Mesoscopic Mapping of Ictal Neurovascular Coupling in Awake Behaving Mice Using Optical Spectroscopy and Genetically Encoded Calcium Indicators

Unambiguously identifying an epileptic focus with high spatial resolution is a challenge, especially when no anatomic abnormality can be detected. Neurovascular coupling (NVC)-based brain mapping techniques are often applied in the clinic despite a poor understanding of ictal NVC mechanisms, derived primarily from recordings in anesthetized animals with limited spatial sampling of the ictal core. In this study, we used simultaneous wide-field mesoscopic imaging of GCamp6f and intrinsic optical signals (IOS) to record the neuronal and hemodynamic changes during acute ictal events in awake, behaving mice. Similar signals in isoflurane-anesthetized mice were compared to highlight the unique characteristics of the awake condition. In awake animals, seizures were more focal at the onset but more likely to propagate to the contralateral hemisphere. The HbT signal, derived from an increase in cerebral blood volume (CBV), was more intense in awake mice. As a result, the “epileptic dip” in hemoglobin oxygenation became inconsistent and unreliable as a mapping signal. Our data indicate that CBV-based imaging techniques should be more accurate than blood oxygen level dependent (BOLD)-based imaging techniques for seizure mapping in awake behaving animals.

Oxygen Homeostasis and Mitochondrial Function in COVID-19 and ARDS Patients: The Ultimate Vital Signs

The leading cause of death from the COVID-19 is the development of Pneumonia and Acute Respiratory Distress Syndrome-ARDS. Advanced physiological monitoring of COVID -19 patients in real time is a missing tool that avoid the optimization of better diagnosis and evaluating the efficacy of the treatment given. As of today, the monitoring of the systemic vital signs provides important information regarding the respiratory and cardiovascular systems including the pulse oximetry that provide data on hemoglobin oxygenation in the macro circulation. Our hypothesis is that the pathophysiology of COVID-19 and ARDS patients includes severe changes in the microcirculatory hemodynamics and cellular disturbances in Tissue and cellular Oxygen Homeostasis. Therefore, we postulate that real time monitoring of mitochondrial NADH redox state and microcirculatory blood flow, volume and hemoglobin oxygenation is the missing information that will affect dramatically the outcome of COVID-19 and ARDS patients. During the last 2 decades we studied the mechanism of blood flow redistribution activated in animal models as well as in patients exposed to total body negative oxygen balance. This mechanism is activated by the sympathetic pathway. This effect is not equal in all organs of the body, namely, in the most vital organs - brain, heart, and adrenal glands oxygen supply is preserved while in the less vital organs (visceral and peripheral organs) hypo perfusion and negative oxygen balance is recorded. In order to evaluate the tissue oxygen homeostasis, we developed a new concept named - LifenLight Score (LLS)TM based on the monitoring of four physiological parameters measured in real time from one of the less vital organs in the body. Our developed device is monitoring mitochondrial function by measuring the NADH auto fluorescence and microcirculatory blood flow, tissue reflectance and hemoglobin oxygenation. In animal model we monitored simultaneously the brain and the small intestine. In patients we used a 3-way Foley catheter introduced to the bladder via the urethra. We found that monitoring the less vital organ could serve as an early warning signal to the development of negative oxygen balance in the body as well as indicate of a recovery process in the improvement of the oxygen balance homeostasis. In conclusion, we hypothesize that using our new monitoring system will be able to detect deterioration process related to hypoxia in COVID-19 and ARDS patients, as well as to monitor improvement in tissue oxygen balance due to various treatments such as exposure to hyperoxia.

Methemoglobinemia – A review and recommendation for management – Acute methemoglobinemia with hemolytic anemia following suicidal use of aniline based substance

Methemoglobinemia is a rare disease classification related with congenital or acquired (usually iatrogenic) hemoglobin oxygenation disorder. Despite the fact that number of potentially methemoglobin forming agents is very long, methemoglobinemia is still a case-report of patients admitting to the Emergency Departments. The patient was brought after consuming resin hardener for suicidal purposes from the Center of lower reference to the hospital Emergency Department with suspected burns of the gastrointestinal tract. The patient presented cyanosis, dyspnoea and brown-colored urine on admission.

