Total sleep deprivation alters endothelial function in rats: a nonsympathetic mechanism.

STUDY OBJECTIVES: Sleep loss is suspected to induce endothelial dysfunction, a key factor in cardiovascular risk. We examined whether sympathetic activity is involved in the endothelial dysfunction caused by total sleep deprivation (TSD). DESIGN: TWO GROUPS: TSD (24-h wakefulness), using slowly rotating wheels, and wheel control (WC). PARTICIPANTS: Seven-month-old male Wistar rats. INTERVENTIONS: Pharmacological sympathectomy (reserpine, 5 mg/kg, intraperitoneal), nitric oxide synthase (NOS) inhibition (N (G)-nitro-L-arginine, 20 mg/kg, intraperitoneally 30 min before experiment) and cyclooxygenase (COX) inhibition (indomethacin, 5 mg/kg, intraperitoneally 30 min before experiment). MEASUREMENTS AND RESULTS: In protocol 1, changes in heart rate (HR) and blood pressure were continuously recorded in the sympathectomized and non-sympathectomized rats. Blood pressure and HR increased during TSD in non-sympathectomized rats. In protocol 2, changes in skin blood flow (vasodilation) were assessed in the sympathectomized and non-sympathectomized rats using laser-Doppler flowmetry coupled with iontophoretic delivery of acetylcholine (ACh), sodium nitroprusside (SNP), and anodal and cathodal currents. ACh- and cathodal current-induced vasodilations were significantly attenuated after TSD in non-sympathectomized and sympathectomized rats (51% and 60%, respectively). In protocol 3, ACh-induced vasodilation was attenuated after NOS and COX inhibition (66% and 49%, respectively). Cathodal current-induced vasodilation decreased by 40% after COX inhibition. In TSD compared to WC a decrease in ACh-induced vasodilation was still observed after COX inhibition. No changes in SNP- and anodal current-induced vasodilation were detected. CONCLUSION: These results demonstrate that total sleep deprivation induces a reduction in endothelial-dependent vasodilation. This endothelial dysfunction is independent of blood pressure and sympathetic activity but associated with nitric oxide synthase and cyclooxygenase pathway alterations.

Effect of acute sleep deprivation on vascular function in healthy subjects.

Sleep disorders are associated with inflammation and sympathetic activation, which are suspected to induce endothelial dysfunction, a key factor in the increased risk of cardiovascular disease. Less is known about the early effects of acute sleep deprivation on vascular function. We evaluated microvascular reactivity and biological markers of endothelial activation during continuous 40 h of total sleep deprivation (TSD) in 12 healthy men (29 +/- 3 yr). The days before [day 1 (D1)] and during TSD (D3), at 1200 and 1800, endothelium-dependent and -independent cutaneous vascular conductance was assessed by iontophoresis of acetylcholine and sodium nitroprusside, respectively, coupled to laser-Doppler flowmetry. At 0900, 1200, 1500, and 1800, heart rate (HR) and instantaneous blood pressure (BP) were recorded in the supine position. At D1, D3, and the day after one night of sleep recovery (D4), markers of vascular endothelial cell activation, including soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and interleukin-6 were measured from blood samples at 0800. Compared with D1, plasma levels of E-selectin were raised at D3, whereas intercellular adhesion molecule-1 and interleukin-6 were raised at D4 (P < 0.05). The endothelium-dependent and -independent CVC were significantly decreased after 29 h of TSD (P < 0.05). By contrast, HR, systolic BP, and the normalized low-frequency component of HR variability (0.04-0.15 Hz), a marker of the sympathetic activity, increased significantly within 32 h of TSD (P < 0.05). In conclusion, acute exposure to 40 h of TSD appears to cause vascular dysfunction before the increase in sympathetic activity and systolic BP.

Prediction of performance level during a cognitive task from ongoing EEG oscillatory activities.

OBJECTIVE: Tracking the level of performance in cognitive tasks may be useful in environments, such as aircraft, in which the awareness of the pilots is critical for security. In this paper, the usefulness of EEG for the prediction of performance is investigated. METHODS: We present a new methodology that combines various ongoing EEG measurements to predict performance level during a cognitive task. We propose a voting approach that combines the outputs of elementary support vector machine (SVM) classifiers derived from various sets of EEG parameters in different frequency bands. The spectral power and phase synchrony of the oscillatory activities are used to classify the periods of rapid reaction time (RT) versus the slow RT responses of each subject. RESULTS: The voting algorithm significantly outperforms classical SVM and gives a good average classification accuracy across 12 subjects (71%) and an average information transfer rate (ITR) of 0.49bit/min. The main discriminating activities are laterally distributed theta power and anterio-posterior alpha synchronies, possibly reflecting the role of a visual-attentional network in performance. CONCLUSIONS: Power and synchrony measurements enable the discrimination between periods of high average reaction time versus periods of low average reaction time in a same subject. Moreover, the proposed approach is easy to interpret as it combines various types of measurements for classification, emphasizing the most informative. SIGNIFICANCE: Ongoing EEG recordings can predict the level of performance during a cognitive task. This can lead to real-time EEG monitoring devices for the anticipation of human mistakes.

