Pulse photoplethysmographic amplitude and heart rate variability during laparoscopic cholecystectomy: A prospective observational study.

BACKGROUND: Surgical stress affects the autonomic nervous system by increasing sympathetic outflow. One method of monitoring sympathetic activity is pulse photoplethysmographic analysis. From this two indices can be derived - autonomic nervous system state (ANSS) and ANSS index (ANSSi). It has recently been claimed that these indices can be used to measure sympathetic activity in anaesthetised patients, but their validity has not yet been demonstrated. OBJECTIVE: To measure changes in pulse photoplethysmographic indices and determine any agreement with autonomic nervous system modulation of the cardiovascular system in healthy study participants during surgery under general anaesthesia. DESIGN: Prospective observational study. SETTING: Single-centre study based at a tertiary care centre in Milan, Italy. PATIENTS: Healthy patients undergoing general anaesthesia for elective laparoscopic cholecystectomy. INTERVENTIONS: ANSS, ANSSi, and heart rate variability (HRV) were analysed at three main times: baseline, after induction of general anaesthesia, and after pneumoperitoneum insufflation. MAIN OUTCOME MEASURES: The magnitude of changes in photoplethysmographic and HRV indices was measured. The agreement between pulse photoplethysmographic and HRV-derived indices was assessed by Bland-Altman plots. RESULTS: In total, 52 patients were enrolled and their data analysed. Both pulse photoplethysmographic and HRV indices changed during the study phases. An agreement was found between ANSSi and low frequency spectral components of HRV [bias 10.2nu, 95% confidence interval (CI) -13 to 33.4], high frequency spectral components of HRV (bias 6.1 nu, 95% CI -16.3 to 28.6), and low frequency/high frequency ratio (bias 16.1nu, 95% CI -1.4 to 33.5). The agreement was weaker between ANSSI and HRV indices. CONCLUSION: The study endorses the use of pulse photoplethysmographic indices ANSS and ANSSi as surrogates to estimate changes of autonomic modulation of the cardiovascular system in healthy adults during surgery under general anaesthesia.Orcid ID: orcid.org/0000-0002-9616-803X.

Calibrated variability of muscle sympathetic nerve activity during graded head-up tilt in humans and its link with noradrenaline data and cardiovascular rhythms.

Muscle sympathetic nerve activity (MSNA) variability is traditionally computed through a low-pass filtering procedure that requires normalization. We proposed a new beat-to-beat MSNA variability computation that preserves dimensionality typical of an integrated neural discharge (i.e., bursts per unit of time). The calibrated MSNA (cMSNA) variability technique is contrasted with the traditional uncalibrated MSNA (ucMSNA) version. The powers of cMSNA and ucMSNA variabilities in the low-frequency (LF, from 0.04 to 0.15 Hz) band were computed with those of the heart period (HP) of systolic and diastolic arterial pressure (SAP and DAP, respectively) in seven healthy subjects (age, 20-28 years; median, 22 years; 5 women) during a graded head-up tilt. Subjects were sequentially tilted at 0°, 20°, 30°, 40°, and 60° table inclinations. The LF powers of ucMSNA and HP variabilities were expressed in normalized units (LFnu), whereas all remaining spectral markers were expressed in absolute units. We found that 1) the LF power of cMSNA variability was positively correlated with tilt angle, whereas the LFnu power of the ucMSNA series was uncorrelated; 2) the LF power of cMSNA variability was correlated with LF powers of SAP and DAP, LFnu power of HP and noradrenaline concentration, whereas the relationship of the LFnu power of ucMSNA variability to LF powers of SAP and DAP was weaker and that to LFnu power of HP was absent; and 3) the stronger relationship of cMSNA variability to SAP and DAP spectral markers compared with the ucMSNA series was confirmed individually. The cMSNA variability appears to be more suitable in describing sympathetic control in humans than traditional ucMSNA variability.

Cardiovascular control in women with fibromyalgia syndrome: do causal methods provide nonredundant information compared with more traditional approaches?

