Aging affects the phase coherence between spontaneous oscillations in brain oxygenation and neural activity.

The risk of neurodegenerative disorders increases with age, due to reduced vascular nutrition and impaired neural function. However, the interactions between cardiovascular dynamics and neural activity, and how these interactions evolve in healthy aging, are not well understood. Here, the interactions are studied by assessment of the phase coherence between spontaneous oscillations in cerebral oxygenation measured by fNIRS, the electrical activity of the brain measured by EEG, and cardiovascular functions extracted from ECG and respiration effort, all simultaneously recorded. Signals measured at rest in 21 younger participants (31.1 ± 6.9 years) and 24 older participants (64.9 ± 6.9 years) were analysed by wavelet transform, wavelet phase coherence and ridge extraction for frequencies between 0.007 and 4 Hz. Coherence between the neural and oxygenation oscillations at ∼ 0.1 Hz is significantly reduced in the older adults in 46/176 fNIRS-EEG probe combinations. This reduction in coherence cannot be accounted for in terms of reduced power, thus indicating that neurovascular interactions change with age. The approach presented promises a noninvasive means of evaluating the efficiency of the neurovascular unit in aging and disease.

Glyceryl trinitrate-induced blood pressure variability decrease during head-up tilt test predicts vasovagal response.

PURPOSE: Glyceryl trinitrate (GTN) provoked cardioinhibitory syncope during the head-up tilt test is preceded by a period of disrupted blood pressure variability (BPV). Endogenous nitric oxide (NO) attenuates BPV independently of blood pressure (BP). We hypothesized that exogenous NO donor GTN might decrease BPV during the presyncope period. A decrease in BPV may predict the tilt outcome. METHODS: We analyzed 29 tilt test recordings of subjects with GTN-induced cardioinhibitory syncope and 30 recordings of negative subjects. A recursive autoregressive model of BPV after GTN was performed; powers of the respiratory (0.15-0.45 Hz) and nonrespiratory frequency (0.01-0.15 Hz) bands were calculated for each of the 20 normalized time periods. The post-GTN relative changes in heart rate, BP, and BPV were calculated. RESULTS: In the syncope group, spectral power of nonrespiratory frequency systolic and diastolic BPV progressively felt for 30% after GTN application and stabilized after 180 s. BP started to fall 240 s after the GTN application. Decrease in nonrespiratory frequency power of diastolic BPV 20 s after GTN administration predicted cardioinhibitory syncope (area under the curve 0.811; 77% sensitivity; 70% specificity; cutoff value > 7%). CONCLUSION: GTN application during the tilt test attenuates systolic and diastolic nonrespiratory frequency BPV during the presyncope period, independent of BP. A decrease in nonrespiratory frequency diastolic BPV 20 s after GTN application predicts cardioinhibitory syncope with good sensitivity and moderate specificity.

Hemodynamic responses to low-level transcutaneous auricular nerve stimulation in young volunteers.

Objectives: The aim of this study was to characterize cardiovascular autonomic responses during two constant current intensities below sensory threshold of transcutaneous auricular nerve stimulation (taNS). On this basis, a protocol for taNS with autonomic modulatory potential could be proposed. Subjects and methods: We included 26 men and 24 women, mean age 26. Data were collected during three randomly allocated 20-minute right tragus stimulation sessions - a) no-stimulation (sham), b) 90 µA (arbitrary), and c) 130 µA (near the lowest sensory threshold in majority). Stimulation was 20 Hz, rectangular pulse width of 2 ms, duty cycle 2-second on/off. To assess autonomic responses, we continuously recorded ECG, non-invasive arterial blood pressure (BP) and thoracic impedance cardiography data. Ten-minute data were compared. Fast Fourier transform of RR intervals was performed on 10-minute recordings as well. Low frequency and high frequency power spectra were calculated. Friedman test or one-way ANOVA for repeated measurements and Mann-Whitney or Wilcoxon's signed-rank test, or t-test were carried out. P < 0.05 was considered significant. Results: At 130 µA stimulation, cardiac output significantly decreased (p < 0.05), driven by significant heart rate drop in women, and stroke volume and contractility drop in men, pointing to a gender-related autonomic responses. We observed no significant changes in BP, or variability parameters. Significantly higher body size and BP were found in men, as expected. Conclusions: It seems that tested taNS protocol has a potential for cardiac autonomic modulation in majority of young healthy men as well as women. Further studies are however needed to prove the therapeutic potential of this stimulation protocol in different patient groups.

Cardiovascular responses to low-level transcutaneous vagus nerve stimulation.

AIMS: The aim was to determine cardiovascular responses to an arbitrary protocol of transcutaneous low-level vagus nerve electrical stimulation (tVNS). METHODS: Study was performed in 15 male volunteers, mean age 23 years. Data were collected during two sessions - sham stimulation (no stimulation) and stimulation. Each session included one-hour resting phase followed by 15-min autonomic nervous system testing phase (Valsalva, deep breathing, wet-cold face tests), all in supine position. The right tragus stimulation parameters were: 20 Hz, constant current at sensation threshold, 1 ms rectangular pulse width. The ECG, noninvasive arterial blood pressure and thoracic impedance cardiography measurements were recorded and analyzed continuously with the Task Force® Monitor (CNSystems Medizintechnik GmbH, Graz, Ver. 2.2.10.0). t-Test for paired samples, paired Wilcoxon signed-rank, and one-way ANOVA for repeated measurements were carried out. P < 0.05 was considered significant. RESULTS: We demonstrated significant reductions of left ventricular contractility and output parameters, a trend for heart rate reduction, and resulting beneficial reduction of left ventricular work load. However, significant increases of blood pressure and total peripheral resistance were recognized, possibly as a reflex response. CONCLUSION: It seems that our tVNS protocol has a potential for cardiac autonomic modulation. This gives us opportunity to advance our stimulation parameters with participant-specific adjustments. Further studies are however needed to prove the therapeutic potential of such approach in different patient groups.

