A Systems Biology Strategy on Differential Gene Expression Data Discloses Some Biological Features of Atrial Fibrillation

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with extensive structural, contractile, and electrophysiological remodeling. In this manuscript we re-analyzed gene expression data from a microarray experiment on AF patients and control tissues, using a new paradigm based on a posteriori unsupervised strategy in which the discrimination of patients comes out from purely syntactical premises. This paradigm, more adherent to biological reality where genes work in highly connected networks, allowed us to get both a very precise patients/control discrimination and the discovery of cell adhesion/tissue modeling and inflammation processes as the main dimensions of AF

Quantification of not-dipolar components of atrial depolarization by principal component analysis of the P-wave

BACKGROUND: Principal component analysis (PCA) of the T-wave has been demonstrated to quantify the dipolar and not-dipolar components of the ventricular activation, the latter reflecting repolarization heterogeneity. Accordingly, the PCA of the P-wave could help in analyzing the heterogeneous propagation of sinus impulses in the atria, which seems to predispose to fibrillation. AIM: The aim of this study is to perform the PCA of the P-wave in patients prone to atrial fibrillation (AF). METHODS: PCA is performed on P-waves extracted by averaging technique from ECG recordings acquired using a 32-lead mapping system (2048 Hz, 24 bit, 0-400 Hz bandwidth). We extracted PCA parameters related to the dipolar and not dipolar components of the P-wave using the first 3 eigenvalues and the cumulative percent of variance explained by the first 3 PCs (explained variance EV). RESULTS AND CONCLUSIONS: We found that the EV associated to the low risk patients is higher than that associated to the high risk patients, and that, correspondingly, the first eigenvalue is significantly lower while the second one is significantly higher in the high risk patients respect to the low risk group. Factor loadings showed that on average all leads contribute to the first principal component

P-wave Variability and Atrial Fibrillation

The analysis of P-wave template has been widely used to extract indices of Atrial Fibrillation (AF) risk stratification. The aim of this paper was to assess the potential of the analysis of the P-wave variability over time in patients suffering from atrial fibrillation. P-wave features extracted from P-wave template together with novel indices of P-wave variability have been estimated in a population of patients suffering from persistent AF and compared to those extracted from control subjects. We quantify the P-wave variability over time using three algorithms and we extracted three novel indices: one based on the cross-correlation coefficients among the P-waves (Cross-Correlation Index, CCI), one associated to variation in amplitude of the P-waves (Amplitude Dispersion Index, ADI), one sensible to the phase shift among P-waves (Warping Index, WI). The control group resulted to be characterized by shorter P-wave duration and by a less amount of fragmentation and variability, respect to AF patients. The parameter CCI shows the highest sensitivity (97.3%) and a good specificity (95%)

Brain-heart pathways to blood pressure-related hypoalgesia

OBJECTIVE: High blood pressure (BP) is associated with reduced pain sensitivity, known as BP-related hypoalgesia. The underlying neural mechanisms remain uncertain, yet arterial baroreceptor signaling, occurring at cardiac systole, is implicated. We examined normotensives using functional neuroimaging (fMRI) and pain stimulation during distinct phases of the cardiac cycle to test the hypothesized neural mediation of baroreceptor-induced attenuation of pain. METHODS: Eighteen participants (10 women; 32.7 ± 6.5 years) underwent BP monitoring over one week at home, and individual pain thresholds were determined in the lab. Subsequently, participants were administered unpredictable painful and non-painful electrocutaneous shocks (stimulus type), timed to occur either at systole or diastole (cardiac phase) in an event-related design. After each trial, participants evaluated their subjective experience. RESULTS: Subjective pain was lower for painful stimuli administered at systole compared to diastole, F1, 2283 = 4.82; p = 0.03. Individuals with higher baseline BP demonstrated overall lower pain perception, F1, 2164 = 10.47; p < 0.0001. Within the brain, painful stimulation activated somatosensory areas, prefrontal cortex, cingulate cortex, posterior insula, amygdala, and the thalamus. Stimuli delivered during systole (concurrent with baroreceptor discharge) activated areas associated with heightened parasympathetic drive. No stimulus type x cardiac phase interaction emerged except for a small cluster located in the right parietal cortex. CONCLUSIONS: We confirm the negative associations between BP and pain, highlighting the antinociceptive impact of baroreceptor discharge. Neural substrates associated with baroreceptor/BP-related hypoalgesia include superior parietal lobule, precentral and lingual gyrus, regions typically involved in the cognitive aspects of pain experience

MRI-Induced Heating on Patients with Implantable Cardioverter-Defibrillators and Pacemaker: Role of the Lead Structure

Abstract Magnetic Resonance Imaging (MRI

Complexity of MRI induced heating on metallic leads: Experimental measurements of 374 configurations

