safe and useful tool in the intensive care of small animals.

Effects of Irinotecan on Tumor Vasculature and Oxygenation: An in vivo Study on Colorectal Cancer Model

The effects of chemotherapy on the tumor microenvironment remain poorly investigated, although these are crucial for the drug delivery and anti-tumor activity and can modify physiological behavior of cancer cells. Optical coherence angiography and phosphorescence lifetime spectroscopy are promising optical methods to characterize both tumor vasculature and its oxygenation, respectively. In this study, we used these methods to explore the influence of irinotecan, a widely used chemotherapeutic agent, on tumor angiogenesis and oxygen content in a mouse model of colorectal cancer in vivo. For the first time, it was shown that irinotecan at conventional dosing reduces tumor oxygenation and blood perfusion via antiangiogenic mechanism of action. Immunohistochemistry for hypoxia and for the endothelial cell marker CD31 verified the in vivo findings. These data show the prospects of the optical techniques to monitor tumor microenvironment in the course of chemotherapy, which can help to optimize and individualize the treatment.

Impact of RBC Transfusion on Peripheral Capillary Oxygen Saturation and Partial Pressure of Arterial Oxygen.

RBCs are known to undergo deleterious changes during storage, known as storage lesions, which have been shown to result in decreased oxygen-carrying capacity. However, there is inadequate literature describing the effects of stored RBC allogeneic transfusion on oxygen parameters in vivo. The oxygen standard parameters were retrospectively assessed before and after RBC transfusion. Patients who received 1 RBC transfusion were assessed for hemoglobin (Hb) levels, peripheral capillary oxygen saturation (Spo2), and partial pressure of arterial oxygen (Pao2) from 12 hours before and 24 hours after transfusion. In total, 78 patients who were monitored by Spo2 and 28 patients monitored by Pao2 were included in this analysis. Following RBC transfusion, Hb levels increased significantly (P < .001); however, there was a significant decrease in both Spo2 and Pao2 within 24 hours after transfusion (P = .04 and P = .003, respectively), indicating lower tissue oxygenation and lower soluble oxygen level. This single-center, retrospective study revealed evidence of significantly decreased oxygenation and tissue perfusion after single-unit RBC transfusion, despite corrected Hb levels.

Gas plasma-spurred wound healing is accompanied by regulation of focal adhesion, matrix remodeling, and tissue oxygenation

In response to injury, efficient migration of skin cells to rapidly close the wound and restore barrier function requires a range of coordinated processes in cell spreading and migration. Gas plasma technology produces therapeutic reactive species that promote skin regeneration by driving proliferation and angiogenesis. However, the underlying molecular mechanisms regulating gas plasma-aided cell adhesion and matrix remodeling essential for wound closure remain elusive. Here, we combined in vitro analyses in primary dermal fibroblasts isolated from murine skin with in vivo studies in a murine wound model to demonstrate that gas plasma treatment changed phosphorylation of signaling molecules such as focal adhesion kinase and paxillin α in adhesion-associated complexes. In addition to cell spreading and migration, gas plasma exposure affected cell surface adhesion receptors (e.g., integrinα5β1, syndecan 4), structural proteins (e.g., vinculin, talin, actin), and transcription of genes associated with differentiation markers of fibroblasts-to-myofibroblasts and epithelial-to-mesenchymal transition, cellular protrusions, fibronectin fibrillogenesis, matrix metabolism, and matrix metalloproteinase activity. Finally, we documented that gas plasma exposure increased tissue oxygenation and skin perfusion during ROS-driven wound healing. Altogether, these results provide critical insights into the molecular machinery of gas plasma-assisted wound healing mechanisms.

A novel system to collect dual pulse oximetry data for critical congenital heart disease screening research.

Access to patient medical data is critical to building a real-time data analytic pipeline for improving care providers' ability to detect, diagnose, and prognosticate diseases. Critical congenital heart disease (CCHD) is a common group of neonatal life-threatening defects that must be promptly diagnosed to minimize morbidity and mortality. CCHD can be diagnosed both prenatally and postnatally. However, despite current screening practices involving oxygen saturation analysis, timely diagnosis is missed in approximately 900 infants with CCHD annually in the USA and can benefit from increased data processing capabilities. Adding non-invasive perfusion measurements to oxygen saturation data can improve the timeliness and fidelity of CCHD diagnostics. However, real-time monitoring and interpretation of non-invasive perfusion data are currently limited. To address this challenge, we created a hardware and software architecture utilizing a Pi-top™ for collecting, visualizing, and storing dual oxygen saturation, perfusion indices, and photoplethysmography data. Data aggregation in our system is automated and all data files are coded with unique study identifiers to facilitate research purposes. Using this system, we have collected data from 190 neonates, 130 presumably without and 60 with congenital heart disease, in total comprising 1665 min of information. From these data, we are able to extract non-invasive perfusion features such as perfusion index, radiofemoral delay, and slope of systolic rise or diastolic fall. This data collection and waveform analysis is relatively inexpensive and can be used to enhance future CCHD screening algorithms.