The cardiovascular autonomic control and the baroreflex sensitivity (BRS) have been widely studied in fibromyalgia syndrome (FMS) patients through the computation of linear indices of spontaneous heart period (HP) and systolic arterial pressure (SAP) variabilities. However, there are many methodological difficulties regarding the quantification of BRS by the traditional indices especially in relation to the issue of causality. This difficulty has been directly tackled via a model-based approach describing the closed-loop HP-SAP interactions and the exogenous influences of respiration. Therefore, we aimed to assess whether the BRS assessed by the model-based causal closed-loop approach during supine and active standing in patients with FMS could provide complementary information to those obtained by traditional indices based on time and frequency domains. The findings of this study revealed that, at difference with the traditional methods to quantify BRS, the causality analysis applied to the HP, SAP, and respiratory series, through the model-based closed-loop approach, detected lower BRS in supine position, as well as a blunted response to the orthostatic stimulus in patients with FMS compared with healthy control subjects. Also, the strength of the causal relation from SAP to HP (i.e., along the cardiac baroreflex) increased during the active standing only in the control subjects. The model-based closed-loop approach proved to provide important complementary information about the cardiovascular autonomic control in patients with FMS.

Pulse Photoplethysmographic Analysis Estimates the Sympathetic Activity Directed to Heart and Vessels.

BACKGROUND: Novel pulse photoplethysmographic-derived indices have been proposed as tools to measure autonomic nervous system (ANS) modulation in anesthetized and awake patients, but nowadays their experimental validation is lacking. The authors aimed to investigate the ability of pulse photoplethysmographic amplitude (PPGA), ANS state (ANSS), and ANSS index (ANSSi) to measure changes of ANS modulation in response to sympathetic stimulation. METHODS: Ten awake healthy volunteers underwent two passive head-up tilts at 45° and 90°. The heart rate variability (HRV) and systolic arterial pressure variability were analyzed in the frequency domain as a measure of ANS modulation directed to the heart and the vessels. HRV, baroreflex sensitivity, and pulse photoplethysmographic indices were measured at baseline and after tilt maneuvers. The agreement between HRV-derived indices and pulse photoplethysmographic indices was assessed using Bland-Altman plots. RESULTS: PPGA, ANSS, and ANSSi changed significantly during the study protocol. Head-up tilt decreased PPGA and ANSS and increased ANNSi. There was a good agreement between ANSSi and baroreflex sensitivity explored in the high-frequency band (bias, 0.23; 95% CI, -22.7 to 23.2 normalized units) and between ANSSi and the sympathovagal modulation directed to the heart (bias, 0.96; 95% CI, -8.7 to 10.8 normalized units). CONCLUSIONS: In controlled experimental conditions, novel pulse plethysmographic indices seem to estimate the changes of the sympathetic outflow directed to the vessels and the sympathovagal balance modulating heart rate. These indices might be useful in the future to monitor the fluctuation of sympathetic activity in anesthetized patients.

Relationship between sympathetic activity and pain intensity in fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is a syndrome characterised by chronic musculoskeletal pain, hyperalgesia on specific areas of tenderness (tender points) and by an autonomic nervous system dysfunction consistent with sympathetic overactivity. It is not known whether there is any relationship between the amount of cardiovascular sympathetic activity and the magnitude of pain. Our objective was to assess this potential relationship in patients with FM. METHODS: Electrocardiogram, finger blood pressure, respiration and post-ganglionic sympathetic discharge activity (muscle sympathetic nerve activity, MSNA) were continuously recorded at rest in 25 patients with primary FMS. The autonomic profile was assessed by MSNA and spectral indices of cardiac sympathetic (LFRR) and vagal (HFRR) modulation and of sympathetic vasomotor control (LF-SAP) computed by spectrum analysis of RR and systolic arterial pressure (SAP) variability. Cardiac baroreflex function was evaluated by the index α (αLF). Baroreceptor modulation of the sympathetic vasomotor control (sBRS) was assessed by the MSNA/diastolic pressure relationship. RESULTS: Pain intensity was linearly correlated with LFRR/HFRR (r² = 0.21; p=0.03), LFSAP (r² = 0.26; p=0.02) and MSNA (burst rate) (r² = 0.45; p=0.003). Pain intensity was inversely correlated with the αLF index (r² = 0.24; p=0.02) and the sBRS (r² = 0.28; p=0.03). Thus, the higher the sympathetic drive to the heart and vessels, the higher the magnitude of chronic pain. Also, the gains of both the cardiac and MSNA baroreceptor control were inversely related to the pain intensity. CONCLUSIONS: These findings raise the theoretical possibility that in FM patients the use of anti-adrenergic agents might lessen chronic pain intensity by reducing the underlying excessive sympathetic activity.

