Functional connectome of arousal and motor brainstem nuclei in living humans by 7 Tesla resting-state fMRI.

Brainstem nuclei play a pivotal role in many functions, such as arousal and motor control. Nevertheless, the connectivity of arousal and motor brainstem nuclei is understudied in living humans due to the limited sensitivity and spatial resolution of conventional imaging, and to the lack of atlases of these deep tiny regions of the brain. For a holistic comprehension of sleep, arousal and associated motor processes, we investigated in 20 healthy subjects the resting-state functional connectivity of 18 arousal and motor brainstem nuclei in living humans. To do so, we used high spatial-resolution 7 Tesla resting-state fMRI, as well as a recently developed in-vivo probabilistic atlas of these nuclei in stereotactic space. Further, we verified the translatability of our brainstem connectome approach to conventional (e.g. 3 Tesla) fMRI. Arousal brainstem nuclei displayed high interconnectivity, as well as connectivity to the thalamus, hypothalamus, basal forebrain and frontal cortex, in line with animal studies and as expected for arousal regions. Motor brainstem nuclei showed expected connectivity to the cerebellum, basal ganglia and motor cortex, as well as high interconnectivity. Comparison of 3 Tesla to 7 Tesla connectivity results indicated good translatability of our brainstem connectome approach to conventional fMRI, especially for cortical and subcortical (non-brainstem) targets and to a lesser extent for brainstem targets. The functional connectome of 18 arousal and motor brainstem nuclei with the rest of the brain might provide a better understanding of arousal, sleep and accompanying motor functions in living humans in health and disease.

Creatine deficiency and heart failure.

Impaired cardiac energy metabolism has been proposed as a mechanism common to different heart failure aetiologies. The energy-depletion hypothesis was pursued by several researchers, and is still a topic of considerable interest. Unlike most organs, in the heart, the creatine kinase system represents a major component of the metabolic machinery, as it functions as an energy shuttle between mitochondria and cytosol. In heart failure, the decrease in creatine level anticipates the reduction in adenosine triphosphate, and the degree of myocardial phosphocreatine/adenosine triphosphate ratio reduction correlates with disease severity, contractile dysfunction, and myocardial structural remodelling. However, it remains to be elucidated whether an impairment of phosphocreatine buffer activity contributes to the pathophysiology of heart failure and whether correcting this energy deficit might prove beneficial. The effects of creatine deficiency and the potential utility of creatine supplementation have been investigated in experimental and clinical models, showing controversial findings. The goal of this article is to provide a comprehensive overview on the role of creatine in cardiac energy metabolism, the assessment and clinical value of creatine deficiency in heart failure, and the possible options for the specific metabolic therapy.

Medium-term effect of sublingual l-glutathione supplementation on flow-mediated dilation in subjects with cardiovascular risk factors.

OBJECTIVE: Supplementation of glutathione (GSH) may be a positive strategy to improve the endogenous antioxidant defense required to counteract many acute and chronic diseases. However, the efficacy of GSH treatment seems to be closely related to type of administration, degree of absorption, and increase of its concentrations. The aim of this study was to test a new sublingual formulation of L-GSH, which enters directly the systemic circulation, to assess its efficacy on circulating biochemical markers of hepatic metabolism, lipid profile, and oxidative stress and on peripheral vascular function compared with placebo in patients with cardiovascular risk factors (CVRF). METHODS: We enrolled 16 healthy men with CVRF in a double-blinded, randomized placebo-controlled crossover study. At each visit, blood samples were collected for biochemistry analyses and peripheral endothelial function (reactive hyperemia index [RHI]) and stiffness were measured by Endo-PAT2000. RESULTS: In the overall population, a decrease in total and low-density lipoprotein cholesterol was highlighted after L-GSH supplementation compared with placebo (P = 0.023 and P = 0.04, respectively). On the contrary, no difference was observed in RHI and oxidative stress markers between L-GSH and placebo in the study population. However, seven participants with baseline abnormal RHI (≤1.67) compared with those with normal RHI showed a significant reduction of arterial stiffness after L-GSH administration, (P = 0.007 and P = 0.037, respectively). CONCLUSIONS: Supplementation of L-GSH compared with placebo influences the lipid profile of patients with CVRF. Sublingual L-GSH may represent a valid prevention of vascular damage in patients with CVRF and endothelial dysfunction.