Modern experience in conducting cerebral oximetry in neonatology: review

Annotation. Near-infrared spectroscopy (NIRS), non-invasive monitoring of tissue oxygenation in many organs, has potentially high diagnostic and prognostic value in critically ill patients. Aim – to analyze modern scientific data on cerebral oximetry by near infrared spectroscopy in neonatal practice. A selective review of literature science data on Internet databases: Pub Med, UpToDate, Medscape EU and Pediatrics was carried out in retrospect. It has been established that understanding neonatal brain oxygenation may be of great clinical importance, since most neonatal pathology is associated with the brain. Vital monitoring provides important information about the infant's health, but does not offer direct information about oxygenation and brain perfusion. Monitoring brain oxygenation with NIRS, at least during the vulnerable transition period during the first 3 days after birth, provides the clinician with additional important information. It can guide clinical management to prevent brain injury and prevent unnecessary treatment, and can provide important information about the infant’s prognosis. Thus, NIRS is a promising non-invasive technology that provides continuous monitoring of neonatal oxygenation parameters. Significant limitations of the method are the difficulties in the clinical interpretation of regional oxygenation indices, the lack of large-scale studies to determine the normative values of regional oxygenation in newborns and to identify reliable prognostic indicators in violation of regional blood circulation. It is reasonable to expect the results of further research.

Do Pre-Operative Transcutaneous Oxygen Perfusion Measurements Predict Atraumatic Major Lower Extremity Amputation Wound Healing?

Category:OtherIntroduction/Purpose:Determining appropriate amputation level is a challenging task requiring clinical, laboratory, and imaging data. However, there is no validated consensus on the method with the most prognostic accuracy. Transcutaneous oxygen perfusion measurement (TcPO2) is a noninvasive means of measuring tissue oxygenation. A TcPO2 > 30-40mm Hg is widely cited as a positive predictor of post-operative wound healing, but its validity has not been well defined. We hypothesized that TcPO2 levels positively correlate with the success of amputation wound healing. Additionally, we secondarily investigated the correlation between other preoperative demographics and clinical variables and their impact on post-operative amputation wound healing.Methods:A retrospective chart review was performed on patients who underwent lower extremity above, through, or below knee amputations at a single institution with documented preoperative TcPO2 values between January 1, 2012 and December 1, 2018 and a minimum 30 days post-operative clinical follow up. Amputations performed for oncologic pathology, infected arthroplasty, osteomyelitis and traumatic amputations were excluded in order to isolate TcPO2 as a decision-making test for amputation level. This yielded one hundred and forty-one total amputations. Of these ninety-three were below knee amputations (BKA), six through knee amputations, and forty-two above knee amputations (AKA). Chi-square and t-tests were used to compare successful and failed amputations where appropriate.Results:Eighty-six of the amputations were successful and fifty-five failed, as defined by post-operative wound dehiscence or infection. Of these, thirty-seven were BKAs, four were through knee amputations and fourteen were AKAs. There was a significant difference in preoperative TcPO2 levels between the successful and failure groups at 46.2 and 38.3 respectively (p = 0.02). A TcPO2 of 30-40mm Hg had a success rate of 68.8%, and a TcPO2 < 20mm Hg a success rate of 18.2%. A receiver operating characteristic curve for TcPO2 levels predicting amputation success elucidated that with an area under the curve of 0.53 for the AKA cohort and 0.61 for the BKA cohort, the diagnostic ability is far from prognostic.Conclusion:Our results provide new insight into the predictive accuracy of preoperative TcPO2 levels. There is not a linear association between TcPO2 and success rate. A TcPO2 < 20mm Hg has a high positive predictive value for failure, but higher TcPO2 levels are not 100% predictive of amputation wound healing as reported by prior studies. Multiple factors should be considered when selecting amputation level.

Neuroprotection of hypoxic/ischemic preconditioning in neonatal brain with hypoxic-ischemic injury.