Effects of a hydrotherapy programme on symbolic and complexity dynamics of heart rate variability and aerobic capacity in fibromyalgia patients.

OBJECTIVES: To evaluate the effects of a hydrotherapy programme on aerobic capacity and linear and non-linear dynamics of heart rate variability (HRV) in women with fibromyalgia syndrome (FMS). METHODS: 20 women with FMS and 20 healthy controls (HC) took part in the study. The FMS group was evaluated at baseline and after a 16-week hydrotherapy programme. All participants underwent cardiopulmonary exercise testing on a cycle ergometer and RR intervals recording in supine and standing positions. The HRV was analysed by linear and non-linear methods. The current level of pain, the tender points, the pressure pain threshold and the impact of FMS on quality of life were assessed. RESULTS: The FMS patients presented higher cardiac sympathetic modulation, lower vagal modulation and lower complexity of HRV in supine position than the HC. Only the HC decreased the complexity indices of HRV during orthostatic stimulus. After a 16-week hydrotherapy programme, the FMS patients increased aerobic capacity, decreased cardiac sympathetic modulation and increased vagal modulation and complexity dynamics of HRV in supine. The FMS patients also improved their cardiac autonomic adjustments to the orthostatic stimulus. Associations between improvements in non-linear dynamics of HRV and improvements in pain and in the impact of FMS on quality of life were found. CONCLUSIONS: A 16-week hydrotherapy programme proved to be effective in ameliorating symptoms, aerobic functional capacity and cardiac autonomic control in FMS patients. Improvements in the non-linear dynamics of HRV were related to improvements in pain and in the impact of FMS on quality of life.

Acetylcholine-like and trimethylglycine-like PTA (1,3,5-triaza-7-phosphaadamantane) derivatives for the development of innovative Ru- and Pt-based therapeutic agents.

The PTA N-alkyl derivatives (PTAC2H4OCOMe)X (1X: 1a, X = Br; 1b, X = I; 1c, X = PF6; 1d, X = BPh4), (PTACH2COOEt)X (2X: 2a, X = Br; 2b, X = Cl; 2c, X = PF6), and (PTACH2CH2COOEt)X (3X: 3a, X = Br; 3c, X = PF6), presenting all the functional groups of the natural cationic compounds acetylcholine or trimethylglycine combined with a P-donor site suitable for metal ion coordination, were prepared and characterized by NMR, ESI-MS, and elemental analysis. The X-ray crystal structures of 1d and 2c were determined. Ligands 1c, 2b, and 3c were coordinated to Pt(II) and Ru(II) to give the cationic complexes cis-[PtCl2(L)2]X2 and [RuCpCl(PPh3)(L)]X (L = 1, 2, 3, X = Cl or PF6) designed with a structure targeted for anticancer activity. The X-ray crystal structure of [CpRu(PPh3)(PTAC2H4OCOMe)Cl]PF6 (1cRu) was determined. The antiproliferative activity of the ligands and the complexes was evaluated on three human cancer cell lines.

Mitochondrial phylogeny and taxonomic revision of Italian and Slovenian fluvio-lacustrine barbels, Barbus sp. (Cypriniformes, Cyprinidae).

