Blood Oxygen Tension Research Articles

Choice of an artificial lung ventilation technique for the correction of mitral valve pathology from a mini-thoracotomy approach

Background. In recent years, there has been a growing number of cardiac surgeries performed using minimally invasive techniques. However, there is still debate about the optimal ventilation support for these operations, which are performed through a mini-thoracotomy.The objective was to study the possibility of using high-frequency jet ventilation during minimally invasive mitral valve surgery performed from right-sided mini-thoracotomy, to evaluate its effectiveness and safety.Materials and methods. 80 patients were divided into two groups: one group received high-frequency jet ventilation (HFJV), and the other received low-volume ventilation (LVV). Before surgery, during surgery, and in the intensive care unit, invasive hemodynamic parameters, arterial blood gas composition, and metabolic markers were assessed. The nature and incidence of postoperative complications were also analyzed.Results. In the HFJV group, compared to the LVV group, the level of oxygen tension in arterial blood (PaO2) was significantly higher at 30 minutes after thoracotomy – 307 (220–352) mmHg versus 106 (90–127.5) mmHg, p < 0.001, and at 30 minutes after the end of cardiopulmonary bypass (CPB) – 264 (188–323) mmHg versus 147 (109.5–183.5) mmHg, p < 0.001. PaO2/FiO2 was also higher in the HFJV group compared to the LVV group at these stages – 623 (450–714) versus 214 (171.3–263.3), p < 0.001 and 534 (367–654) versus 260 (200.5 – 358), p < 0.001. The number of patients with a PaO2/FiO2 of 200 or lower in the HFJV group was significantly lower than in the LVV group – 2.5 % compared to 32 %, p < 0,001 before CPB and 5 % compared to 25 %, р = 0,013 after CPB.There was no statistically significant difference between the groups in the number of postoperative pulmonary complications, as well as the duration of artificial lung ventilation (ALV) and stay in the intensive care unit (ICU).Conclusions. The use of high-frequency jet ventilation during minimally invasive mitral valve surgery performed through right-sided mini-thoracotomy provides adequate oxygenation and prevents the development of hypoxemia. This technique does not increase the number of postoperative complications.

Effects of Remimazolam With or Without Remifentanil on Oral Tissue Blood Flow and Oxygen Tension in Rabbits

Objective To clarify the effects of remifentanil and remimazolam on the cardiovascular system, oral tissue blood flow, and oral tissue oxygen tension during general anesthesia in rabbits. Methods Male Japanese white rabbits (body weight, 2.5 kg; N = 11) were treated with remimazolam at a dose of 1 mg/kg/h continuously. Measurements included blood pressure, heart rate, tissue blood flow (common carotid artery, tongue mucosal, mandibular bone marrow and masseter muscle), and tissue oxygen tension (mandibular bone marrow and masseter muscle). Remifentanil was then administered at 0.2 μg/kg/min and each measurement was collected again. The dose of remifentanil was increased to 0.4 μg/kg/min and each measurement was collected again. The same measurements were collected when remimazolam was administered at doses of 2 mg/kg/h and 4 mg/kg/h. Results Remimazolam administration did not significantly alter the parameters of each observation. Blood pressure, heart rate, and tissue blood flow (common carotid artery, tongue mucosal, mandibular bone marrow, and masseter muscle) decreased significantly in a dose-rate dependent manner under remifentanil administration, whereas tissue oxygen tensions (mandibular bone marrow and masseter muscle) were maintained. Conclusion Remimazolam anesthesia in rabbits had minimal effects, but in combination with remifentanil, it produced remifentanil dose-dependent decreases in oral tissue blood flow as well as blood pressure and heart rate.

Is hyperoxia in early pediatric veno-veno extracorporeal life support associated with mortality?

