Prognostic Factors Associated With Intracranial Hemorrhage and Ischemic Stroke During Venovenous Extracorporeal Membrane Oxygenation: A Systematic Review.

Objectives: Venovenous extracorporeal membrane oxygenation (ECMO) is a life-preserving intervention for patients with respiratory failure refractory to conventional mechanical ventilation. Intracranial hemorrhage (ICH) and ischemic stroke are life-threatening complications associated with venovenous ECMO. Despite this, little is known regarding the prognostic factors associated with these adverse neurologic events.

Neurovascular coupling methods in healthy individuals using transcranial doppler ultrasonography: A systematic review and consensus agreement.

Neurovascular coupling (NVC) is the perturbation of cerebral blood flow (CBF) to meet varying metabolic demands induced by various levels of neural activity. NVC may be assessed by Transcranial Doppler ultrasonography (TCD), using task activation protocols, but with significant methodological heterogeneity between studies, hindering cross-study comparisons. Therefore, this review aimed to summarise and compare available methods for TCD-based healthy NVC assessments.

Evidence for direct CO -mediated alterations in cerebral oxidative metabolism in humans.

Aim: How the cerebral metabolic rates of oxygen and glucose utilization (CMRO and CMR, respectively) are affected by alterations in arterial PCO (PaCO) is equivocal and therefore was the primary question of this study.

Methods: This retrospective analysis involved pooled data from four separate studies, involving 41 healthy adults (35 males/6 females). Participants completed stepwise steady-state alterations in PaCO ranging between 30 and 60 mmHg.

Shining a light on cerebral autoregulation: Are we anywhere near the truth?

The near-infrared spectroscopy (NIRS)-derived cerebral oximetry index (COx) has become popularized for non-invasive neuromonitoring of cerebrovascular function in post-cardiac arrest patients with hypoxic-ischemic brain injury (HIBI). We provide commentary on the physiologic underpinnings and assumptions of NIRS and the COx, potential confounds in the context of HIBI, and the implications for the assessment of cerebral autoregulation.

Impact of Skin Pigmentation on Cerebral Regional Saturation of Oxygen Using Near-Infrared Spectroscopy: A Systematic Review.

Objectives: Near-infrared spectroscopy (NIRS) is used in critical care settings to measure regional cerebral tissue oxygenation (rSo). However, the accuracy of such measurements has been questioned in darker-skinned individuals due to the confounding effects of light absorption by melanin. In this systematic review, we aim to synthesize the available evidence on the effect of skin pigmentation on rSo readings.

Severe hypoxaemic hypercapnia compounds cerebral oxidative-nitrosative stress during extreme apnoea: Implications for cerebral bioenergetic function.

We examined the extent to which apnoea-induced extremes of oxygen demand/carbon dioxide production impact redox regulation of cerebral bioenergetic function. Ten ultra-elite apnoeists (six men and four women) performed two maximal dry apnoeas preceded by normoxic normoventilation, resulting in severe end-apnoea hypoxaemic hypercapnia, and hyperoxic hyperventilation designed to ablate hypoxaemia, resulting in hyperoxaemic hypercapnia. Transcerebral exchange of ascorbate radicals (by electron paramagnetic resonance spectroscopy) and nitric oxide metabolites (by tri-iodide chemiluminescence) were calculated as the product of global cerebral blood flow (by duplex ultrasound) and radial arterial (a) to internal jugular venous (v) concentration gradients.

Characterizing the Relationship Between Arterial Carbon Dioxide Trajectory and Serial Brain Biomarkers with Central Nervous System Injury During Veno-Venous Extracorporeal Membrane Oxygenation: A Prospective Cohort Study.

Background: Central nervous system (CNS) injury following initiation of veno-venous extracorporeal membrane oxygenation (VV-ECMO) is common. An acute decrease in partial pressure of arterial carbon dioxide (PaCO) following VV-ECMO initiation has been suggested as an etiological factor, but the challenges of diagnosing CNS injuries has made discerning a relationship between PaCO and CNS injury difficult.

Methods: We conducted a prospective cohort study of adult patients undergoing VV-ECMO for acute respiratory failure.

Cerebral uptake of microvesicles occurs in normocapnic but not hypocapnic passive hyperthermia in young healthy male adults.

Passive hyperthermia causes cerebral hypoperfusion primarily from heat-induced respiratory alkalosis. However, despite the cerebral hypoperfusion, it is possible that the mild alkalosis might help to attenuate cerebral inflammation. In this study, the cerebral exchange of extracellular vesicles (microvesicles), which are known to elicit pro-inflammatory responses when released in conditions of stress, were examined in hyperthermia with and without respiratory alkalosis.

