Effects of Acute Subdural Hematoma-Induced Brain Injury On Energy Metabolism in Peripheral Blood Mononuclear Cells

Zink, Fabian; Vogt, J.; Wachter, Ulrich; Hartert, Jens; Horchler, Mirco; Zhang, Xiaomin; Hezel, Felix; Kapapa, Thomas; Datzmann, Thomas; Hoffmann, Andrea; Wepler, Martin; Calzia, Enrico; Radermacher, Peter; Hartmann, Clair

doi:10.1097/shk.0000000000001642

Cited by 7 publications

(11 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Immediately after sampling arterial whole blood samples were analyzed for superoxide anion (O 2 ⋅ – ) concentrations by electron spin resonance (ESR) as described previously ( 23 ). Briefly, whole blood freshly drawn was mixed with the O 2 ⋅ – -specific spin probe 1-Hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and the metal chelators deferoxamine-methanesulfonate and diethyldithiocarbamic-acid in Krebs-Hepes-Buffer (all chemicals from Noxygen).…”

Section: Methodsmentioning

confidence: 99%

“…At the end of the experiment, immediate post mortem brain tissue specimens from regions adjacent to the brain area next to the ASDH ipsilateral and corresponding contralateral area were analyzed for mitochondrial respiratory activity using “high-resolution respirometry” (Oxygraph-2K ® , Oroboros Instruments) as described previously ( 10 , 23 ). After supplementation of substrates for complexes I, II and ADP, the oxidative phosphorylation (coupled state, OXPHOS) was assessed.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The effect of targeted hyperoxemia in a randomized controlled trial employing a long-term resuscitated, model of combined acute subdural hematoma and hemorrhagic shock in swine with coronary artery disease: An exploratory, hypothesis-generating study

Datzmann

Messerer²,

Münz³

et al. 2022

Front. Med.

Self Cite

View full text Add to dashboard Cite

Controversial evidence is available regarding suitable targets for the arterial O2 tension (PaO2) after traumatic brain injury and/or hemorrhagic shock (HS). We previously demonstrated that hyperoxia during resuscitation from hemorrhagic shock attenuated cardiac injury and renal dysfunction in swine with coronary artery disease. Therefore, this study investigated the impact of targeted hyperoxemia in a long-term, resuscitated model of combined acute subdural hematoma (ASDH)-induced brain injury and HS. The prospective randomized, controlled, resuscitated animal investigation consisted of 15 adult pigs. Combined ASDH plus HS was induced by injection of 0.1 ml/kg autologous blood into the subdural space followed by controlled passive removal of blood. Two hours later, resuscitation was initiated comprising re-transfusion of shed blood, fluids, continuous i.v. noradrenaline, and either hyperoxemia (target PaO2 200 – 250 mmHg) or normoxemia (target PaO2 80 – 120 mmHg) during the first 24 h of the total of 54 h of intensive care. Systemic hemodynamics, intracranial and cerebral perfusion pressures, parameters of brain microdialysis and blood biomarkers of brain injury did not significantly differ between the two groups. According to the experimental protocol, PaO2 was significantly higher in the hyperoxemia group at the end of the intervention period, i.e., at 24 h of resuscitation, which coincided with a higher brain tissue PO2. The latter persisted until the end of observation period. While neurological function as assessed using the veterinary Modified Glasgow Coma Score progressively deteriorated in the control group, it remained unaffected in the hyperoxemia animals, however, without significant intergroup difference. Survival times did not significantly differ in the hyperoxemia and control groups either. Despite being associated with higher brain tissue PO2 levels, which were sustained beyond the intervention period, targeted hyperoxemia exerted neither significantly beneficial nor deleterious effects after combined ASDH and HS in swine with pre-existing coronary artery disease. The unavailability of a power calculation and, thus, the limited number of animals included, are the limitations of the study.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The effect of targeted hyperoxemia in a randomized controlled trial employing a long-term resuscitated, model of combined acute subdural hematoma and hemorrhagic shock in swine with coronary artery disease: An exploratory, hypothesis-generating study

Datzmann

Messerer²,

Münz³

et al. 2022

Front. Med.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Superoxide anion radical concentrations (O 2 •− ) in arterial blood were measured as previously described (23,38). Briefly, blood and the O 2…”

Section: Measurementsmentioning

confidence: 99%

An exploratory study investigating the effect of targeted hyperoxemia in a randomized controlled trial in a long-term resuscitated model of combined acute subdural hematoma and hemorrhagic shock in cardiovascular healthy pigs