Background: Data is limited regarding the effects of supraphysiologic blood oxygen tension (hyperoxia) in patients requiring extracorporeal life support (ECLS). We sought to evaluate the association between hyperoxia and outcomes in pediatric patients requiring veno-venous (VV) ECLS. Methods: Retrospective single-center study at an academic children’s hospital, Children’s Healthcare of Atlanta, Emory University School of Medicine that included all patients 0–18 years who required VV-ECLS between 01/2014 and 12/2019. Results: During the study period 110 VV-ECLS runs occurred in 110 patients. Using a receiver operating characteristic curve, a mean partial pressures of oxygen (PaO2) of 122 mmHg in the first 48 hours of ECLS was determined to have the optimal discriminatory ability with regard to mortality (sensitivity 41% and specificity 86%). Of the VV-ECLS runs, 68 (61.8%) had PaO2 > 122 mmHg (hyperoxia group). The hyperoxia group tended to be older (105.4 vs. 1.6 months, p = 0.001), had higher rates of hemorrhagic complications (69.6% vs. 25.3%, p = 0.0001), and higher mortality rate (57.9% vs. 19.5%, p = 0.002). Adjusting for confounders, the hyperoxia group had higher odds of mortality (OR: 7.97, 95% CI: 1.72–36.86, p = 0.0079). Conclusion: Children exposed to hyperoxia during the first 48 h of VV-ECLS were 8 times more likely to die than those who were not after adjusting for confounders (age group, body surface area, and indication for ECLS). Multicenter and prospective evaluation of this modifiable risk factor is imperative to improving the care of this high-risk cohort.

Is Hyperoxia During Veno-Arterial Extracorporeal Life Support Due to Cardiopulmonary Failure Associated with Mortality in Pediatric Patients?

Background Data is limited regarding the effects of supraphysiologic blood oxygen tension in patients requiring extracorporeal life support (ECLS). We sought to evaluate the association between hyperoxia and outcomes in pediatric patients requiring veno-arterial (VA) ECLS. Methods Retrospective single-center study at an academic children’s hospital that included all patients 0–18 years who required VA-ECLS between 01/2014–12/2019. Results: During the study period, 229 VA-ECLS runs occurred in 229 patients. The majority of patients were neonates (73.4%) with cardiac being the most common indication (48.9%). The median time from admission to cannulation was 78.5 hours (IQR 14, 356) with a median ECLS duration of 111.5 hours (IQR 65.5, 184.5). Overall mortality rate was 44.5%. Using a receiver operating curve, a mean PaO2 of 233 mmHg in the first 48-hours of ECLS was determined to have the optimal discriminatory ability for mortality (sensitivity 36% and specificity 76%). Of the VA-ECLS cohort, 68 (29.7%) had mean PaO2 > 233 mmHg (hyperoxia group). The hyperoxia group tended to be older (median age 4.6 vs 1.5 months, p=0.019), had a primary cardiac indication for VA-ECLS (60% vs 44%, p=0.0004), and had higher mortality rate (54% vs 40%, p=0.050). In the multivariable analysis, after adjusting for covariables, the data demonstrated increased odds of mortality (aOR 2.02, 95% CI 1.03, 3.97, p=0.03). The odds of development of stage II or III acute kidney injury (AKI) (aOR 2.04, 95% CI 0.82, 5.50) but that did not reach statistical significance (p=0.120), Conclusion There is evidence that hyperoxia during the first 48-hours of VA-ECLS may be associated with mortality and development of acute kidney injury, although this did not reach statistical significance. Multicenter and prospective evaluation of this modifiable risk factor is imperative to improve the care of this high-risk cohort.

THE INFLUENCE OF BIOCOMPATIBILITY OF THE EXTRACORPOREAL OXYGENATOR CIRCUIT ON THE DEGREE OF HEMOLYSIS AND OPTIMIZATION OF OXYGEN STATUS IN MINIMALLY INVASIVE CORONARY ARTERY BYPASS GRAFTING