Cerebral hemodynamics after cardiac arrest: implications for clinical management.

Following resuscitation from cardiac arrest, hypoxic ischemic brain injury (HIBI) ensues, which is the primary determinant of adverse outcome. The pathophysiology of HIBI can be compartmentalized into primary and secondary injury, resulting from cerebral ischemia during cardiac arrest and reperfusion following successful resuscitation, respectively. During the secondary injury phase, increased attention has been directed towards the optimization of cerebral oxygen delivery to prevent additive injury to the brain.

Recent insights into mechanisms of hypoxia-induced vasodilatation in the human brain.

The cerebral vasculature manages oxygen delivery by adjusting arterial blood in-flow in the face of reductions in oxygen availability. Hypoxic cerebral vasodilatation, and the associated hypoxic cerebral blood flow reactivity, involve many vascular, erythrocytic and cerebral tissue mechanisms that mediate elevations in cerebral blood flow via micro- and macrovascular dilatation. This contemporary review focuses on in vivo human work - with reference to seminal preclinical work where necessary - on hypoxic cerebrovascular reactivity, particularly where recent advancements have been made.

Neuroinflammation and the immune system in hypoxic ischaemic brain injury pathophysiology after cardiac arrest.

Hypoxic ischaemic brain injury after resuscitation from cardiac arrest is associated with dismal clinical outcomes. To date, most clinical interventions have been geared towards the restoration of cerebral oxygen delivery after resuscitation; however, outcomes in clinical trials are disappointing. Therefore, alternative disease mechanism(s) are likely to be at play, of which the response of the innate immune system to sterile injured tissue in vivo after reperfusion has garnered significant interest.

The jugular venous-to-arterial difference during rebreathing and end-tidal forcing: Relationship with cerebral perfusion.

We examined two assumptions of the modified rebreathing technique for the assessment of the ventilatory central chemoreflex (CCR) and cerebrovascular CO reactivity (CVR), hypothesizing: (1) that rebreathing abolishes the gradient between the partial pressures of arterial and brain tissue CO [measured via the surrogate jugular venous and arterial difference (P CO )] and (2) rebreathing eliminates the capacity of CVR to influence the P CO difference, and thus affect CCR sensitivity. We also evaluated these variables during two separate dynamic end-tidal forcing (ETF) protocols (termed: ETF-1 and ETF-2), another method of assessing CCR sensitivity and CVR. Healthy participants were included in the rebreathing (n = 9), ETF-1 (n = 11) and ETF-2 (n = 10) protocols and underwent radial artery and internal jugular vein (advanced to jugular bulb) catheterization to collect blood samples.

Clinical targeting of the cerebral oxygen cascade to improve brain oxygenation in patients with hypoxic-ischaemic brain injury after cardiac arrest.

The cerebral oxygen cascade includes three key stages: (a) convective oxygen delivery representing the bulk flow of oxygen to the cerebral vascular bed; (b) diffusion of oxygen from the blood into brain tissue; and (c) cellular utilisation of oxygen for aerobic metabolism. All three stages may become dysfunctional after resuscitation from cardiac arrest and contribute to hypoxic-ischaemic brain injury (HIBI). Improving convective cerebral oxygen delivery by optimising cerebral blood flow has been widely investigated as a strategy to mitigate HIBI.

Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent and -nitrosothiol mediated signal transduction.

Cerebral hypoxic vasodilation is poorly understood in humans, which undermines the development of therapeutics to optimize cerebral oxygen delivery. Across four investigations (total n = 195) we investigated the role of nitric oxide (NO) and hemoglobin-based -nitrosothiol (RSNO) and nitrite () signaling in the regulation of cerebral hypoxic vasodilation. We conducted hemodilution (n = 10) and NO synthase inhibition experiments (n = 11) as well as hemoglobin oxygen desaturation protocols, wherein we measured cerebral blood flow (CBF), intra-arterial blood pressure, and in subsets of participants trans-cerebral release/uptake of RSNO and .

Manipulation of iron status on cerebral blood flow at high altitude in lowlanders and adapted highlanders.

Cerebral blood flow (CBF) increases during hypoxia to counteract the reduction in arterial oxygen content. The onset of tissue hypoxemia coincides with the stabilization of hypoxia-inducible factor (HIF) and transcription of downstream HIF-mediated processes. It has yet to be determined, whether HIF down- or upregulation can modulate hypoxic vasodilation of the cerebral vasculature.

Prognostic peripheral blood biomarkers at ICU admission predict COVID-19 clinical outcomes.

