Tissue Hypoxia
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2021 ◽  
Vol 118 (25) ◽  
pp. e2025236118
Romain Enjalbert ◽  
David Hardman ◽  
Timm Krüger ◽  
Miguel O. Bernabeu

The tumor microenvironment is abnormal and associated with tumor tissue hypoxia, immunosuppression, and poor response to treatment. One important abnormality present in tumors is vessel compression. Vessel decompression has been shown to increase survival rates in animal models via enhanced and more homogeneous oxygenation. However, our knowledge of the biophysical mechanisms linking tumor decompression to improved tumor oxygenation is limited. In this study, we propose a computational model to investigate the impact of vessel compression on red blood cell (RBC) dynamics in tumor vascular networks. Our results demonstrate that vessel compression can alter RBC partitioning at bifurcations in a hematocrit-dependent and flow rate–independent manner. We identify RBC focusing due to cross-streamline migration as the mechanism responsible and characterize the spatiotemporal recovery dynamics controlling downstream partitioning. Based on this knowledge, we formulate a reduced-order model that will help future research to elucidate how these effects propagate at a whole vascular network level. These findings contribute to the mechanistic understanding of hemodilution in tumor vascular networks and oxygen homogenization following pharmacological solid tumor decompression.

2021 ◽  
Matyas Kovacs ◽  
Lorenzo Peluso ◽  
Hassane Njimi ◽  
Olivier Dewitte ◽  
Elisa Bogossian ◽  

Abstract BackgroundAlthough increasing cerebral perfusion pressure (CPP) is commonly accepted to improve brain tissue oxygen pressure (PbtO2), it remains unclear whether recommended CPP targets (i.e. > 60 mmHg) would result in adequate brain oxygenation in brain injured patients. The aim of this study was to identify the target of CPP associated with normal brain oxygenation. MethodsProspectively collected data including patients suffering from acute brain injury and monitored with PbtO2, in whom daily CPP challenge using vasopressors was performed. Initial CPP targets were >60 mmHg; norepinephrine infusion was modified to have an increase in CPP of at least 10 mmHg at two different steps above the baseline values. Whenever possible, the same CPP challenge was performed for the following days, for a maximum of 5 days. CPP “responders” were patients with a relative increase in PbtO2 from baseline values >20%.ResultsA total of 53 patients were included. On the first day of assessment, CPP was progressively increased from 73 [70-76] to 83 [80-86] and 92 [90-96] mmHg, which resulted into a significant PbtO2 increase (from 20 [17-23] mmHg to 22 [20-24] mmHg and 24 [22-26] mmHg, respectively; p<0.001). Median CPP value corresponding to PbtO2 values > 20 mmHg was 79 [74-87] mmHg, with 2 (4%) patients who never achieved such target. Similar results of CPP targets were observed the following days. A total of 25 (47%) were PbtO2 responders during the CPP challenge on day 1, in particular if low PbtO2 was observed at baseline. ConclusionsPbtO2 monitoring can be an effective way to individualize CPP values to avoid tissue hypoxia. Low PbtO2 values at baseline can identify the responders to the CPP challenge.

Constantinos Pantos ◽  
Vassiliki Apostolaki ◽  
Leonidas Kokkinos ◽  
Athanassios Trikas ◽  
Iordanis Mourouzis

Sepsis and septic shock result in impaired microcirculation and red blood cell rheology which lead to tissue hypoxia and multi-organ failure. Early administration of triiodothyronine prevents tissue hypoxia in experimental sepsis. In this context, a clinical trial was initiated to test the efficacy of acute triiodothyronine administration to combat tissue hypoxia in critically ill COVID19 patients. Here, we provide preliminary data from interim analysis of this study showing a novel acute effect of triiodothyronine on erythrocyte sedimentation rate which may have an important therapeutic impact on red blood cell rheology and tissue hypoxia in sepsis and particular in COVID19 critical illness. Trial registration: ClinicalTrials.gov, NCT04348513. Registered 16 April 2020, https://clinicaltrials.gov/ct2/show/NCT04348513

2021 ◽  
Moataz Dowaidar

Tissue hypoxia has been found as a master regulator of alternative splicing, which can have significant clinical implications. Hypoxia-elicited AS is more common in the setting of various cancer hallmarks than other illnesses, owing to the fact that hypoxia and AS are intensively explored in cancer. However, an increasing number of hypoxia-induced AS episodes have been linked to a variety of clinical conditions, including neurological and cardiovascular disorders. Hypoxia-induced AS, of course, has its own set of markers with prognostic and therapeutic implications. Targeted regulation of hypoxia signaling with the objective of modulating hypoxia-driven AS is of great interest in some cancers. In order to design acceptable therapeutic paradigms, future research will be necessary to unravel the proper molecular pathways. Although some of the discovered molecular targets appear to have therapeutic potential, more in-vivo research is required.