<p>Abstract</p> <p>Background</p> <p>MRI induced heating on PM leads is a very complex issue. The widely varying results described in literature suggest that there are many factors that influence the degree of heating and that not always are adequately addressed by existing testing methods.</p> <p>Methods</p> <p>We present a wide database of experimental measurements of the heating of metallic wires and PM leads in a 1.5 T RF coil. The aim of these measurements is to systematically quantify the contribution of some potential factors involved in the MRI induced heating: the length and the geometric structure of the lead; the implant location within the body and the lead path; the shape of the phantom used to simulate the human trunk and its relative position inside the RF coil.</p> <p>Results</p> <p>We found that the several factors are the primary influence on heating at the tip. Closer locations of the leads to the edge of the phantom and to the edge of the coil produce maximum heating. The lead length is the other crucial factor, whereas the implant area does not seem to have a major role in the induced temperature increase. Also the lead structure and the geometry of the phantom revealed to be elements that can significantly modify the amount of heating.</p> <p>Conclusion</p> <p>Our findings highlight the factors that have significant effects on MRI induced heating of implanted wires and leads. These factors must be taken into account by those who plan to study or model MRI heating of implants. Also our data should help those who wish to develop guidelines for defining safe medical implants for MRI patients. In addition, our database of the entire set of measurements can help those who wish to validate their numerical models of implants that may be exposed to MRI systems.</p

A new insight on postural tachycardia syndrome in 102 adults with hypermobile Ehlers-Danlos Syndrome/hypermobility spectrum disorder

There is an association between joint hypermobility, hypermobile Ehlers-Danlos syndrome (hEDS) and different forms of orthostatic intolerance. Objective: to explore autonomic profile in a large cohort of adults with hEDS and hypermobility spectrum disorder (hEDS/HSD) with a multimodal approach. In this observational retrospective study, heart rate, blood pressure and baroreflex sensitivity were estimated in 102 hEDS/HSD subjects during deep breathing, Valsalva maneuver, standing up: 30-15 ratio, Head-Up Tilt and sustained handgrip. Abnormal results and head-up tilt test were common and included postural orthostatic tachycardia syndrome (POTS; 48%), orthostatic intolerance (25.5%) and hypotension (3.9%). Baroreflex sensitivity was significantly different in individuals with POTS compared to the others. This study confirms the high rate and heterogeneity of abnormal autonomic regulation in hEDS/HSD, and suggests the baroreflex sensitivity might distinguish comorbid POTS from other profiles in this subgroup of patients. Abnormal autonomic regulation is common in adults with hEDS/HSD and should be regularly assessed for tailoring the management approach

Linking Pain Sensation to the Autonomic Nervous System: The Role of the Anterior Cingulate and Periaqueductal Gray Resting-State Networks.

There are bi-directional interactions between the autonomic nervous system (ANS) and pain. This is likely underpinned by a substantial overlap between brain areas of the central autonomic network and areas involved in pain processing and modulation. To date, however, relatively little is known about the neuronal substrates of the ANS-pain association. Here, we acquired resting state fMRI scans in 21 healthy subjects at rest and during tonic noxious cold stimulation. As indicators of autonomic function, we examined how heart rate variability (HRV) frequency measures were influenced by tonic noxious stimulation and how these variables related to participants' pain perception and to brain functional connectivity in regions known to play a role in both ANS regulation and pain perception, namely the right dorsal anterior cingulate cortex (dACC) and periaqueductal gray (PAG). Our findings support a role of the cardiac ANS in brain connectivity during pain, linking functional connections of the dACC and PAG with measurements of low frequency (LF)-HRV. In particular, we identified a three-way relationship between the ANS, cortical brain networks known to underpin pain processing, and participants' subjectively reported pain experiences. LF-HRV both at rest and during pain correlated with functional connectivity between the seed regions and other cortical areas including the right dorsolateral prefrontal cortex (dlPFC), left anterior insula (AI), and the precuneus. Our findings link cardiovascular autonomic parameters to brain activity changes involved in the elaboration of nociceptive information, thus beginning to elucidate underlying brain mechanisms associated with the reciprocal relationship between autonomic and pain-related systems

Effect of parasympathetic stimulation on brain activity during appraisal of fearful expressions

Autonomic nervous system activity is an important component of human emotion. Mental processes influence bodily physiology, which in turn feeds back to influence thoughts and feelings. Afferent cardiovascular signals from arterial baroreceptors in the carotid sinuses are processed within the brain and contribute to this two-way communication with the body. These carotid baroreceptors can be stimulated non-invasively by externally applying focal negative pressure bilaterally to the neck. In an experiment combining functional neuroimaging (fMRI) with carotid stimulation in healthy participants, we tested the hypothesis that manipulating afferent cardiovascular signals alters the central processing of emotional information (fearful and neutral facial expressions). Carotid stimulation, compared with sham stimulation, broadly attenuated activity across cortical and brainstem regions. Modulation of emotional processing was apparent as a significant expression-by-stimulation interaction within left amygdala, where responses during appraisal of fearful faces were selectively reduced by carotid stimulation. Moreover, activity reductions within insula, amygdala, and hippocampus correlated with the degree of stimulation-evoked change in the explicit emotional ratings of fearful faces. Across participants, individual differences in autonomic state (heart rate variability, a proxy measure of autonomic balance toward parasympathetic activity) predicted the extent to which carotid stimulation influenced neural (amygdala) responses during appraisal and subjective rating of fearful faces. Together our results provide mechanistic insight into the visceral component of emotion by identifying the neural substrates mediating cardiovascular influences on the processing of fear signals, potentially implicating central baroreflex mechanisms for anxiolytic treatment targets

Ritmi e complessita' nello studio dei segnali del controllo autonomico nel sistema cardiovascolare

Dottorato di ricerca in bioingegneria. 9. ciclo. Supervisori S. Cerutti e S. Salinari. Controrelatore E. BelardinelliConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal