The effect of CO2 on the age dependence of neurovascular coupling.

Prior studies have identified variable effects of healthy aging on neurovascular coupling (NVC). Carbon dioxide (CO2) affects both cerebral blood velocity (CBv) and NVC, but the effects of age on NVC under different CO2 conditions are unknown. Therefore, we investigated the effects of aging on NVC in different CO2 states in healthy controls during cognitive paradigms. 78 healthy participants (18-78 years) underwent continuous recordings of CBv by bilateral insonation of middle (MCA) and posterior (PCA) cerebral arteries (transcranial Doppler), blood pressure, end-tidal CO2, and heart rate during poikilocapnia, hypercapnia (5% CO2 inhalation) and hypocapnia (paced hyperventilation). Neuroactivation via visuospatial (VS) and attention tasks (AT) augmented CBv. Peak percentage change in MCAv/PCAv, were compared between CO2 conditions and age groups (< 30, 31-60, and >60 years). For the VS task, in normocapnia, younger adults had a lower NVC response compared to older adults (mean difference (MD): -7.92% (standard deviation (SD): 2.37), p=0.004), but comparable between younger and middle-aged groups. In hypercapnia, both younger (MD: -4.75% (SD: 1.56), p=0.009) and middle (MD: -4.58% (SD: 1.69), p=0.023) age groups had lower NVC responses compared to older adults. Finally, in hypocapnia, both older (MD: 5.92% (SD: 2.21), p=0.025) and middle (MD: 5.44% (SD: 2.27), p=0.049) age groups had greater NVC responses, compared to younger adults. In conclusion, the middle-aged adults demonstrated a variable NVC response, comparable to younger adults under hypercapnia, and older adults under hypocapnia. This may owe to a more cognitively favourable profile while under hypercapnic conditions, compared to hypocapnia.

The role of the autonomic nervous system in cerebral blood flow regulation in stroke: A review.

Stroke is a pathophysiological condition which results in alterations in cerebral blood flow (CBF). The mechanism by which the brain maintains adequate CBF in presence of fluctuating cerebral perfusion pressure (CPP) is known as cerebral autoregulation (CA). Disturbances in CA may be influenced by a number of physiological pathways including the autonomic nervous system (ANS). The cerebrovascular system is innervated by adrenergic and cholinergic nerve fibers. The role of the ANS in regulating CBF is widely disputed owing to several factors including the complexity of the ANS and cerebrovascular interactions, limitations to measurements, variation in methods to assess the ANS in relation to CBF as well as experimental approaches that can or cannot provide insight into the sympathetic control of CBF. CA is known to be impaired in stroke however the number of studies investigating the mechanisms by which this occurs are limited. This literature review will focus on highlighting the assessment of the ANS and CBF via indices derived from the analyses of heart rate variability (HRV), and baroreflex sensitivity (BRS), and providing a summary of both clinical and animal model studies investigating the role of the ANS in influencing CA in stroke. Understanding the mechanisms by which the ANS influences CBF in stroke patients may provide the foundation for novel therapeutic approaches to improve functional outcomes in stroke patients.

Cerebrovascular tone and resistance measures differ between healthy control and patients with acute intracerebral haemorrhage: exploratory analyses from the BREATHE-ICH study.

Objective.Cerebral autoregulation impairment in acute neurovascular disease is well described. The recent BREATHE-ICH study demonstrated improvements in dynamic cerebral autoregulation, by hypocapnia generated by hyperventilation, in the acute period following intracranial haemorrhage (ICH). This exploratory analysis of the BREATHE-ICH dataset aims to examine the differences in hypocapnic responses between healthy controls and patients with ICH, and determine whether haemodynamic indices differ between baseline and hypocapnic states.Approach.Acute ICH patients were recruited within 48 h of onset and healthy volunteers were recruited from a university setting. Transcranial Doppler measurements of the middle cerebral artery were obtained at baseline and then a hyperventilation intervention was used to induce hypocapnia. Patients with ICH were then followed up at 10-14 D post-event for repeated measurements.Main results.Data from 43 healthy controls and 12 patients with acute ICH met the criteria for statistical analysis. In both normocapnic and hypocapnic conditions, significantly higher critical closing pressure and resistance area product were observed in patients with ICH. Furthermore, critical closing pressure changes were observed to be sustained at 10-14 D follow up. During both the normocapnic and hypocapnic states, reduced autoregulation index was observed bilaterally in patients with ICH, compared to healthy controls.Significance.Whilst this exploratory analysis was limited by a small, non-age matched sample, significant differences between ICH patients and healthy controls were observed in factors associated with cerebrovascular tone and resistance. These differences suggest underlying cerebral autoregulation changes in ICH, which may play a pivotal role in the morbidity and mortality associated with ICH.

Clinical Relevance of Orthostatic Hypotension in Patients with Atrial Fibrillation and Suspected Transient Ischemic Attack.

INTRODUCTION: Orthostatic hypotension (OH) and atrial fibrillation (AF) are both regarded as independent risk factors for transient ischemic attack (TIA). However, the clinical implication of OH in the presence of AF is unclear. This study investigates, for the first time, the association between blood pressure (BP), OH and mortality in a cohort of patients with AF and TIA symptoms. AIM: To investigate the incidence of the association between OH, AF and TIA. METHODS: This retrospective observational study utilised the Leicester one-stop transient TIA clinic patient database to consider the initial systolic and diastolic BP of 688 patients with a diagnosis of AF. The primary outcome was time until death. Covariant measures included status of AF diagnosis (known or new AF), cardiovascular risk factors, and primary clinic diagnosis [cerebrovascular (CV) versus non-cerebrovascular (non-CV)]. Statistical models adjusted for sex, age, previous AF diagnosis. RESULTS: Mortality rate was higher in the over 85 age group [191.5 deaths per 1000 person years (py) (95% CI 154.0-238.1)] and lower in the aged 75 and younger age group [40.0 deaths per 1000 py (95% CI 27.0-59.2)] compared to intermediate groups. A 10 mmHg increase in supine diastolic BP was associated with a significant reduction in the hazard of mortality for patients suspected of TIA with AF [adjusted HR 0.79 (95% CI 0.68-0.92), p < 0.001]. The mortality rate for patients with OH was 119.0 deaths per 1000 py compared with a rate of 98.0 for patients without OH (rate ratio 1.2, p = 0.275). CONCLUSION: Higher diastolic BP may be a marker for reduced mortality risk in patients with a previous AF diagnosis and non-CV diagnosis. Lower diastolic BP and the presence of AF pertain to a higher mortality risk. This study raises the importance of opportunistic screening for both OH and AF in patients presenting to TIA clinic.