BACKGROUND: Barbels are ray finned cyprinid fishes of the Old-World with partially unresolved, intricate taxonomy. Within the Barbus sensu lato paraphyletic assemblage, Barbus sensu stricto is a monophyletic tetraploid lineage of Europe, northern Africa and Middle East, including two monophyletic sibling genera: Barbus and Luciobarbus. Italy, Slovenia and northern Croatia are natively inhabited by several entities of the genus Barbus, whose relationships and taxonomic ranks are still unclear. Aim of the present work is to focus on phylogeography of Italian and Slovenian barbels, with an appraisal of their current taxonomy. RESULTS: One hundred fifty specimens were collected in 78 sampling sites from 33 main watersheds, widely distributed along Italian and Slovenian ichthyogeographic districts. We amplified two mitochondrial markers, cytochrome b (cytb) and control region (D-loop), to infer a robust phylogeny for our sample and investigate on species delimitation. Our results strongly indicate all Italian and Adriatic Slovenian fluvio-lacustrine barbels to be comprised into at least three distinct species. We provide a proposal of taxonomic revision and a list of synonymies for two of them and a new description under the International Code of Zoological Nomenclature rules for the third one. CONCLUSIONS: If nuclear data will confirm our findings, at least three specific entities should be acknowledged across our sampling area. Namely, the three species are (i) Barbus plebejus, in the Padano-Venetian district; (ii) Barbus tyberinus, in the Tuscany-Latium district; (iii) Barbus oscensis Rossi & Plazzi sp. nov., in the Tyrrhenian and southernmost-Adriatic parts of Apulia-Campania district. Finally, we briefly discuss the implications of such a taxonomic scenario on conservation policies.

Anti-beta-2-glycoprotein I domain 1 identifies antiphospholipid antibodies-related injuries in patients with concomitant lupus nephritis.

BACKGROUND: In this study we aimed to evaluate the usefulness of domain profiling of Beta-2-glycoprotein I(ß2GPI)-Domain-1 (D1) antibodies in relation to antiphospholipid antibodies (aPL)-related nephropathy (aPL-N) in patients with biopsy-proven lupus nephritis (LN). METHODS: Of 124 consecutive patients (96 women, mean age 45.5 ± 12.3 years, mean disease duration 14.7 ± 9.6 years) fulfilling the 1982 criteria for systemic lupus erythematosus (SLE), we identified 39 patients (mean age 39.84 ± 8.6 years, mean disease duration 11.3 ± 7.7 years) with the following characteristics: (a) biopsy-proven LN; (b) no previous diagnosis of antiphospholipid syndrome (APS) according to the current classification criteria. RESULTS: Patients with both LN and aPL-N had higher median aß2GPI-D1 antibody titres (220.1 CU, 25-75th IQ 29.1-334.2) as compared those with LN alone (46.5 CU, 25-75th IQ 12.5-75.1) (p = 0.0087). Median aß2GPI-D1 antibody titres were higher in patients with acute thrombotic microangiopathy (aTMA) (N = 7) (250.1 CU, 25-75th IQ 61.2-334.2) vs. with LN alone (46.5 CU, 25-75th IQ 12.5-75.1 CU) (p = 0.0009). Having a Global Antiphospholipid Syndrome Score > 10 confers an increased probability of having acute features of aTMA (OR 6.25, 95%CI 1.2-31.8). As compared to other aPL, aß2GPI-D1 antibodies have the best diagnostic accuracy for aTMA as evaluated by performances in Area Under the Curves in a ROC analysis. CONCLUSIONS: aß2GPI-D1 antibodies detection might provide a second-line assay to be performed in aß2GPI positive patients with LN, allowing more accurate stratification of the renal vascular involvement risk, thus potentially leading to a more tailored management.

Merkel cell carcinoma of the forehead area: a literature review and case report.

BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon, aggressive malignancy of the skin, mostly affecting head and neck area in elderly white patients. Between head/neck sites, face accounts for 61% and forehead accounts for 17% of all face MCCs. PURPOSE: We here present a literature review MCC cases arising in the forehead area, published in the English literature in the period 1987-2018, and report a personal observation with a late diagnosis and a treatment out of the current recommendations. The aims of this paper are to provide an up-to-date on MCC arising in the forehead area and to raise awareness about misdiagnosis of this type of lesion mimicking arteriovenous malformations (AVM). MATERIAL AND METHOD: Literature review was performed on PubMed and Medline database and "Merkel cell carcinoma (MCC)," "forehead" and "MCC forehead location" were the terms the authors searched for. Patients' data have been drawn from descriptions of single cases and of short case series reports. For each case, data were collected about clinical characteristics, treatment modalities and outcomes. The study has been limited to the clinical features of the disease, excluding etiologic/pathogenic aspects. RESULTS: Twenty-five patients with forehead MCC have been identified, coming from 20 sources. Nineteen presented a locoregional disease and 6 had an advanced pathology. TNM classification was reported in only two cases lacking for the other available data. Patients presented at mean age of 66 years with solitary or multiple nodules or dome-shaped/hemispherical mass, rarely ulcerated. Mean size of tumors was 1.13 cm of max diameter. Previous or concurrent malignancies or immune-hematologic disorders (AIDS) were often associated. At first investigation, lesion was often mistaken for other malignant or benign processes and, then, diagnosis was generally late. Some type of preoperative biopsy was performed in 3 patients, while the others had only a postoperative microscopic study of specimen. Initial treatment consisted in 6 cases (24%) in a not further specified about extent and width of margins local excision of the primary lesion, while a wide resection was reported in only 3 cases (12%). Surgical treatment of involved lymph-nodes was performed in 3 cases (12%). Six patients underwent radiotherapy for locoregional or distant recurrences. Mortality and overall survival rate at five years were 28% and 24%, respectively. Spontaneous regression was observed in 3 patients (12%). CASE REPORT: Personal observation concerned an 82-year-old woman presenting with a forehead periorbital 5 × 5 cm red-bluish mass. The erythematous lesion was erroneously diagnosed as hemangioma on the base of color, the absence of any signs of malignancy, an angio CT indicating a hypervascular tissue and a FNA cytology (FNAC) lacking of malignant cells. The mass was excised as a benign lesion with about 1 cm margins extent without searching larger edges. Postoperative radiotherapy was offered to the patient after histology report, but she refused. After 4 months from surgery, she had a parotid metastasis and died from the illness in spite of platinum-based chemotherapy. CONCLUSIONS: This study confirms the aggressiveness of forehead MCC, comparable with that of other face similar tumors. Personal case suggests that the deceitful benign feature of lesion may mimic an AVM and that FNAC may be misleading and diagnostic failure worsen prognosis. Our experience suggests that in the face smaller than 2-3 cm margins resection may increase the risk of locoregional recurrence. Therefore, postoperative wide-field irradiation should be ever delivered, after forehead MCC surgery, not only when clear margins are unattainable or involved with tumor, but also when negative microscopic edges are documented and residual cancer is thought not persist in the tumor bed. Orbit irradiation seems to be not dangerous for the eye.

Association between autonomic control indexes and mortality in subjects admitted to intensive care unit.

This study checks whether autonomic markers derived from spontaneous fluctuations of heart period (HP) and systolic arterial pressure (SAP) and from their interactions with spontaneous or mechanical respiration (R) are associated with mortality in patients admitted to intensive care unit (ICU). Three-hundred consecutive HP, SAP and R values were recorded during the first day in ICU in 123 patients. Population was divided into survivors (SURVs, n = 83) and non-survivors (NonSURVs, n = 40) according to the outcome. SURVs and NonSURVs were aged- and gender-matched. All subjects underwent modified head-up tilt (MHUT) by tilting the bed back rest segment to 60°. Autonomic control indexes were computed using time-domain, spectral, cross-spectral, complexity, symbolic and causality techniques via univariate, bivariate and conditional approaches. SAP indexes derived from time-domain, model-free complexity and symbolic approaches were associated with the endpoint, while none of HP variability markers was. The association was more powerful during MHUT. Linear cross-spectral and causality indexes were useless to separate SURVs from NonSURVs, while nonlinear bivariate symbolic markers were successful. When indexes were combined with clinical scores, only SAP variance provided complementary information. Cardiovascular control variability indexes, especially when derived after an autonomic challenge such as MHUT, can improve mortality risk stratification in ICU.

Are Nonlinear Model-Free Conditional Entropy Approaches for the Assessment of Cardiac Control Complexity Superior to the Linear Model-Based One?