The neonatal brain is susceptible to hypoxic-ischemic injury due to its developmental characteristics. Hypoxia-ischemia means a decreased perfusion of oxygen and glucose, which can lead to severe encephalopathy. Although early initiation of therapeutic hypothermia was reported to provide neuroprotection for infants after HI, hypothermia administered alone after the acute insult cannot reverse the severe damage that already has occurred or improve the prognosis of severe hypoxic-ischemic encephalopathy. Therefore, exploring new protective mechanisms for treating hypoxic-ischemic brain damage are imperative. Until now, many studies reported the neuroprotective mechanisms of hypoxic/ischemic preconditioning in protecting the hypoxic-ischemic newborn brains. After hypoxia and ischemia, hypoxia-inducible factor signaling pathway is involved in the transcriptional regulation of many genes and is also play a number of different roles in protecting brains during hypoxic/ischemic preconditioning. Hypoxic/ischemic preconditioning could protect neonatal brain by several mechanisms, including vascular regulation, anti-apoptosis, anti-oxidation, suppression of excitotoxicity, immune regulation, hormone levels regulation, and promote cell proliferation. This review focused on the protective mechanisms underlying hypoxic/ischemic preconditioning for neonatal brain after hypoxia-ischemia and emphasized on the important roles of hypoxia inducible factor 1 signaling pathway.

LUNG TRANSPLANT PROGRAMS IN DEVELOPING COUNTRIES: CHALLENGES AND SOLUTIONS

Introduction: The overwhelming majority of lung transplants (LT) performed are in developed countries of Europe and North America. In contrast, little is known about the current status of LT in developing nations. The objective is to summarize the unique challenges and present potential solutions for starting a new LT program in a developing country such as, ours in Vietnam. We hope this review will guide healthcare providers in developing countries who are contemplating embarking on such journey. Materials and Methods: For this review, studies were identified by searching the electronic database PubMed using keyword “lung transplantation” published within the past five years. To be included in this review, articles needed to be original, involving human studies, and published by programs from developing countries. Overall, we identified 25 papers that are included in our review. They are from 10 countries including Argentina, Brazil, Chile, China, Colombia, India, Iran, Korea, Turkey and Vietnam. Results and Discussion: The key challenges that programs in developing countries encountered included shortage and marginal quality of donated organs, lack of dedicated multi-disciplinary LT team, limited availability of advanced technology such as extracorporeal membrane oxygenation or ex-vivo lung perfusion and high risk of post-transplant infections. Education and collaboration among government, public, and healthcare sectors was seen as fundamental to building and maintaining a successful program. Despite minimal resources and the challenges above, LT survival rates in developing countries improved and were comparable with outcomes reported by the International Society for Heart and Lung Transplantation Registry. Conclusion: Starting a new LT program is a daunting task that is complex and resource intensive, regardless of geography, and is even more so in developing countries. But it is feasible if all stakeholders allocate appropriate resources to develop dedicated, qualified multi-disciplinary LT healthcare teams, establish a nationwide network of organ sharing, as well as raise public awareness about the importance of organ donation. Ngoc TB Nguyen. Nghia V Nguyen. Vinh L Nguyen.

Association between tissue hypoxia, perfusion restrictions, and microvascular architecture alterations with lesion-induced impairment of neurovascular coupling

Functional magnetic resonance imaging (fMRI) has been mainly utilized for the preoperative localization of eloquent cortical areas. However, lesion-induced impairment of neurovascular coupling (NVC) in the lesion border zone may lead to false-negative fMRI results. The purpose of this study was to determine physiological factors impacting the NVC. Twenty patients suffering from brain lesions were preoperatively examined using multimodal neuroimaging including fMRI, magnetoencephalography (MEG) during language or sensorimotor tasks (depending on lesion location), and a novel physiologic MRI approach for the combined quantification of oxygen metabolism, perfusion state, and microvascular architecture. Congruence of brain activity patterns between fMRI and MEG were found in 13 patients. In contrast, we observed missing fMRI activity in perilesional cortex that demonstrated MEG activity in seven patients, which was interpreted as lesion-induced impairment of NVC. In these brain regions with impaired NVC, physiologic MRI revealed significant brain tissue hypoxia, as well as significantly decreased macro- and microvascular perfusion and microvascular architecture. We demonstrated that perilesional hypoxia with reduced vascular perfusion and architecture is associated with lesion-induced impairment of NVC. Our physiologic MRI approach is a clinically applicable method for preoperative risk assessment for the presence of false-negative fMRI results and may prevent severe postoperative functional deficits.