Identifying Frailty Using Point-of-Care Ultrasonography: Image Acquisition and Assessment.

Frailty is a significant predictor of a range of adverse outcomes in surgical patients, including increased mechanical ventilation time, longer hospital stays, unplanned readmissions, stroke, delirium, and death. However, accessible tools for screening in clinical settings are limited. Computed tomography of the psoas muscle is the current standard imaging device for measuring frailty, but it is expensive, time-consuming, and exposes the patient to ionizing radiation.

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.

Selected and shared hematological responses to apnea in elite human free divers and northern elephant seals ().

Despite elite human free divers achieving incredible feats in competitive free diving, there has yet to be a study that compares consummate divers, (i.e. northern elephant seals) to highly conditioned free divers (i.

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.

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.

Intense exercise at high altitude causes platelet loss across the brain in humans.

Platelets are known primarily for their role in blood clotting; however, it is becoming clear that they play diverse roles beyond that of haemostasis. Exercise has been shown to activate platelets and stimulate neurogenesis, neuroplasticity and improve cognitive function, highlighting a potentially powerful link between platelet function and brain health. Despite this clear link between platelets and the brain, very little is known about the behaviour of platelets through the cerebral circulation in humans.

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 .

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.

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.

Trans-cerebral HCO and PCO exchange during acute respiratory acidosis and exercise-induced metabolic acidosis in humans.

This study investigated trans-cerebral internal jugular venous-arterial bicarbonate ([HCO]) and carbon dioxide tension (PCO) exchange utilizing two separate interventions to induce acidosis: 1) acute respiratory acidosis via elevations in arterial PCO (PaCO) (n = 39); and 2) metabolic acidosis via incremental cycling exercise to exhaustion (n = 24). During respiratory acidosis, arterial [HCO] by 0.15 ± 0.

Nitric oxide contributes to cerebrovascular shear-mediated dilatation but not steady-state cerebrovascular reactivity to carbon dioxide.

Cerebrovascular CO reactivity (CVR) is often considered a bioassay of cerebrovascular endothelial function. We recently introduced a test of cerebral shear-mediated dilatation (cSMD) that may better reflect endothelial function. We aimed to determine the nitric oxide (NO)-dependency of CVR and cSMD.

GLOBAL REACH 2018: intra-arterial vitamin C improves endothelial-dependent vasodilatory function in humans at high altitude.

High altitude-induced hypoxaemia is often associated with peripheral vascular dysfunction. However, the basic mechanism(s) underlying high-altitude vascular impairments remains unclear. This study tested the hypothesis that oxidative stress contributes to the impairments in endothelial function during early acclimatization to high altitude.

Prolonged progressive hypermetabolism during COVID-19 hospitalization undetected by common predictive energy equations.

Background & Aims: Indirect calorimetry (IC) is the gold-standard for determining measured resting energy expenditure (mREE) in critical illness. When IC is not available, predicted resting energy expenditure (pREE) equations are commonly utilized, which often inaccurately predict metabolic demands leading to over- or under-feeding. This study aims to longitudinally assess mREE via IC in critically ill patients with SARS-CoV-2 (COVID-19) infection throughout the entirety of, often prolonged, intensive care unit (ICU) stays and compare mREE to commonly utilized pREE equations.

The influence of hemoconcentration on hypoxic pulmonary vasoconstriction in acute, prolonged, and lifelong hypoxemia.

Hemoconcentration can influence hypoxic pulmonary vasoconstriction (HPV) via increased frictional force and vasoactive signaling from erythrocytes, but whether the balance of these mechanism is modified by the duration of hypoxia remains to be determined. We performed three sequential studies: ) at sea level, in normoxia and isocapnic hypoxia with and without isovolumic hemodilution ( = 10, aged 29 ± 7 yr); ) at altitude (6 ± 2 days acclimatization at 5,050 m), before and during hypervolumic hemodilution ( = 11, aged 27 ± 5 yr) with room air and additional hypoxia [fraction of inspired oxygen ([Formula: see text])= 0.15]; and ) at altitude (4,340 m) in Andean high-altitude natives with excessive erythrocytosis (EE; = 6, aged 39 ± 17 yr), before and during isovolumic hemodilution with room air and hyperoxia (end-tidal Po = 100 mmHg).

Regulation of cerebral blood flow by arterial PCO independent of metabolic acidosis at 5050 m.

Key Points: We investigated the influence of arterial PCO (PaCO ) with and without experimentally altered pH on cerebral blood flow (CBF) regulation at sea level and with acclimatization to 5050 m. At sea level and high altitude, we assessed stepwise alterations in PaCO following metabolic acidosis (via 2 days of oral acetazolamide; ACZ) with and without acute restoration of pH (via intravenous sodium bicarbonate; ACZ+HCO ). Total resting CBF was unchanged between trials at each altitude even though arterial pH and [HCO ] (i.