Introduction. A distinctive feature of cardiopulmonary bypass in minimally invasive coronary artery bypass grafting (CABG) is the significantly longer perfusion time, involving active blood drainage from the vein to the cardiotomy reservoir, which carries the risk of hemolysis development. In this context, mechanical hemolysis disrupts the gas transport function of the blood. The aim of the research. Reducing hemolysis and optimizing oxygen status of patients during minimally invasive coronary artery bypass grafting surgeries. Materials and methods. The study included 60 patients, who underwent minimally invasive coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) under moderate hypothermia. The patients were divided into two groups of 30 individuals each. To improve the biocompatibility of the oxygenator, the circuit in Group 1 (Gr1) was treated with an adaptive composition, while in Group 2 (Gr2), the oxygenator circuit remained untreated. The following parameters were examined: hemoglobin (Hb), hematocrit (Ht), red blood cell count (RBC), oxygen delivery index (DO2I), oxygen consumption index (VO2I), oxygen extraction ratio (O2ER%), oxygen extraction index (O2EI%), venous (SpvO2), and arterial (SpaO2) oxygen saturation, oxygen tension in arterial (PaO2) and venous blood (PvO2), acid-base status of the blood (pH, pCO2,HCO3ˉ, BE), and the degree of hemolysis. Results. Before initiation of cardiopulmonary bypass (CPB), an insignificant increase in O2IE% was observed in Gr1 (26.07±1.57) and Gr2 (27.11±0.81); p=0.875, indicating an increase in tissue oxygen consumption. At the hypothermic stage CPB, both Gr1 and Gr2 demonstrated a statistically significant decrease in Hb, Ht, and RBC levels (p<0.05) due to hemodilution, accompanied by a decrease in IDO2, IVO2, O2IE%, and O2ER% in both groups due to hypothermia. After rewarming, O2ER% in Gr1 (22.91±2.68) and Gr2 (24.59±2.02); p=0.191, and O2EI% in Gr1 (22.92±2.44) and Gr2 (24.61±2.01); p=0.215, were in the normal range. After weaning off cardiopulmonary bypassin Gr2, O2EI% was 27.34±1.97, indicating an increase in oxygen consumption and oxygen extraction. Upon separation from CPB, Gr2 showed a tendency to mild compensated metabolic acidosis, mainly due to HCO3ˉ 21.9±0.3. During the rewarming stage, the hemolysis value was 0.36±0.09in Gr1 and 0.45±0.17 in Gr2 (p<0.001). After CPB, hemolysis was 0.41±0.15 in Gr1 and 0.61±0.22 in Gr2 (p<0.001). Conclusions. Improving the biocompatibility of the extracorporeal oxygenatorcircuit makes it possible to reduce hemolysis and optimise the patient's oxygen status after cardiopulmonary bypass in minimally invasive coronary artery bypass grafting.

Lymph flow, ionic and biochemical indicators of lymph and blood during hypoxia.

In this study, the biochemical parameters and physico-chemical reactions of the body in experimental hypoxia, using a Sprague Dawley Rat Model. Hypoxia changed the dynamics and biochemical parameters of blood and lymph, as well as urine. During hypoxia, there was a change in the osmotic resistance of erythrocytes. Hypoxic training was conducted in a hypoxic animal chamber for 15 days and 30 days for 40 minutes every day. Physical and chemical parameters of blood, lymph and its morphological composition were studied on a hematological analyser, oxygen tension and pH of blood and lymph on an OPTI CCA-TS2 Blood Gas and Electrolyte Analyser. The value of osmotic pressure in the lymph changed slightly from 280.22 ± 2.07 to 293.3±3.1 and 285.6 ± 2.8 mOsm/l, respectively, 15 and 30 days of hypoxia. Urine osmotic pressure decreased by 15.1-10.4%, respectively, compared to the control group. After 15 and 30 days of hypoxia, ion exchange in the blood plasma showed a decrease in the concentration of K+, Cl- ions and an increase in the concentration of Na+ ions in the blood plasma and lymph. Ca2+ concentrations decreased in blood plasma and increased in lymph and urine. The analysis of the osmotic resistance of erythrocytes showed its decrease. Lipid peroxidation of erythrocyte membranes showed a significant increase in the level of malondialdehyde and diene conjugates by 52.2% and 69.6%, as well as a decrease in the activity of superoxide dismutase and catalase by 32% and 29.7%. Hypoxia leads to a decrease in erythrocyte resistance and lipid peroxidation in experimental animals. Shifts in pH on the side of acidosis and disturbances in physico-chemical properties in the blood and lymph were detected. As a result of developing hypoxia in the body, structural and functional rearrangements occur in the whole blood of experimental animals.

Neurogenic Regulation of Cerebral Blood Flow

The brain has a well-developed vascular network, which allows it to consume up to 15% of the cardiac output with a low mass relative to the whole-body weight. Normally, the metabolic demands of the brain depend considerably on the intensity of functioning of its different departments, which requires constant regulation of the local blood flow level. On the other hand, the state of systemic hemodynamics can have a significant impact on the organ blood flow. Complex and multilevel mechanisms of the regulation of organ cerebral blood flow are aimed at minimizing the possible adverse effects of systemic hemodynamics impairment. The importance of precise and prompt regulation of cerebral blood flow is reinforced by the absence of energy reserves or substrates for its autonomous production in the nervous tissue. The main mechanisms of cerebral blood flow regulation include: myogenic regulation, influence of local humoral influences and vasoactive substances (hormones, metabolites) of systemic blood flow, changes in blood gas composition (increase or decrease in blood oxygen or carbon dioxide tension). In addition, endothelium-dependent mechanisms of regulation are distinguished. Finally, one more level of cerebral arterial tone regulation is represented by the effect of neurotransmitters released from vasomotor fibers terminals of sympathetic and parasympathetic sections of autonomic nervous system, as well as from subcortical neurons and cortical interneurons terminals. In the present review, the principles of neurogenic regulation of cerebral blood flow are considered. The neurogenic regulation of vascular tone is the most complex regulatory circuit. The autonomic innervation of cerebral vessels has significant features that distinguish it from that in most other organs of the great circulatory circle. In addition to the autonomic innervation proper, the vessels of the brain receive sensory innervation, and the small intracerebral arterioles are also innervated -directly by subcortical neurons and cortical interneurons. In this connection, a deeper understanding of the molecular mechanisms of the neurogenic regulation of cerebral blood flow may serve as a basis for the development of new methods of treatment of severe brain diseases based on neuromodulation in the long term.

