Arterial Pressure Variability Research Articles

A New Framework for the Time- and Frequency-Domain Assessment of High-Order Interactions in Networks of Random Processes

While the standard network description of complex systems is based on quantifying the link between pairs of system units, higher-order interactions (HOIs) involving three or more units often play a major role in governing the collective network behavior. This work introduces a new approach to quantify pairwise and HOIs for multivariate rhythmic processes interacting across multiple time scales. We define the so-called O-information rate (OIR) as a new metric to assess HOIs for multivariate time series, and present a framework to decompose the OIR into measures quantifying Granger-causal and instantaneous influences, as well as to expand all measures in the frequency domain. The framework exploits the spectral representation of vector autoregressive and state space models to assess the synergistic and redundant interaction among groups of processes, both in specific bands of interest and in the time domain after whole-band integration. Validation of the framework on simulated networks illustrates how the spectral OIR can highlight redundant and synergistic HOIs emerging at specific frequencies, which cannot be detected using time-domain measures. The applications to physiological networks described by heart period, arterial pressure and respiration variability measured in healthy subjects during a protocol of paced breathing, and to brain networks described by electrocorticographic signals acquired in an animal experiment during anesthesia, document the capability of our approach to identify informational circuits relevant to well-defined cardiovascular oscillations and brain rhythms and related to specific physiological mechanisms involving autonomic control and altered consciousness. The proposed framework allows a hierarchically-organized evaluation of time- and frequency-domain interactions in dynamic networks mapped by multivariate time series, and its high flexibility and scalability make it suitable for the investigation of networks beyond pairwise interactions in neuroscience, physiology and many other fields.

Relationships Between Cardiovascular Autonomic Profile and Work Ability in Patients With Pure Autonomic Failure.

Pure autonomic failure (PAF) is a rare disorder belonging to the group of synucleinopathies, characterized by autonomic nervous system degeneration. Severe orthostatic intolerance with recurrent syncope while standing are the two most disabling manifestations. Symptoms may start at middle age, thus affecting people at their working age. The aims of this study were to evaluate the autonomic and work ability impairment of a group of PAF patients and assess the relationships between cardiovascular autonomic control and work ability in these patients. Eleven PAF patients (age 57.3 ± 6.7 years), engaged in work activity, participated in the study. They completed the Composite Autonomic Symptom Score (COMPASS-31, range 0 no symptom-100 maximum symptom intensity) and Work Ability questionnaires (Work Ability Index, WAI, range 7–49; higher values indicate better work ability and lower values indicating unsatisfactory or jeopardized work ability). Electrocardiogram, blood pressure and respiratory activity were continuously recorded for 10 min while supine and during 75° head-up tilt (HUT). Autoregressive spectral analysis of cardiac cycle length approximated as the time distance between two consecutive R-wave peaks (RR) and systolic arterial pressure (SAP) variabilities provided the power in the high frequency (HF, 0.15–0.40 Hz) and low frequency (LF, 0.04–0.15 Hz) bands of RR and SAP variabilities. Cardiac sympatho-vagal interaction was assessed by LF to HF ratio (LF/HF), while the LF power of SAP (LFSAP) quantified the vascular sympathetic modulation. Changes in cardiovascular autonomic indexes induced by HUT were calculated as the delta (Δ) between HUT and supine resting positions. Spearman correlation analysis was applied. PAF patients were characterized by a moderate autonomic dysfunction (COMPASS-31 total score 47.08 ± 20.2) and by a reduction of work ability (WAI 26.88 ± 10.72). Direct significant correlations were found between WAI and ΔLFRR (r = 0.66, p = 0.03) and ΔLF/HFRR (r = 0.70, p = 0.02). Results indicate that patients who were better able to modulate heart rate, as revealed by a greater cardiac sympathetic increase and/or vagal withdrawal during the orthostatic stimulus, were those who reported higher values of WAI. This finding could be relevant to propose new strategies in the occupational environment to prevent early retirement or to extend the working life of these patients.

Variability of arterial pressure and cardiac rhythm in patients with coronary heart disease and diabetes mellitus: Effect of sodium-glucose co-transporter 2 inhibitor