Optimal Partitioning Method for Evaluating of Effect of Hemoglobin Oxygenation Levels of Vessel Endothelial Growth Factor

The work is aimed to study relationship between vessel endothelial growth factor (VEGF) serum levels and hypoxia in patients with severe neurological disorders. Overviewed literature sources indicate activation of VEGF synthesis during hypoxia. But standard correlation analysis does not reveal a statistically significant association between VEGF levels and pulse oxymetry parameters objectively assessing oxygen supply. Due to a proposed in the paper technique it became possible to reveal valid relationship between VEGF levels and oxygenation. This relationship can be described as increase of correlation between VEGF and immunological complement C4 when oxygenation level is below a certain threshold. Developed method includes searching of such boundaries for oxymetry parameters that correlation coefficients between VEGF and some additional factor Z in formed group are maximally different. ranges. The original technique based on permutation test was used not only to asses validity of effects associated with each oxymetry parameter but also to evaluate joint effect by full group of such factors. Great number of variable from database were tested as additional factors. So additional correction of validity was made to take into account multiple testing.

Hyperspectral imaging as a possible tool for visualization of changes in hemoglobin oxygenation in patients with deficient hemodynamics – proof of concept

There is a lack of imaging tools for the evaluation of spatial alterations in microcirculation including blood oxygen saturation and hemoglobin distribution but recent innovative developments in hyperspectral technology may offer a solution. We examined different hemodynamic disorders in patients suffering from scleroderma, Dupuytren surgery, chronic foot ulcera and skin infections. Superficial and deeper blood oxygen saturation, hemoglobin distribution and water content were determined using hyperspectral imaging (HSI). In the patient with scleroderma, distinct cutaneous low perfused regions correlated with macroscopic skin aspects and seem to be potential therapy control marker. With HSI accurate clinical evaluation of a macroscopic conspicuous wound after Dupuytren surgery was possible and influenced further surveillance decisions. HSI clearly revealed the spatial geometry and also the clinically related perfusion parameters of abscess formation and chronic ulcer wounds. The hemodynamically relevant parameters like blood oxygen saturation (1 mm to approx. 6 mm subcutaneous), total hemoglobin distribution and tissue water content can be easily determined and visualized with HSI in near real time. Hence, this technique seems to be suitable for routine diagnostics of acute and chronic wounds as well as for the examination of systemic hemodynamic disturbances. Special indications may be transplant surveillance and monitoring of therapeutical interventions.

Pulmo uterinus: a history of ideas on fetal respiration

Theories about fetal respiration began in antiquity. Aristotle characterized pneuma as warm air, but also as the enabler of vital functions and instrument of the soul. In Galen’s system of physiology, the vital spirit was carried by the umbilical arteries, the nutrients by the umbilical vein from the placenta to the fetus. In 1569 Aranzio postulated that the maternal and fetal vasculatures are distinct. From 1670 to 1690, a century before the discovery of oxygen, researchers understood that during respiration some form of exchange with the air must occur, naming the substance biolychnium, phlogiston, sal-nitro, or nitro-aerial particles. An analogy of placental and pulmonary gas exchange was described in 1674 by Mayow. In 1779, Lavoisier understood the discovery of oxygen, discarded the phlogiston theory, and based respiration physiology on gas exchange. With the invention of the spectroscope, it became possible to measure hemoglobin oxygenation, and in 1876 Zweifel proved fetal oxygen uptake. Major progress in understanding fetal gas exchange was achieved in the 20th century by the physiologists Barcroft in Cambridge and Dawes in Oxford.

Manipulating hemoglobin oxygenation using silica nanoparticles: a novel prospect for artificial oxygen carriers

Key Points Silica nanoparticles act as an effector for human native and sickle cell hemoglobin while preserving their tetrameric structure. Manipulating hemoglobin oxygenation using nanoparticles opens the way for the rational design of hemoglobin-based oxygen carriers.