Correlational analysis of electroencephalographic and end-tidal carbon dioxide signals during breath-hold exercise.

The central mechanism of breathing control is not totally understood. Several studies evaluated the correlation between electroencephalographic (EEG) power spectra and respiratory signals by performing resting state tasks or adopting hypercapnic/hypoxic stimuli. The observation of brain activity during voluntary breath hold tasks, might be an useful approach to highlight the areas involved in mechanism of breath regulation. Nevertheless, studies of brain activity with EEG could present some limitations due to presence of severe artifacts. When artifact rejection methods, as independent component analysis, cannot reliably clean EEG data, it is necessary to exclude noisy segments. In this study, global field power in the delta band and end-tidal CO2 were derived from EEG and CO2 signals respectively in 4 healthy subjects during a breath-hold task. The cross correlation function between the two signals was estimated taking into account the presence of missing samples. The statistical significance of the correlation coefficients at different time lags was assessed using surrogate data. Some simulations are introduced to evaluate the effect of missing data on the correlational analysis and their results are discussed. Results obtained on subjects show a significant correlation between changes in EEG power in the delta band and end-tidal CO2. Moreover, the changes in end-tidal CO2 were found to precede those of global field power. These results might help to better understand the cortical mechanisms involved in the control of breathing.

[Recent knowledges on chemosensitivity to hypoxia and hypercapnia in cardiovascular disease]. / Recenti conoscenze sulla sensibilità chemocettiva ad ipossia ed ipercapnia in patologia cardiovascolare.

The pathophysiologic role of enhanced chemosensitivity to carbon dioxide and/or hypoxia has been underscored in several cardiovascular diseases, including heart failure. In the early stages of this syndrome, the chemoreflex acts as a compensatory mechanism. Later on, however, it contributes to sustain the sympathetic activation, with detrimental effects on cardiovascular function and prognosis.

Reduced hypoxic ventilatory response with preserved blood oxygenation in yoga trainees and Himalayan Buddhist monks at altitude: evidence of a different adaptive strategy?

Yoga induces long-term changes in respiratory function and control. We tested whether it represents a successful strategy for high-altitude adaptation. We compared ventilatory, cardiovascular and hematological parameters in: 12 Caucasian yoga trainees and 12 control sea-level residents, at baseline and after 2-week exposure to high altitude (Pyramid Laboratory, Nepal, 5,050 m), 38 active lifestyle high-altitude natives (Sherpas) and 13 contemplative lifestyle high-altitude natives with practice of yoga-like respiratory exercises (Buddhist monks) studied at 5,050 m. At baseline, hypoxic ventilatory response (HVR), red blood cell count and hematocrit were lower in Caucasian yoga trainees than in controls. After 14 days at altitude, yoga trainees showed similar oxygen saturation, blood pressure, RR interval compared to controls, but lower HVR (-0.44 +/- 0.08 vs. -0.98 +/- 0.21 l/min/m/%SaO(2), P < 0.05), minute ventilation (8.3 +/- 0.9 vs. 10.8 +/- 1.6 l/min, P < 0.05), breathing rate (indicating higher ventilatory efficiency), and lower red blood cell count, hemoglobin, hematocrit, albumin, erythropoietin and soluble transferrin receptors. Hypoxic ventilatory response in monks was lower than in Sherpas (-0.23 +/- 0.05 vs. -0.63 +/- 0.09 l/min/m/%SaO(2), P < 0.05); values were similar to baseline data of yoga trainees and Caucasian controls, respectively. Red blood cell count and hematocrit were lower in monks as compared to Sherpas. In conclusion, Caucasian subjects practicing yoga maintain a satisfactory oxygen transport at high altitude, with minimal increase in ventilation and with reduced hematological changes, resembling Himalayan natives. Respiratory adaptations induced by the practice of yoga may represent an efficient strategy to cope with altitude-induced hypoxia.