The diabetic brain and cognition.

The prevalence of both Alzheimer's disease (AD) and vascular dementia (VaD) is increasing with the aging of the population. Studies from the last several years have shown that people with diabetes have an increased risk for dementia and cognitive impairment. Therefore, the authors of this consensus review tried to elaborate on the role of diabetes, especially diabetes type 2 (T2DM) in both AD and VaD. Based on the clinical and experimental work of scientists from 18 countries participating in the International Congress on Vascular Disorders and on literature search using PUBMED, it can be concluded that T2DM is a risk factor for both, AD and VaD, based on a pathology of glucose utilization. This pathology is the consequence of a disturbance of insulin-related mechanisms leading to brain insulin resistance. Although the underlying pathological mechanisms for AD and VaD are different in many aspects, the contribution of T2DM and insulin resistant brain state (IRBS) to cerebrovascular disturbances in both disorders cannot be neglected. Therefore, early diagnosis of metabolic parameters including those relevant for T2DM is required. Moreover, it is possible that therapeutic options utilized today for diabetes treatment may also have an effect on the risk for dementia. T2DM/IRBS contribute to pathological processes in AD and VaD.

Resting heart rate variability and heart rate recovery after submaximal exercise.

PURPOSE: Aerobic training accelerates Heart Rate Recovery after exercise in healthy subjects and in patients with coronary disease. As shown by pharmacological autonomic blockade, HRR early after exercise is dependent primarily on parasympathetic reactivation. Thus, accelerated HRR early after exercise in endurance-trained athletes may be attributed to augmented parasympathetic reactivation. In the present study, we tested the hypothesis that the HRR early after submaximal exercise is related to the pre-exercise parasympathetic modulation. METHODS: Thirty endurance-trained athletes (20 males, 50 ± 7 years) and thirty control subjects (20 males, 52 ± 6 years) performed a submaximal exercise on a cyclo-ergometer. Pre-exercise resting short-term heart rate variability (HRV) parameters in time and frequency-domains were correlated with HRR during the first 30 s, 1 and 2 min after cessation of exercise. RESULTS: We found that HRR was statistically significantly faster in athletes than in controls at all examination time points (p < 0.05). HF, SDNN and RMSSD were statistically significantly higher in athletes than in controls (p < 0.05), but other resting HRV parameters were not statistically different between groups. After 30 s, 1 and 2 min of recovery, HRR correlation with total power, HF, HFnu and RMSSD was positive, while the correlation with LF/HF was negative for small and positive for larger values. The opposite was true for SDNN. CONCLUSIONS: These findings support the hypothesis that HRR early after submaximal exercise is related to resting parasympathetic modulation in the middle-aged subjects. In addition, they suggested an optimal range of HRV for maximal HRR after exercise.

Comparison of active standing test, head-up tilt test and 24-h ambulatory heart rate and blood pressure monitoring in diagnosing postural tachycardia.

Protocols for the assessment of postural tachycardia differ in both type of orthostatic challenge and test duration. We therefore compared heart rate (HR) and blood pressure responses during an active standing test (AST) and a head-up tilt test (HUT) in 34 patients with orthostatic intolerance and 31 asymptomatic subjects. A subset also performed 24-h ambulatory blood pressure monitoring (ABPM). HR responses were similar between AST and HUT both in asymptomatic and in orthostatic intolerant subjects. Specificity of HR increase ≥30 bpm for orthostatic intolerance was high (above 0.85) with both AST and HUT and was similar at 3 minutes and at 9 minutes. HR changes recorded during self-performed AST (in the context of 24-h ABPM) and circadian HR difference corresponded well to changes recorded during AST in the autonomic laboratory. We conclude that AST and HUT are comparable methods for the assessment of postural tachycardia, that 3-min and 9-min tests are appropriate, and that ABPM is a useful ancillary test in the assessment of orthostatic responses.

Importance of erythropoietin in brain protection after cardiac surgery: a pilot study.

BACKGROUND: Neurologic complications after cardiac operations present an important medical problem, as well as a financial burden. They increase the morbidity and hospital stays of patients who have otherwise undergone successful heart operations. The current protocols for perioperative brain protection against ischemic events are not optimal. Because of its different pleiotropic mechanisms of action, recombinant human erythropoietin might provide neuroprotection. METHODS: In this study, we included 20 patients who were older than 18 years and required surgical revascularization of the heart with the use of the heart-lung machine. Ten patients received 3 consecutive intravenous doses (24,000 IU) of recombinant human erythropoietin (rHuEpo). Neurologic and magnetic resonance imaging (MRI) examinations were done before and in the first 5 days after surgery. RESULTS: The erythropoietin-treated and control groups were comparable with respect to study protocol outcomes: number of coronary artery bypass grafts (3.3 and 3.2 grafts/patient, respectively), operative time (4.12 and 4.6 hours), and transfusion volume per patient (708 and 674 mL). The groups were also comparable with respect to blood pressure values at all stages of the operation. MRI scans revealed that 4 of 10 patients from the control group had fresh ischemic brain lesions after open heart surgery. None of the patients in the erythropoietin-treated group had fresh ischemic brain lesions. CONCLUSION: Although the number of patients was small, the results regarding brain protection with rHuEpo are encouraging. rHuEpo is a promising neuroprotective agent.