Psychostimulants and G tolerance in rhesus monkeys: effects of oral modafinil and injected caffeine.

INTRODUCTION: Caffeine and modafinil are psychostimulants that may be taken by fighter aircraft pilots to reduce fatigue. Fighter pilots are subjected to high positive G loads that reduce cerebral blood flow and consequently may induce G-LOC. The aim of the experiment was to determine whether these drugs may reduce tolerance to G stress. METHODS: Seven adult male rhesus monkeys participated in the experiment. Five were equipped with ECoG and ECG wires and underwent two G tests (A and B). Each experiment consisted of five centrifuge runs. Before the runs, the monkeys received no drug (control) or were given either 7.5 mg x kg(-1) caffeine IM or 64 mg x kg(-1) modafinil PO or the corresponding vehicles. The runs were performed up to +13 Gz with an onset rate of 0.1 G x s(-1) (test A) or 3 G x s(-1) (test B). The run was ended when the electrical activity of one ECoG channel had disappeared (i.e., G-LOC). RESULTS: In experiment A, drug administration had no significant effect. In experiment B, the injection of the caffeine-free solvent caused a delay in G-LOC compared with the control condition (no administration). Caffeine solvent also induced an increase in plasma osmolality. DISCUSSION: Modafinil administration has no significant effect on the G tolerance of rhesus monkeys. Regarding caffeine, the drug seems to have caused the reverse effect compared with the solvent. CONCLUSIONS: Caffeine and modafinil administration had no significant effect on the G-tolerance of rhesus monkeys when compared with controls. This result needs to be confirmed in humans.

Electroencephalography (EEG) and somatosensory evoked potentials (SEP) to prevent cerebral ischaemia in the operating room.

We review the principal aspects of EEG and SEP to detect and prevent cerebral ischaemia in the operating room during interventions at risk. EEG and SEP are variables that indirectly reflect cerebral blood flow (CBF) provided that anaesthetic regimen, body temperature, and arterial blood pressure of the patient are stable. When CBF decreases and reaches the functional threshold, slowing and/or attenuation of EEG occurs while the amplitude and the latency of cortical SEP are, respectively decreased and lengthened. Based on these changes, numerous criteria corresponding to critical thresholds have been defined. A decrease in EEG amplitude greater than 30% or EEG changes lasting more than 30 s have been considered as significant by clinicians. The main criteria resulting from computerized EEG analysis were a reduction in total power and/or in spectral edge frequency. Regarding SEP, a more than 50% decrease in N20 amplitude and/or a more than 1 ms increase in central conduction time were the most frequently used criteria. According to the bulk of literature, it may be concluded that processed EEG analysis is more sensitive than visual EEG analysis to detect cerebral ischaemia, and that SEP are not less sensitive than conventional EEG. Moreover, literature shows that SEP are as specific as computerized EEG analysis to disclose ischaemia during carotid endarterectomy.

Cerebral hemodynamics and brain oxygen changes related to gravity-induced loss of consciousness in rhesus monkeys.

The aim of the present experiment was to study the influence of +Gz acceleration (head-to-foot inertial forces) onset on cerebral oxygenation changes (cerebral oxy- and deoxy-hemoglobin) and cerebral blood volume (CBV) in order to evaluate the role of cerebral hypoxemia and ischemia in the appearance of +Gz-induced loss of consciousness (G-LOC). We used five rhesus monkeys which were equipped with near infrared spectroscopy optodes fixed onto the parietooccipital cranial bone. G-LOC (isoelectric electrocorticogram) was detected with silver balls electrodes in contact with the dura matter. The animals were centrifuged up to +12 Gz with two onset rates (0.1 and 3 G/s). Cerebral deoxy-hemoglobin increased significantly (max: +30 +/- 6% of control, P < 0.01) only during the 0.1 G/s run. At G-LOC, CBV changes were not related to G-onset rate (P = 0.30; mean change: -32 +/- 6% of control). We conclude that cerebral ischemia is the main mechanism in the occurrence of G-LOC.