Influence of iron manipulation on hypoxic pulmonary vasoconstriction and pulmonary reactivity during ascent and acclimatization to 5050 m.

Key Points: Iron acts as a cofactor in the stabilization of the hypoxic-inducible factor family, and plays an influential role in the modulation of hypoxic pulmonary vasoconstriction. It is uncertain whether iron regulation is altered in lowlanders during either (1) ascent to high altitude, or (2) following partial acclimatization, when compared to high-altitude adapted Sherpa. During ascent to 5050 m, the rise in pulmonary artery systolic pressure (PASP) was blunted in Sherpa, compared to lowlanders; however, upon arrival to 5050 m, PASP levels were comparable in both groups, but the reduction in iron bioavailability was more prevalent in lowlanders compared to Sherpa.

Nitric oxide is fundamental to neurovascular coupling in humans.

Key Points: Preclinical models have demonstrated that nitric oxide is a key component of neurovascular coupling; this has yet to be translated to humans. We conducted two separate protocols utilizing intravenous infusion of a nitric oxide synthase inhibitor and isovolumic haemodilution to assess the influence of nitric oxide on neurovascular coupling in humans. Isovolumic haemodilution did not alter neurovascular coupling.

A methodology to explore ventilatory chemosensitivity and opioid-induced respiratory depression risk.

Reported incidence of postoperative opioid-induced respiratory depression (OIRD) ranges from 0.5-41% and is not reliably predicted by traditional risk factors. This study tests a new methodology to investigate ventilatory chemosensitivity as a new potential risk factor and explore OIRD distribution across sleep and wakefulness.

Assessment of a Non Invasive Brain Oximeter in Volunteers Undergoing Acute Hypoxia.

Introduction: Research in traumatic brain injury suggests better patient outcomes when invasive oxygen monitoring is used to detect and correct episodes of brain hypoxia. Invasive brain oxygen monitoring is, however, not routinely used due to the risks, costs and technical challengers. We are developing a non-invasive brain oximeter to address these limitations.

Acute reductions in haematocrit increase flow-mediated dilatation independent of resting nitric oxide bioavailability in humans.

Changes in haematocrit influence nitric oxide signalling through alterations in shear stress stimuli and haemoglobin scavenging of nitric oxide; these two regulatory factors have not been assessed simultaneously Isovolumic haemodilution led to a marked increase in brachial artery flow-mediated dilatation in humans The increase in flow-mediated dilatation occurred in the face of an unaltered shear stress stimulus for vasodilatation and reduced resting steady-state nitric oxide levels in the blood Collectively, our data point towards haemoglobin scavenging of nitric oxide as a key regulatory factor of brachial flow-mediated dilatation and highlight the importance of the simultaneous consideration of nitric oxide production and inactivation when investigating vascular function in humans ABSTRACT: Haemoglobin (Hb) may impact the transduction of endothelium-dependent and nitric oxide (NO)-mediated vasodilator activity, given its contribution to shear stress stimuli and diverse biochemical reactions with NO. We hypothesized that an acute reduction in [Hb] and haematocrit (Hct) would increase brachial artery flow-mediated dilatation (FMD). In 11 healthy males (28 ± 7 years; 23 ± 2 kg m ), FMD (Duplex ultrasound), arterial blood gases, Hct and [Hb], blood viscosity, and NO metabolites (ozone-based chemiluminescence) were measured before and after isovolumic haemodilution, where ∼20% of whole blood was removed and replaced with 5% human serum albumin.

Implications for Neuromodulation Therapy to Control Inflammation and Related Organ Dysfunction in COVID-19.

COVID-19 is a syndrome that includes more than just isolated respiratory disease, as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) also interacts with the cardiovascular, nervous, renal, and immune system at multiple levels, increasing morbidity in patients with underlying cardiometabolic conditions and inducing myocardial injury or dysfunction. Emerging evidence suggests that patients with the highest rate of morbidity and mortality following SARS-CoV2 infection have also developed a hyperinflammatory syndrome (also termed cytokine release syndrome). We lay out the potential contribution of a dysfunction in autonomic tone to the cytokine release syndrome and related multiorgan damage in COVID-19.

Validation of a Noninvasive Assessment of Pulmonary Gas Exchange During Exercise in Hypoxia.

Background: Pulmonary gas exchange efficiency, determined by the alveolar-to-arterial Po difference (A-aDo), progressively worsens during exercise at sea-level; this response is further elevated during exercise in hypoxia. Traditionally, pulmonary gas exchange efficiency is assessed through measurements of ventilation and end-tidal gases paired with direct arterial blood gas (ABG) sampling. Because these measures have a number of caveats, particularly invasive blood sampling, the development of new approaches for the noninvasive assessment of pulmonary gas exchange is needed.