Clinical effectiveness of phospholipids in patients with restrictive respiratory failure due to lung tissue inflammation

Objective — to analyze the clinical effectiveness use of phosphatidylcholine liposomes in the treatment of patients with restrictive respiratory failure caused by acute pneumonia and pneumonia with a prolonged course. Materials and methods. A prospective cohort study of 68 people was conducted on the basis of the pulmonology department of the Kirovohrad Regional Hospital of the Kirovohrad Regional State in 2020—2021. The people were divided into two groups: I (n = 20) — control group, II (n = 48) — experimental group. They were composed of men aged 25 to 40 years. The first group consisted of healthy individuals who underwent a preventive examination. The second group included patients who, in addition to the traditional treatment of pneumonia, were treated with phospholipids in liposomal form. The drug was used by inhalation according to the instructions. In the course of the experiment, the volume-time indicators of external respiration and gas exchange of the body were studied in dynamics. Results and discussion. The introduction of phospholipids in liposomal form had a positive effect on the restoration of the function of external respiration from the 5th day of treatment of the disease. This is evidenced by the gradual normalization of breathing rate and respiratory volume. It was shown that the ratio of alveolar ventilation and minute respiratory volume was significantly lower and ranged from 60.3 to 72.7 % (with a control value of 72.2 to 77.4 %). Oxygen consumption increased by approximately 76 % on the 5th day of the disease, which indicates a pronounced increase in the level of oxidative metabolism in the body during this pathological process. Recovery could be observed due to optimization of the body’s oxygen supply. Regarding carbon dioxide release, this indicator was almost 2.3 times higher than the control values ​​on the 5th day of the disease. This contributes to the development of metabolic acidosis, which in turn leads to respiratory alkalosis. Against the background of phosphatidylcholine liposomes treatment, this indicator gradually decreased and had a tendency to approach control values ​​a month after treatment (0.216 ± ± 0.042) l/min). Another of the studied indicators is the dead breathing space. According to this indicator, the efficiency of external breathing also increased. The minute volume of blood flow in healthy individuals was (6.5 ± 0.7). During the disease, it decreased to (4.7 ± 0.8) with gradual recovery, starting from the 10th day of treatment with phospholipids. There is also a decrease in the oxygen saturation of the arterial blood and a decrease in the use of oxygen, which can be judged by the characteristics of the venous blood; at the same time, the determined oxygen consumption increases due to hyperventilation. One month after the treatment, these indicators were no longer significantly different from the control values. A similar trend is noted in the analysis of oxygen tension in arterial and venous blood, with a gradual normalization of indicators against the background of the use of phosphatidylcholine liposomes. The determination of the alveolar-arterial difference in oxygen showed an increase in the indicator in the experimental group compared to the control group. Most of the indicators we studied contributed to the decrease in oxygen, thus increasing the efficiency of external respiration. Conclusions. Phosphatidylcholine liposomes are an effective means of complex therapy of pneumonia. The drug has a normalizing effect on the level of energy metabolism in the body and normalizes oxygen consumption, contributing to a faster recovery of the optimal intensity of metabolic processes.