OBJECTIVE: We test the hypothesis that the linear model-based (MB) approach for the estimation of conditional entropy (CE) can be utilized to assess the complexity of the cardiac control in healthy individuals. METHODS: An MB estimate of CE was tested in an experimental protocol (i.e., the graded head-up tilt) known to produce a gradual decrease of cardiac control complexity as a result of the progressive vagal withdrawal and concomitant sympathetic activation. The MB approach was compared with traditionally exploited nonlinear model-free (MF) techniques such as corrected approximate entropy, sample entropy, corrected CE, two k -nearest-neighbor CE procedures and permutation CE. Electrocardiogram was recorded in 17 healthy subjects at rest in supine position and during head-up tilt with table angles of 15°, 30°, 45°, 60°, and 75°. Heart period (HP) was derived as the temporal distance between two consecutive R-wave peaks and analysis was carried out over stationary sequences of 256 successive HPs. RESULTS: The performance of the MB method in following the progressive decrease of HP complexity with tilt table angles was in line with those of MF approaches and the MB index was remarkably correlated with the MF ones. CONCLUSION: The MB approach can be utilized to monitor the changes of the complexity of the cardiac control, thus speeding up dramatically the CE calculation. SIGNIFICANCE: The remarkable performance of the MB approach challenges the notion, generally assumed in cardiac control complexity analysis based on CE, about the need of MF techniques and could allow real-time applications.

Assessing the strength of cardiac and sympathetic baroreflex controls via transfer entropy during orthostatic challenge.

The study assesses the strength of the causal relation along baroreflex (BR) in humans during an incremental postural challenge soliciting the BR. Both cardiac BR (cBR) and sympathetic BR (sBR) were characterized via BR sequence approaches from spontaneous fluctuations of heart period (HP), systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and muscle sympathetic nerve activity (MSNA). A model-based transfer entropy method was applied to quantify the strength of the coupling from SAP to HP and from DAP to MSNA. The confounding influences of respiration were accounted for. Twelve young healthy subjects (20-36 years, nine females) were sequentially tilted at 0°, 20°, 30° and 40°. We found that (i) the strength of the causal relation along the cBR increases with tilt table inclination, while that along the sBR is unrelated to it; (ii) the strength of the causal coupling is unrelated to the gain of the relation; (iii) transfer entropy indexes are significantly and positively associated with simplified causality indexes derived from BR sequence analysis. The study proves that causality indexes are complementary to traditional characterization of the BR and suggests that simple markers derived from BR sequence analysis might be fruitfully exploited to estimate causality along the BR.This article is part of the themed issue 'Mathematical methods in medicine: neuroscience, cardiology and pathology'.

Effects of laparoscopic radical prostatectomy on intraoperative autonomic nervous system control of hemodynamics.

BACKGROUND: Laparoscopic radical prostatectomy induces hemodynamic changes that have been supposed due to autonomic nervous system activity. The aim of this study is to measure the sympathetic and vagal modulation on hemodynamic response to steep Trendelenburg and pneumoperitoneum for laparoscopic surgery. METHODS: Autonomic nervous system modulation was assessed noninvasively through heart rate variability and arterial pressure variability analysis in patients undergoing elective laparoscopic radical prostatectomy and in awake volunteers during head-down tilt. RESULTS: Forty patients and 14 awake volunteers were studied. The induction of general anesthesia significantly decreased the heart rate, arterial pressure, vagal modulation, and sympathetic modulation. Steep Trendelenburg increased vagal and sympathetic modulation both in anesthetized and awake subjects. Pneumoperitoneum increased arterial pressure without effect on autonomic nervous system control in anesthetized patients. CONCLUSIONS: Hemodynamic changes occurring during laparoscopic radical prostatectomy reveal autonomic response to the challenges (i.e. general anesthesia and head down position), and non-neurally mediated increase of arterial pressure caused by pneumoperitoneum. This study supports the notion that during laparoscopic radical prostatectomy the association between the vagal stimulation due to Trendelenburg positioning and sympathetic withdrawal caused by general anesthesia could lead to severe bradycardia and cardiac arrest in risky patients.

The degree of cardiac baroreflex involvement during active standing is associated with the quality of life in fibromyalgia patients.