The COVID-19 pandemic continues to challenge the capacities of hospital ICUs which currently lack the ability to identify prospectively those patients who may require extended management. In this study of 90 ICU COVID-19 patients, we evaluated serum levels of four cytokines (IL-1β, IL-6, IL-10 and TNFα) as well as standard clinical and laboratory measurements. On 42 of these patients (binned into Initial and Replication Cohorts), we further performed CyTOF-based deep immunophenotyping of peripheral blood mononuclear cells with a panel of 38 antibodies.

Cerebral O and CO transport in isovolumic haemodilution: Compensation of cerebral delivery of O and maintenance of cerebrovascular reactivity to CO.

This study investigated the influence of acute reductions in arterial O content (CaO) via isovolumic haemodilution on global cerebral blood flow (gCBF) and cerebrovascular CO reactivity (CVR) in 11 healthy males (age; 28 ± 7 years: body mass index; 23 ± 2 kg/m). Radial artery and internal jugular vein catheters provided measurement of blood pressure and gases, quantification of cerebral metabolism, cerebral CO washout, and trans-cerebral nitrite exchange (ozone based chemiluminescence). Prior to and following haemodilution, the partial pressure of arterial CO (PaCO) was elevated with dynamic end-tidal forcing while gCBF was measured with duplex ultrasound.

A cross-species validation of single-beat metrics of cardiac contractility.

The assessment of left ventricular (LV) contractility in animal models is useful in various experimental paradigms, yet obtaining such measures is inherently challenging and surgically invasive. In a cross-species study using small and large animals, we comprehensively tested the agreement and validity of multiple single-beat surrogate metrics of LV contractility against the field-standard metrics derived from inferior vena cava occlusion (IVCO). Fifty-six rats, 27 minipigs and 11 conscious dogs underwent LV and arterial catheterization and were assessed for a range of single-beat metrics of LV contractility.

Brachial artery responses to acute hypercapnia: The roles of shear stress and adrenergic tone.

New Findings: What is the central question of this study? What are the contributions of shear stress and adrenergic tone to brachial artery vasodilatation during hypercapnia? What is the main finding and its importance? In healthy young adults, shear-mediated vasodilatation does not occur in the brachial artery during hypercapnia, as elevated α₁-adrenergic activity typically maintains vascular tone and offsets distal vasodilatation controlling flow.

Abstract: We aimed to assess the shear stress dependency of brachial artery (BA) responses to hypercapnia, and the α₁-adrenergic restraint of these responses. We hypothesized that elevated shear stress during hypercapnia would cause BA vasodilatation, but where shear stress was prohibited (via arterial compression), the BA would not vasodilate (study 1); and, in the absence of α₁-adrenergic activity, blood flow, shear stress and BA vasodilatation would increase (study 2).

Neurologic Prognostication After Cardiac Arrest Using Brain Biomarkers: A Systematic Review and Meta-analysis.

Importance: Brain injury biomarkers released into circulation from the injured neurovascular unit are important prognostic tools in patients with cardiac arrest who develop hypoxic ischemic brain injury (HIBI) after return of spontaneous circulation (ROSC).

Objective: To assess the neuroprognostic utility of bloodborne brain injury biomarkers in patients with cardiac arrest with HIBI.

Data Sources: Studies in electronic databases from inception to September 15, 2021.

Hypoxemia increases blood-brain barrier permeability during extreme apnea in humans.

Voluntary asphyxia imposed by static apnea challenges blood-brain barrier (BBB) integrity in humans through transient extremes of hypertension, hypoxemia and hypercapnia. In the present study, ten ultra-elite breath-hold divers performed two maximal dry apneas preceded by normoxic normoventilation (NX: severe hypoxemia and hypercapnia) and hyperoxic hyperventilation (HX: absence of hypoxemia with exacerbating hypercapnia) with measurements obtained before and immediately after apnea. Transcerebral exchange of NVU proteins (ELISA, Single Molecule Array) were calculated as the product of global cerebral blood flow (gCBF, duplex ultrasound) and radial arterial to internal jugular venous concentration gradients.

Persistently elevated complement alternative pathway biomarkers in COVID-19 correlate with hypoxemia and predict in-hospital mortality.

Mechanisms underlying the SARS-CoV-2-triggered hyperacute thrombo-inflammatory response that causes multi-organ damage in coronavirus disease 2019 (COVID-19) are poorly understood. Several lines of evidence implicate overactivation of complement. To delineate the involvement of complement in COVID-19, we prospectively studied 25 ICU-hospitalized patients for up to 21 days.