Early changes in cerebral metabolism after perinatal hypoxia-ischemia: a study in normothermic and hypothermic piglets

IntroductionHypoxic ischemic encephalopathy (HIE) after a perinatal insult is a dynamic process that evolves over time. Therapeutic hypothermia (TH) is standard treatment for severe to moderate HIE. There is a lack of evidence on the temporal change and interrelation of the underlying mechanisms that constitute HIE under normal and hypothermic conditions. We aimed to describe early changes in intracerebral metabolism after a hypoxic-ischemic insult in piglets treated with and without TH and in controls.MethodsThree devices were installed into the left hemisphere of 24 piglets: a probe measuring intracranial pressure, a probe measuring blood flow and oxygen tension, and a microdialysis catheter measuring lactate, glucose, glycerol, and pyruvate. After a standardized hypoxic ischemic insult, the piglets were randomized to either TH or normothermia.ResultsGlycerol, a marker of cell lysis, increased immediately after the insult in both groups. There was a secondary increase in glycerol in normothermic piglets but not in piglets treated with TH. Intracerebral pressure, blood flow, oxygen tension, and extracellular lactate remained stable during the secondary increase in glycerol.ConclusionThis exploratory study depicted the development of the pathophysiological mechanisms in the hours following a perinatal hypoxic-ischemic insult with and without TH and controls.

Development of the first vascular-specific KATP channel inhibitor for the treatment of patent ductus arteriosus in newborns

Development of the first vascular-specific KATP channel inhibitor for the treatment of patent ductus arteriosus in newborns

Impact of Tocilizumab and convalescent plasma on lung function in severe COVID-19

Background. Severe COVID-19 occurs in 25—30% of patients. Lung injury is manifested by acute respiratory distress syndrome (ARDS). This event is typical for severe course of disease. The main treatment is immunobiological therapy involving monoclonal antibodies (interleukin-6 receptor blockers) and convalescent plasma. Objective. To evaluate the effect of Tocilizumab and convalescent plasma on gas exchange function of lungs in patients with severe COVID-19. Material and methods. The study included 26 patients. All patients were divided into 2 groups: group I — Tocilizumab alone, group II — Tocilizumab with convalescent plasma. We assessed acid-base status of arterial blood, hospital- and ICU-stay, duration and parameters of respiratory support. Results. Tocilizumab significantly improves oxygenation after 3 days (p=0.01). We found no significant between-group difference in other parameters. Conclusion. Tocilizumab contributes to normalization and significant increment of oxygen tension in arterial blood, oxygen saturation and P/f ratio within three days after the first injection of the drug. Convalescent plasma does not affect gas exchange function of lungs and parameters of respiratory support.

Placental capillary pericytes release excess extracellular vesicles under hypoxic conditions inducing a pro-angiogenic profile in term pregnancy

Pericytes are multifunctional cells wrapped around capillary endothelia, essential for vascular health, development, and blood flow regulation, although their role in human placental chorionic villi has not been fully explored. The second half of normal pregnancy is characterized by a progressive decline in placental and fetal oxygen levels which, by term, comprises a substantial degree of hypoxia. We hypothesized this hypoxia would stimulate pericyte regulation of chorionic villous capillary function. This study's objective was to investigate the role of hypoxia on normal term placental pericytes (PLVP) and their signaling to endothelial cells. First, we confirmed fetoplacental hypoxia at term by a new analysis of umbilical arterial blood oxygen tension of 3,010 healthy singleton neonates sampled at caesarean section and before labor. We then measured the release of cytokines, chemokines, and small extracellular vesicles (PLVPsv), from PLVP cultured at 20%, 8% and 1% O2. As O2 levels decreased, secreted cytokines and chemokines [interleukin-6 (IL-6), interleukin-1α (IL-1α) and vascular endothelial growth factor (VEGF)], and small extracellular vesicle markers, (Alix, Syntenin and CD9) increased significantly in the culture supernatants. When primary human umbilical vein endothelial cells (HUVEC) were cultured with PLVPsv, polygon formation, number, and tube formation length was significantly increased compared to cells not treated with PLVPsv, indicating PLVPsv stimulated angiogenesis. We conclude that adding PLVPsv stimulates angiogenesis and vessel stabilization on neighboring endothelial cells in response to hypoxia in term pregnancy compared to no addition of PLVPsv. Our finding that PLVP can release angiogenic molecules via extracellular vesicles in response to hypoxia may apply to other organ systems.

Oxygen sensing in the ductus arteriosus-A unifying vision for two concepts.

Closure of the ductus arteriosus at birth is known to be related to the physiological rise in blood oxygen tension. Two main schemes have been proposed to explain the peculiar contraction of the ductus to oxygen, and their function is based on distinct sensor-effector complexes. Specifically, these schemes comprise a cytochrome P450 monooxygenase-endothelin complex or, alternatively, a mitochondrial redox mechanism-voltage gated potassium channel complex. However, it is not clear how these systems may relate to the closure process. Here, it is proposed that they operate jointly within a single functional entity, with their combined activation being required for a full-fledged contraction of the vessel to oxygen. This arrangement is thought to ensure a smooth transition from the powerful relaxant mechanism that is evident through the early postnatal period. Validation of this concept would not only settle a central question in the operation of the ductus but may also afford a broader perspective in any future translational research.