Fibromyalgia syndrome (FMS) is a rheumatologic disorder characterized by chronic widespread pain, fatigue and other symptoms. Baroreflex dysfunction has been observed in women with FMS. However, it is unknown whether the limited involvement of the baroreflex control during an orthostatic stimulus has some impact on the quality of life of the FMS patient. Therefore, the aim of the study is evaluate the relationship between the quality of life of the FMS patient and indexes of the cardiovascular autonomic control as estimated from spontaneous fluctuations of heart period (HP) and systolic arterial pressure (SAP). We enrolled 35 women with FMS (age: 48.8±8.9 years; body mass index: 29.3±4.3 Kg/m2). The electrocardiogram, non-invasive finger blood pressure and respiratory activity were continuously recorded during 15 minutes at rest in supine position (REST) and in orthostatic position during active standing (STAND). Traditional cardiovascular autonomic control markers were assessed along with a Granger causality index assessing the strength of the causal relation from SAP to HP (CRSAP→HP) and measuring the degree of involvement of the cardiac baroreflex. The impact of FMS on quality of life was quantified by the fibromyalgia impact questionnaire (FIQ) and visual analog score for pain (VAS pain). No significant linear association was found between FIQ scores and the traditional cardiovascular indexes both at REST and during STAND (p>0.05). However, a negative relationship between CRSAP→HP during STAND and FIQ score was found (r = -0.56, p<0.01). Similar results were found with VAS pain. In conclusion, the lower the degree of cardiac baroreflex involvement during STAND in women with FMS, the higher the impact of FMS on the quality of life, thus suggesting that Granger causality analysis might be clinically helpful in assessing the state of the FMS patient.

Mechanical ventilatory modes and cardioventilatory phase synchronization in acute respiratory failure patients.

Cardioventilatory phase synchronization was studied in ten critically ill patients admitted in intensive care unit (ICU) for acute respiratory failure under two mechanical ventilatory modes: (i) pressure controlled ventilation (PCV); (ii) pressure support ventilation (PSV). The two modalities were administered to the same patient in different times in a random order. Cardioventilatory phase interactions were typified by plotting the relative position of a heartbeat, detected from the electrocardiogram and collected in n groups, within m ventilatory cycles as a function of the progressive cardiac beat number via the synchrogram. n:m phase synchronized patterns were detected by computing the variability of each phase group. The percent duration of the recording featuring phase synchronization was assessed as a measure of the strength of phase synchrony and tested against situations of full phase desynchronization between cardiac and ventilatory rhythms. Indexes quantifying the variability of the cardiac and ventilatory activities were computed as well. Findings proved that: (i) a significant presence of n:m phase synchronized patterns was detected in PCV; (ii) the strength of n:m phase synchronization was stronger during PCV than PSV; (iii) different strengths of cardioventilatory phase synchronization detected during PCV and PSV were found in presence of similar heart and ventilatory rates and alike variability. We conclude that mechanical ventilation can induce a significant presence of cardioventilatory phase synchronized patterns and this amount depends on the mode of mechanical ventilation. Future studies should test the eventual link of the level of phase coordination between heart and mechanical ventilation to a clinical outcome to understand whether featuring a certain degree of cardioventilatory phase synchronization is beneficial for the critical patient in ICU.

Correction: Cardiovascular Variability Analysis and Baroreflex Estimation in Patients with Type 2 Diabetes in Absence of Any Manifest Neuropathy.

[This corrects the article DOI: 10.1371/journal.pone.0148903.].

Nonlinear effects of respiration on the crosstalk between cardiovascular and cerebrovascular control systems.

Cardiovascular and cerebrovascular regulatory systems are vital control mechanisms responsible for guaranteeing homeostasis and are affected by respiration. This work proposes the investigation of cardiovascular and cerebrovascular control systems and the nonlinear influences of respiration on both regulations through joint symbolic analysis (JSA), conditioned or unconditioned on respiration. Interactions between cardiovascular and cerebrovascular regulatory systems were evaluated as well by performing correlation analysis between JSA indexes describing the two control systems. Heart period, systolic and mean arterial pressure, mean cerebral blood flow velocity and respiration were acquired on a beat-to-beat basis in 13 subjects experiencing recurrent syncope episodes (SYNC) and 13 healthy individuals (non-SYNC) in supine resting condition and during head-up tilt test at 60° (TILT). Results showed that JSA distinguished conditions and groups, whereas time domain parameters detected only the effect of TILT. Respiration affected cardiovascular and cerebrovascular regulatory systems in a nonlinear way and was able to modulate the interactions between the two control systems with different outcome in non-SYNC and SYNC groups, thus suggesting that the analysis of the impact of respiration on cardiovascular and cerebrovascular regulatory systems might improve our understanding of the mechanisms underpinning the development of postural-related syncope.