Transfer function analysis of dynamic cerebral autoregulation: A CARNet white paper 2022 update.

Cerebral autoregulation (CA) refers to the control of cerebral tissue blood flow (CBF) in response to changes in perfusion pressure. Due to the challenges of measuring intracranial pressure, CA is often described as the relationship between mean arterial pressure (MAP) and CBF. Dynamic CA (dCA) can be assessed using multiple techniques, with transfer function analysis (TFA) being the most common. A 2016 white paper by members of an international Cerebrovascular Research Network (CARNet) that is focused on CA strove to improve TFA standardization by way of introducing data acquisition, analysis, and reporting guidelines. Since then, additional evidence has allowed for the improvement and refinement of the original recommendations, as well as for the inclusion of new guidelines to reflect recent advances in the field. This second edition of the white paper contains more robust, evidence-based recommendations, which have been expanded to address current streams of inquiry, including optimizing MAP variability, acquiring CBF estimates from alternative methods, estimating alternative dCA metrics, and incorporating dCA quantification into clinical trials. Implementation of these new and revised recommendations is important to improve the reliability and reproducibility of dCA studies, and to facilitate inter-institutional collaboration and the comparison of results between studies.

Hypoxia is not the primary mechanism contributing to exercise-induced proteinuria.

INTRODUCTION: Proteinuria increases at altitude and with exercise, potentially as a result of hypoxia. Using urinary alpha-1 acid glycoprotein (α1-AGP) levels as a sensitive marker of proteinuria, we examined the impact of relative hypoxia due to high altitude and blood pressure-lowering medication on post-exercise proteinuria. METHODS: Twenty individuals were pair-matched for sex, age and ACE genotype. They completed maximal exercise tests once at sea level and twice at altitude (5035 m). Losartan (100 mg/day; angiotensin-receptor blocker) and placebo were randomly assigned within each pair 21 days before ascent. The first altitude exercise test was completed within 24-48 hours of arrival (each pair within ~1 hour). Acetazolamide (125 mg two times per day) was administrated immediately after this test for 48 hours until the second altitude exercise test. RESULTS: With placebo, post-exercise α1-AGP levels were similar at sea level and altitude. Odds ratio (OR) for increased resting α1-AGP at altitude versus sea level was greater without losartan (2.16 times greater). At altitude, OR for reduced post-exercise α1-AGP (58% lower) was higher with losartan than placebo (2.25 times greater, p=0.059) despite similar pulse oximetry (SpO2) (p=0.95) between groups. Acetazolamide reduced post-exercise proteinuria by approximately threefold (9.3±9.7 vs 3.6±6.0 µg/min; p=0.025) although changes were not correlated (r=-0.10) with significant improvements in SpO2 (69.1%±4.5% vs 75.8%±3.8%; p=0.001). DISCUSSION: Profound systemic hypoxia imposed by altitude does not result in greater post-exercise proteinuria than sea level. Losartan and acetazolamide may attenuate post-exercise proteinuria, however further research is warranted.

Neurovascular coupling and cerebral autoregulation in atrial fibrillation.

The risk of cognitive decline and stroke is increased by atrial fibrillation (AF). We sought to determine whether neurovascular coupling and cerebral autoregulation are blunted in people with AF in comparison with age-matched, patients with hypertension and healthy controls. Neurovascular coupling was assessed using five cycles of visual stimulation for 30 s followed by 30 s with both eyes-closed. Cerebral autoregulation was examined using a sit-stand test, and a repeated squat-to-stand (0.1 Hz) manoeuvre with transfer function analysis of mean arterial pressure (MAP; input) and middle cerebral artery mean blood flow velocity (MCA Vm; output) relationships at 0.1 Hz. Visual stimulation increased posterior cerebral artery conductance, but the magnitude of the response was blunted in patients with AF (18 [8] %; mean [SD]) and hypertension (17 [8] %), in comparison with healthy controls (26 [9] %) (P < 0.05). In contrast, transmission of MAP to MCA Vm was greater in AF patients compared to hypertension and healthy controls, indicating diminished cerebral autoregulation. We have shown for the first time that AF patients have impaired neurovascular coupling responses to visual stimulation and diminished cerebral autoregulation. Such deficits in cerebrovascular regulation may contribute to the increased risk of cerebral dysfunction in people with AF.

Physiological responses to a five-day adventure race: Continuous blood glucose, hemodynamics and metabolites the 2012 GODZone field-study.

BACKGROUND/OBJECTIVE: Adventure racing is an ultra-endurance activity that imposes a unique multifaceted stress on the human body. The purpose of this field study was to examine the physiological responses to a 5-day adventure race. METHODS: Eight competitors, two teams (1 female each) in the 2012 GODZone adventure race volunteered. Competitors trekked, cycled and paddled ∼326 km in ∼116 hours. Continuous glucose was measured the day before and throughout. Body mass, urinary solutes, and blood pressure and heart rate during resting, standing, and repeated squat-stand conditions, were assessed pre and post. RESULTS: Despite no changes in mean blood glucose levels, there was increased glycemic variability (Standard deviation glucose; Pre: 0.5 ±â€¯0.1 vs Race: 1.0 ±â€¯0.2 mmol/L, p = 0.02) and periods of hypoglycemia (i.e., Min glucose Pre: 4.1 ±â€¯0.3 vs Race: 3.6 ±â€¯0.5 mmol/L, p = 0.05) during the race. After the race, the blood pressure during resting, standing and squat-stand conditions was significantly lower, by 14 ±â€¯14 mmHg, 16 ±â€¯15 mmHg and 18 ±â€¯15 mmHg (all p < 0.05), respectively, with no change in heart rate. During five-days of adventure racing there is increased glycemic variability and more frequent periods of low blood glucose levels. Additionally, following the race pronounced hypotension is observed in competitors. CONCLUSION: We observed more frequent glucose fluctuations, lower glucose levels and significant perturbations in blood pressure control. Further research is warranted to examine the long-term impact of adventure racing on metabolic and cardiovascular function.