Correlation Between Cerebral Tissue Oxygen Saturation and Oxygen Extraction Fraction During Anesthesia: Monitoring Cerebral Metabolic Demand-supply Balance During Vasopressor Administration.

The speculation that cerebral tissue oxygen saturation (SctO 2 ) measured using tissue near-infrared spectroscopy reflects the balance between cerebral metabolic rate of oxygen and cerebral oxygen delivery has not been validated. Our objective was to correlate SctO 2 with cerebral oxygen extraction fraction (OEF) measured using positron emission tomography; OEF is the ratio between cerebral metabolic rate of oxygen and cerebral oxygen delivery and reflects the balance between these 2 variables. This cohort study was based on data collected in a previously published trial assessing phenylephrine versus ephedrine treatment in anesthetized patients undergoing brain tumor surgery. The variables of interest were measured twice over the healthy hemisphere before surgery: the first measurement performed after anesthesia induction and the second measurement performed after induction of a ∼20% increase in blood pressure using either phenylephrine or ephedrine. Data from 24 patients were analyzed. The overall vasopressor-induced relative changes in SctO 2 (ΔSctO 2 ) and OEF (ΔOEF) were 3.16% [interquartile range, -0.73% to 6.04%] and -12.5% [interquartile range, -24.0% to -6.19%], respectively. ΔSctO 2 negatively correlated with ΔOEF after phenylephrine treatment (Spearman rank correlation coefficient [ rs ]=-0.76; P =0.007), ephedrine treatment ( rs =-0.76; P =0.006), and any treatment ( rs =-0.79; P <0.001). ΔSctO 2 significantly associated with ΔOEF based on multivariable analysis with ΔOEF, relative changes in mean arterial pressure, arterial blood oxygen tension, and the bispectral index as covariates ( P =0.036). The negative correlation between changes in SctO 2 and OEF suggests that SctO 2 may reflect the cerebral metabolic demand-supply balance during vasopressor treatment. The generalizability of our findings in other clinical scenarios remains to be determined.

Effects of Local Anesthetics With Vasoconstrictors on Dental Pulp Blood Flow and Oxygen Tension.

The aim of this study was to investigate the changes in pulpal blood flow (PBF) and pulpal oxygen tension (PpulpO2) after injecting local anesthetics with vasoconstrictors. Under general anesthesia, male Japanese White rabbits were injected with 0.6 mL of 2% lidocaine with 1:80,000 epinephrine (LE) or 3% propitocaine (prilocaine) with 0.03 IU felypressin (PF) at the apical area of the lower incisor. Relative to baseline, PBF and PpulpO2 significantly decreased 5 minutes after LE or PF injection as compared with saline. The decrease in PBF was significantly lower in the LE group than in the PF group. Although the LE group had a larger decrease in PpulpO2 relative to baseline than the PF group did, that difference was not significant. PBF and PpulpO2 recovered to baseline faster in the PF group than in the LE group. The injection of local anesthetic solutions containing vasoconstrictors (LE or PF) transiently caused significant decreases in PBF that resulted in significant decreases in PpulpO2. The recovery of PpulpO2 was faster than PBF regardless of the vasoconstrictor used.

Effect of Hyperbaric Oxygenation on Blood Cytokines and Arginine Derivatives; No Evidence for Induction of Inflammation or Endothelial Injury

(1) Background: Hyperbaric oxygen therapy (HBOT) uses 100% oxygen delivered at 1.5–3 times the atmospheric pressure in a specialised chamber to achieve supraphysiological oxygen tension in blood and tissues. Besides its target, HBOT may affect inflammation, endothelial function or angiogenesis. This study analysed the effect of HBOT on blood concentrations of factors that may affect these processes in patients with necrotizing soft-tissue infections (NSTI), aseptic bone necrosis (ABN) and idiopathic sudden sensory neural hearing loss (ISSNHL). (2) Methods: Concentrations asymmetric dimethylarginine (ADMA) and other arginine derivatives were measured with liquid chromatography/mass spectrometry, whereas ELISA was used to quantitate vascular endothelial growth factor (VEGF) and cytokines (IL-1, IL-4, IL-6, IL-10, TGF-β) before and after HBOT in 80 patients (NSTI n = 21, ISSNHL n = 53, ABN n = 6). (3) Results: While some differences were noted between patient groups in ADMA and other arginine derivatives as well as in cytokine concentrations, HBOT did not affect any of these parameters. (4) Conclusions: While cytokines and arginine derivatives concentrations were modified by underlying pathology, hyperbaric oxygenation did not immediately modify it suggesting that it is neutral for inflammation and is not inducing endothelial injury.