et al. 2023

Self Cite

View full text Add to dashboard Cite

Severe physical injuries and associated traumatic brain injury and/or hemorrhagic shock (HS) remain leading causes of death worldwide, aggravated by accompanying extensive inflammation. Retrospective clinical data indicated an association between mild hyperoxemia and improved survival and outcome. However, corresponding prospective clinical data, including long-term resuscutation, are scarce. Therefore, the present study explored the effect of mild hyperoxemia for 24 hours in a prospective randomized controlled trial in a long-term resuscitated model of combined acute subdural hematoma (ASDH) and HS. ASDH was induced by injecting 0.1 ml × kg−1 autologous blood into the subdural space and HS was triggered by passive removal of blood. After 2 hours, the animals received full resuscitation, including retransfusion of the shed blood and vasopressor support. During the first 24 hours, the animals underwent targeted hyperoxemia (PaO2 = 200 – 250 mmHg) or normoxemia (PaO2 = 80 – 120 mmHg) with a total observation period of 55 hours after the initiation of ASDH and HS. Survival, cardiocirculatory stability, and demand for vasopressor support were comparable between both groups. Likewise, humoral markers of brain injury and systemic inflammation were similar. Multimodal brain monitoring, including microdialysis and partial pressure of O2 in brain tissue, did not show significant differences either, despite a significantly better outcome regarding the modified Glasgow Coma Scale 24 hours after shock that favors hyperoxemia. In summary, the present study reports no deleterious and few beneficial effects of mild targeted hyperoxemia in a clinically relevant model of ASDH and HS with long-term resuscitation in otherwise healthy pigs. Further beneficial effects on neurological function were probably missed due to the high mortality in both experimental groups. The present study remains exploratory due to the unavailability of an a priori power calculation resulting from the lack of necessary data.

show abstract

“…We therefore propose our sampling-based model as a suitable method for estimating fluxes within the metabolic network. A preliminary version of this model has already been applied to study the effects of glucocorticoids on macrophage metabolism (43) and, in a more rudimentary form, to investigate the effect of acute subdural hematoma-induced brain injury on peripheral blood mononuclear cell (PBMC) metabolism (44).…”

Section: Introductionmentioning

confidence: 99%

The effect of sodium thiosulfate on immune cell metabolism during porcine hemorrhage and resuscitation

Wolfschmitt

Hogg²,

Vogt³

et al. 2023

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

IntroductionSodium thiosulfate (Na2S2O3), an H2S releasing agent, was shown to be organ-protective in experimental hemorrhage. Systemic inflammation activates immune cells, which in turn show cell type-specific metabolic plasticity with modifications of mitochondrial respiratory activity. Since H2S can dose-dependently stimulate or inhibit mitochondrial respiration, we investigated the effect of Na2S2O3 on immune cell metabolism in a blinded, randomized, controlled, long-term, porcine model of hemorrhage and resuscitation. For this purpose, we developed a Bayesian sampling-based model for 13C isotope metabolic flux analysis (MFA) utilizing 1,2-13C2-labeled glucose, 13C6-labeled glucose, and 13C5-labeled glutamine tracers.MethodsAfter 3 h of hemorrhage, anesthetized and surgically instrumented swine underwent resuscitation up to a maximum of 68 h. At 2 h of shock, animals randomly received vehicle or Na2S2O3 (25 mg/kg/h for 2 h, thereafter 100 mg/kg/h until 24 h after shock). At three time points (prior to shock, 24 h post shock and 64 h post shock) peripheral blood mononuclear cells (PBMCs) and granulocytes were isolated from whole blood, and cells were investigated regarding mitochondrial oxygen consumption (high resolution respirometry), reactive oxygen species production (electron spin resonance) and fluxes within the metabolic network (stable isotope-based MFA).ResultsPBMCs showed significantly higher mitochondrial O2 uptake and lower O2•− production in comparison to granulocytes. We found that in response to Na2S2O3 administration, PBMCs but not granulocytes had an increased mitochondrial oxygen consumption combined with a transient reduction of the citrate synthase flux and an increase of acetyl-CoA channeled into other compartments, e.g., for lipid biogenesis.ConclusionIn a porcine model of hemorrhage and resuscitation, Na2S2O3 administration led to increased mitochondrial oxygen consumption combined with stimulation of lipid biogenesis in PBMCs. In contrast, granulocytes remained unaffected. Granulocytes, on the other hand, remained unaffected. O2•− concentration in whole blood remained constant during shock and resuscitation, indicating a sufficient anti-oxidative capacity. Overall, our MFA model seems to be is a promising approach for investigating immunometabolism; especially when combined with complementary methods.

show abstract

Effects of Acute Subdural Hematoma-Induced Brain Injury On Energy Metabolism in Peripheral Blood Mononuclear Cells

Cited by 7 publications

References 50 publications

The effect of targeted hyperoxemia in a randomized controlled trial employing a long-term resuscitated, model of combined acute subdural hematoma and hemorrhagic shock in swine with coronary artery disease: An exploratory, hypothesis-generating study

The effect of targeted hyperoxemia in a randomized controlled trial employing a long-term resuscitated, model of combined acute subdural hematoma and hemorrhagic shock in swine with coronary artery disease: An exploratory, hypothesis-generating study

An exploratory study investigating the effect of targeted hyperoxemia in a randomized controlled trial in a long-term resuscitated model of combined acute subdural hematoma and hemorrhagic shock in cardiovascular healthy pigs

The effect of sodium thiosulfate on immune cell metabolism during porcine hemorrhage and resuscitation

Contact Info

Product

Resources

About