2021 ◽  
Vol 13 (2) ◽  
Jacob Fuqua ◽  
Josephine Reece ◽  
Sarah Sofka

Secondary polycythemia (SP) occurs as a result of increase erythropoietin levels most commonly as a result of tissue hypoxia. Symptoms such as erythromelalgia, pruritis, and bleeding, which are frequently seen in polycythemia vera (PV), do not commonly occur in SP. Phlebotomy is considered one of the mainstays of therapy for PV but is rarely used for treatment of SP due to concern about worsening tissue hypoxia. We present the case of a patient with severe SP due to chronic hypoxic lung disease who presented with erythromelalgia, pruritis, and bleeding and was treated successfully with therapeutic phlebotomy. This case illustrates the importance of considering the use of therapeutic phlebotomy in symptomatic patients with severe SP.

Ronald F. Coburn

The major goal of this article was to quantify relationships of the carboxyhemoglobin % saturation, a calculated tissue PCO and tissue hypoxia to the binding of carbon monoxide (CO) to canine skeletal and heart ventricular muscle extravascular (EV) tissue under normal conditions and during CO poisoning scenarios. These data are relevant to CO poisoning because CO bound to EV cellular hemoproteins evoke metabolic changes that produce toxic effects. Skeletal and heart muscle EV CO contents were calculated from data obtained from biopsies performed on living anesthetized dogs reported in previous publications (4, 6). Results include normal values of EV CO contents of resting skeletal muscle and heart ventricular muscle, effects of increasing COHb% saturation and a calculated mean tissue PCO on skeletal muscle EV CO binding, and effects of tissue hypoxia evoked by arterial hypoxemia on EV CO binding in both of these tissues. This study is the first that shows that tissue hypoxia-induced CO shifts out of blood resulting in increased EV CO binding are a mechanism that causes CO toxicity. Projections of results to tissue PCO levels occurring during different severe CO toxicity scenarios predict that skeletal muscle EV CO contents could increase as much as 100 to 300 fold.

EMJ Diabetes ◽  
2021 ◽  
Yigit Akduman ◽  
William Anderson ◽  
Sandeep Saxena

COVID-19 is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has been shown to affect a multitude of organ systems. It is often associated with vasculitis or thromboembolic disease with resultant tissue hypoxia. This report presents a case of fast progression diabetic retinopathy in the case of a SARS-CoV-2 infection. The findings conclude that patients with diabetes should be more frequently monitored for emergence or progression of diabetic retinopathy if they present with COVID-19.