Hyperoxia During Cardiopulmonary Bypass Is Associated With Mortality in Infants Undergoing Cardiac Surgery.

Patients undergoing cardiac surgery using cardiopulmonary bypass have variable degrees of blood oxygen tension during surgery. Hyperoxia has been associated with adverse outcomes in critical illness. Data are not available regarding the association of hyperoxia and outcomes in infants undergoing cardiopulmonary bypass. We hypothesize that among infants undergoing cardiac surgery, hyperoxia during cardiopulmonary bypass is associated with greater odds of morbidity and mortality. Retrospective study. Single center at an academic tertiary children's hospital. All infants (< 1 yr) undergoing cardiopulmonary bypass between January 1, 2015, and December 31, 2017, excluding two patients who were initiated on extracorporeal membrane oxygenation in the operating room. None. The study included 469 infants with a median age of 97 days (interquartile range, 14-179 d), weight 4.9 kg (interquartile range, 3.4-6.4 kg), and cardiopulmonary bypass time 128 minutes (interquartile range, 91-185 min). A Pao2 of 313 mm Hg (hyperoxia) on cardiopulmonary bypass had highest sensitivity with specificity greater than 50% for association with operative mortality. Approximately, half of the population (237/469) had hyperoxia on cardiopulmonary bypass. Infants with hyperoxia were more likely to have acute kidney injury, prolonged postoperative length of stay, and mortality. They were younger, weighed less, had longer cardiopulmonary bypass times, and had higher Society of Thoracic Surgeons and the European Association for Cardio-Thoracic Surgery mortality scores. There was no difference in sex, race, preoperative creatinine, single ventricle physiology, or presence of genetic syndrome. On multivariable analysis, hyperoxia was associated with greater odds of mortality (odds ratio, 4.3; 95% CI, 1.4-13.2) but failed to identify an association with acute kidney injury or prolonged postoperative length of stay. Hyperoxia was associated with greater odds of mortality in subgroup analysis of neonatal patients. Hyperoxia occurred in a substantial portion of infants undergoing cardiopulmonary bypass for cardiac surgery. Hyperoxia during cardiopulmonary bypass was an independent risk factor for mortality and may be a modifiable risk factor. Furthermore, hyperoxia during cardiopulmonary bypass was associated with four-fold greater odds of mortality within 30 days of surgery. Hyperoxia failed to identify an association with development of acute kidney injury or prolonged postoperative length of stay when controlling for covariables. Validation of our data among other populations is necessary to better understand and elucidate potential mechanisms underlying the association between excess oxygen delivery during cardiopulmonary bypass and outcome.

A new therapeutic target for patent ductus arteriosus

The ductus arteriosus (DA) maintains the fetal circulation by connecting the aorta and pulmonary arteries. Patent ductus arteriosus (PDA) occurs in >70% extremely-low-birth-weight infants. Patients with PDA exhibit circulatory failure, which is caused by left-to-right shunt. The DA immediately contracts after birth in response to the elevation of blood oxygen tension and to the decline in circulating prostaglandin E2 (PGE2). Cyclooxygenase inhibitors targeting smooth muscle cell (SMC) contraction represent only pharmacological treatment for PDA. However, it is important for DA anatomical closure that intimal thickening (IT) is appropriately formed between SMC layer and endothelial cells (EC). IT begins to form before the second-trimester and becomes prominent toward the end of third-trimester as an increase in placenta-derived PGE2. Immature DAs frequently fail to be close due to poorly formed IT. IT consists of extracellular matrices (ECM) and migrated DA-SMCs from the tunica media. A glycoprotein fibulin-1 is expressed in developing cardiovascular system and binds to multiple ECMs. We found that PGE2 increased fibulin-1 via EP4 in DA-SMCs, and Fbln1-deficient mice exhibited PDA with poor IT formation. Although EP4 is a Gs-coupled GPCR, fibulin-1 was secreted from DA-SMCs through the phospholipase C-protein kinase C-non-canonical NFκB signaling pathway. Fibulin-1 bound to DA-EC-derived versican which is a binding partner of hyaluronan, which promoted directional DA-SMC migration toward ECs and contributed to IT formation in the DA. Fibulin-1 upregulation by the activation of specific downstream pathway of EP4 may serve a new pharmacological strategy for PDA.