2021 ◽  
Vol 11 (1) ◽  
Jihad Mallat ◽  
Benoit Vallet

AbstractThe purpose of the study was to evaluate the behavior of the venous-to-arterial CO2 tension difference (ΔPCO2) over the arterial-to-venous oxygen content difference (ΔO2) ratio (ΔPCO2/ΔO2) and the difference between venous-to-arterial CO2 content calculated with the Douglas’ equation (ΔCCO2D) over ΔO2 ratio (ΔCCO2D/ΔO2) and their abilities to reflect the occurrence of anaerobic metabolism in two experimental models of tissue hypoxia: ischemic hypoxia (IH) and hypoxic hypoxia (HH). We also aimed to assess the influence of metabolic acidosis and Haldane effects on the PCO2/CO2 content relationship. In a vascularly isolated, innervated dog hindlimb perfused with a pump-membrane oxygenator system, the oxygen delivery (DO2) was lowered in a stepwise manner to decrease it beyond critical DO2 (DO2crit) by lowering either arterial PO2 (HH-model) or flow (IH-model). Twelve anesthetized and mechanically ventilated dogs were studied, 6 in each model. Limb DO2, oxygen consumption ($${\dot{\text{V}}\text{O}}_{2}$$ V ˙ O 2 ), ΔPCO2/ΔO2, and ΔCCO2D/ΔO2 were obtained every 15 min. Beyond DO2crit, $${\dot{\text{V}}\text{O}}_{2}$$ V ˙ O 2 decreased, indicating dysoxia. ΔPCO2/ΔO2, and ΔCCO2D/ΔO2 increased significantly only after reaching DO2crit in both models. At DO2crit, ΔPCO2/ΔO2 was significantly higher in the HH-model than in the IH-model (1.82 ± 0.09 vs. 1.39 ± 0.06, p = 0.002). At DO2crit, ΔCCO2D/ΔO2 was not significantly different between the two groups (0.87 ± 0.05 for IH vs. 1.01 ± 0.06 for HH, p = 0.09). Below DO2crit, we observed a discrepancy between the behavior of the two indices. In both models, ΔPCO2/ΔO2 continued to increase significantly (higher in the HH-model), whereas ΔCCO2D/ΔO2 tended to decrease to become not significantly different from its baseline in the IH-model. Metabolic acidosis significantly influenced the PCO2/CO2 content relationship, but not the Haldane effect. ΔPCO2/ΔO2 was able to depict the occurrence of anaerobic metabolism in both tissue hypoxia models. However, at very low DO2 values, ΔPCO2/ΔO2 did not only reflect the ongoing anaerobic metabolism; it was confounded by the effects of metabolic acidosis on the CO2–hemoglobin dissociation curve, and then it should be interpreted with caution.

2021 ◽  
Vol 66 (1-2) ◽  
pp. 65-74
Yu. Р. Orlov ◽  
V. V. Afanasyev ◽  
I. A. Khilenko

The aim of the work was the search for materials from experimental and clinical studies reflecting the pathogenetic role of the possible use of succinates for the correction of hypoxia in COVID-19. Materials and methods. 79 foreign and domestic literature sources were analyzed concerning the pathogenesis of COVID-19 and the pathogenetic role of succinates in hypoxia under conditions of COVID-19, oxidative stress, and diaphragmatic dysfunction were analyzed. The literature search was carried out using Pubmed and ELIBRARY.ru databases. Results. As the analysis of the literature has shown, tissue hypoxia is the basis of COVID-19 pathogenesis, triggering the entire cascade of  pathomorphological events leading to the development of multiple organ failure. A number of experimental and clinical studies (on a fairly large number of patients) reflect the positive effect of tissue hypoxia correction using succinates, both in adult patients and in children with a different spectrum of pathology associated with acute respiratory failure syndrome. Conclusion. Analysis of literature data allows to substantiate the prospect of using preparations containing succinate (reamberin, cytoflavin) in the complex therapy of severe cases of COVID-19. 

Moumita Mondal ◽  
Sankari Santra ◽  
Rajat Choudhuri ◽  
Amartya Das

Background: Post-operative microcirculatory alteration causes hypoperfusion, tissue hypoxia and organ dysfunction, resulting in significant morbidity and mortality. Increase in serum lactate level in response to tissue hypoxia may serve as a cost effective tool to assess status of all organ dysfunction being sensitive but not organ specific and may help in early prognostication. Aim of this study was to investigate the association of blood lactate levels during the first 24 hours after surgery with postoperative morbidity and mortality, with length of ITU stay and to correlate the lactate values at various time points with different postoperative complications (POC).Methods: 150 patients undergoing elective abdominal surgery were included. Blood lactate (mmol/lit) levels were measured immediately on admission to the Intensive Therapy Unit (ITU) and at 6, 12, and 24 hours of admission. The parameters of clinical outcome included were mortality, shock, Acute kidney injury (AKI), respiratory failure, wound dehiscence and length of ITU stay. Heart Rate, Mean Arterial Pressure, spo2, Temperature and Urine output were also measured.Results: There was statistically significant difference in the lactate levels measured at the above mentioned point of time (0, 6, 12 and 24h) in cases with death and without fatal outcome, with and without respiratory failure, with and without AKI, with and without shock and in cases with and without wound dehiscence (p<0.05). There was a statistically significant difference in urine output, duration of ITU stay and duration of intubation (p<0.05).Conclusions: Increased serum lactate levels were significantly associated with postoperative complications, mortality and length of ITU stay in patients undergoing major elective abdominal surgery.

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