Changes in Arterial Blood Pressure and Oxygen Tension as a Result of Hoisting in Isoflurane Anesthetized Healthy Adult Horses.

Background: In anesthetized adult horses, changes in recumbency can influence the cardiovascular system but how arterial blood pressures and oxygen tension change in isoflurane anesthetized animals as a direct result of hoisting has not been investigated.Objective: To evaluate effects of hoisting on hemodynamic function and pulmonary gas exchange in isoflurane-anesthetized horses.Study Design: Prospective, experimental study.Methods: Six adult horses were anesthetized three times using isoflurane in pure oxygen (inspired fraction 0.9–1.0), and allowed breathing spontaneously in lateral recumbency. After 45 min horses were hoisted using a single hoist-hobble system for 5 min and returned into left lateral recumbency. Heart rate (HR), respiratory rate (RR), and systolic (SAP), diastolic (DAP), and mean arterial blood pressures (MAP) were measured every minute starting from 5 min before to 5 min after hoisting. Arterial blood gas samples were collected before, during, and after hoisting.Results: Significant changes in hemodynamic parameters and PaO2 but not PaCO2 were found between baseline recordings and measurements obtained during and early after hoisting. The MAP decreased within the 1st min of hoisting from a mean of 74 ± 17 mmHg at baseline to 57 ± 20 mmHg (p < 0.05). Thereafter, it rapidly recovered to baseline before continuing to rise to higher than baseline values and then remaining elevated for 5 min after horses were returned into lateral recumbency. Simultaneously, the HR increased by 6–9 beats per min during the initial 3 min of hoisting before returning close to baseline values (p < 0.05). The PaO2 decreased significantly from a mean of 324.9 ±137.0 mmHg at baseline to a mean of 141.3 ± 104.2 mmHg during hoisting (p < 0.001) without recovering any more to baseline values.Clinical significance: Hoisting an adult horse during or at the end of isoflurane anesthesia carries the risk of a precipitous, though short-lived (1–2 min), drop in arterial blood pressures and a persistent decrease in arterial oxygenation. While in systemically healthy animals the observed functional impairments were not life-threatening, they may be more severe in systemically compromised horses.Therefore, arterial blood pressures and oxygenation must be carefully monitored when hoisting sick equine patients during or at the end of inhalant anesthesia.

Supplemental CO2 improves oxygen saturation, oxygen tension, and cerebral oxygenation in acutely hypoxic healthy subjects.

Oxygen is viewed in medicine as the sole determinant of tissue oxygenation, though carbon dioxide homeostasis is equally important and clinically often ignored. The aims of this study were as follows: (a) to examine the effects of different acute hypoxic conditions on partial pressure of arterial oxygen (PaO2), arterial oxygen saturation of hemoglobin (SaO2), and regional cerebral saturation of hemoglobin (rSO2); and (b) to evaluate supplemental CO2 as a tool to improve oxygenation in acutely hypoxic individuals. We hypothesized that exposure to gas mixtures with added CO2 would improve oxygenation in hypoxic human subjects. Twenty healthy subjects were exposed to 5‐min intervals of two gas mixtures: hypoxic gas mixture containing 8% oxygen, and a CO2‐enriched mixture containing 8% oxygen plus either 3% or 5% CO2. Ten subjects received the 3% CO2‐enriched mixture, and the remaining 10 subjects received the 5% CO2‐enriched mixture. The order of exposure was randomized. Blood gases, pulse oximetry, end‐tidal CO2, and cerebral oximetry were measured. Compared to the purely hypoxic gas group, PaO2 was increased in the 3% and 5% CO2‐enriched groups by 14.9 and 9.5 mmHg, respectively. Compared to pure hypoxia, SaO2 was increased in the 3% and 5% CO2‐enriched groups by 16.8% and 12.9%, respectively. Both CO2‐enriched gas groups had significantly higher end‐exposure rSO2 and recovered to baseline rSO2 within 1 min, compared to the pure hypoxic gas group, which returned to baseline in 5 min. These results suggest that in acutely hypoxic subjects, CO2 supplementation improves blood oxygen saturation and oxygen tension as well as cerebral oxygenation measures.