Introduction: A factor that worsens the course of coronary heart disease (CHD) in patients with type 2 diabetes mellitus (DM2) is cardiovascular autonomic neuropathy (CAN), in which the risk of sudden death increases fivefold. The prevalence of CAN in patients with both CHD and DM2 may reach 60%. Classic cardiovascular tests (CCT) do not permit identification of CAN at the preclinical stage. A modern method of treatment for DM2 uses sodium-glucose co-transporter 2 inhibitors, which have confirmed cardioprotective effects.
 Aim: To analyze the prevalence of alterations of arterial pressure variability (APV) and of heart rhythm variability (HRV) in patients with both CHD and DM2 and the effect of empagliflozin on these parameters.
 Materials and methods: A total of 210 patients aged 64.5 6.7 years (103 men) with both CHD and DM2 were examined (group1). Anthropometric and biochemical parameters were analyzed, electrocardiogram and arterial pressure were monitored daily, and CCT was performed. For comparison, 64 patients with CHD with no alterations in the carbohydrate metabolism were examined (group2, n=64, aged 66.4 2.3 years). Further, among patients in group1, patients with impaired HRV and APV were selected, but they had CCT scores 4.0, and they were divided into group1G (n=22) where empagliflozin was added (1025 mg/day) and group1C (n=20) where the previous therapy was continued.
 Results: CAN was detected in 22% of patients with CHD and DM2, and all patients had impaired HRV and ADV. Deviations of HRV and APV parameters with normal CCT scores ( 4.0) were detected in 43% of the patients. Within 6 months of treatment with empagliflozin, the HbA1c level decreased from 8.38% 0.56% to 6.9% 0.26% (p 0.05); in the groupwithout empagliflozin treatment, it decreased from 8.28% 0.32% to 7.30% 0.29% (p 0.05). In the empagliflozin group, the average heart rate per day decreased from 86.7 2.4 to 76.7 2.1 beats/min (p 0.05), the circadian index increased from 1.19 0.02 to 1.30 0.01 (p 0.05), the SDNN increased from 106.1 2.21 to 114.03 2.34 ms (p 0.05), and the systolic arterial pressure variability index decreased from 22.9% 1.7% to 16.4% 1.9% at daytime (p 0.05) and from 16.8% 2.2% to 12.3% 2.6% at nighttime (p 0.05).
 Conclusion: The identified alterations of HRV and APV parameters may be manifestations of CAN, and CCT score 4.0 may indicate the preclinical stage. Positive dynamics of HRV and APV was recorded with empagliflozin therapy, which improved the functional condition of the autonomic nervous system.

Early arterial pressure monitoring and term-equivalent age MRI findings in very preterm infants.

Variability of arterial blood pressure (ABP) has been associated with intraventricular hemorrhage in very preterm neonates (VPT) and may predict other brain lesions assessed at term-equivalent of age (TEA). This was a prospective single-center study including VPT with early invasive continuous ABP monitoring and assessed at TEA using brain magnetic resonance imaging (TEA-MRI). The association between early mean ABP (MABP) and TEA-MRI findings was modeled by multivariate logistic regression analysis using covariates selected by the LASSO method. Among 99 VPT, the LASSO procedure selected consecutive periods of lowest MABP of 30 min on day 1 (d1) and 10 min on day 2 (d2) as the most relevant durations to predict TEA-MRI findings (OR [95% CI], 1.11 [1.02-1.23], p = 0.03 and 1.13 [1.01-1.27], p = 0.03, respectively). ROC curve analysis showed optimal thresholds at 30.25 mmHg on d1 and 33.25 mmHg on d2. This significant association persisted after adjustment with covariates including birthweight, gestational age, sex, and inotrope exposure. Final models selected by LASSO included the decile of the birthweight and lowest MABP for 30 min on d1 and 10 min on d2, for which the areas under the ROC curve were 74% and 75%, respectively. Early continuous ABP monitoring may predict brain TEA-MRI findings in VPT. Early arterial blood pressure monitoring may contribute to predicting brain damage upon MRI at term-equivalent of age for infants born very preterm. Careful blood pressure continuousmonitoring in very preterm infants may identify infants at risk of long-term brain damage. Umbilical artery catheterization provides the best option for continuously monitoring arterial blood pressure in very preterm infants.

Respiration is a Confounder of the Closed Loop Relationship Between Mean Arterial Pressure and Mean Cerebral Blood Flow.

This study tested the hypothesis that respiration (RESP) is a confounder or suppressor of the closed loop relationship responsible for the cerebrovascular dynamical interactions as assessed from spontaneous variability of mean arterial pressure (MAP) and mean cerebral blood flow (MCBF). The evaluation was carried out in the information domain via transfer entropy (TE) estimated through a linear model-based approach comparing TE markers computed solely over MAP and MCBF series with TE indexes accounting for the eventual action of RESP over MAP and MCBF. We considered 11 patients (age: 76±5 yrs, 7 males) undergoing surgical aortic valve replacement (SAVR) at supine resting (REST) and during active standing (STAND) before and after SAVR surgery. The decrease of the predictive ability of MCBF to MAP when accounting for RESP compared to the one assessed when disregarding RESP suggested that RESP is a confounder of the link from MCBF to MAP along the Cushing reflex instead of being a suppressor. This result was more evident in POST when autonomic control was dramatically depressed and in an unchallenged condition such as REST. RESP did not affect significantly the link from MAP to MCBF along the pressure-to-flow relationship. Clarification of the type of RESP influence on the MAP-MCBF closed loop relationship could favor a deeper characterization of cerebrovascular interactions and the comprehension of cerebral autoregulation mechanisms.Clinical Relevance- This study suggests that respiration is a confounder of the closed loop relationship between MAP and MCBF, especially of the flow-to-pressure causal link. This result might open new possibilities in elucidating the mechanisms of cerebral autoregulation in healthy and pathological populations.

Hemodynamic Responses to Crystalloid and Colloid Fluid Boluses during Noncardiac Surgery.

Colloids are thought to sustain blood pressure and cardiac index better than crystalloids. However, the relative effects of intraoperative hydroxyethyl starch and crystalloid administration on the cardiac index and blood pressure remain unclear. This study therefore tested in this subanalysis of a previously published large randomized trial the hypothesis that intraoperative goal-directed colloid administration increases the cardiac index more than goal-directed crystalloid administration. Further, the effects of crystalloid and colloid boluses on blood pressure were evaluated. This planned subanalysis of a previous trial analyzed data from 973 patients, of whom 480 were randomized to colloids and 493 were randomized to crystalloids. Fluid administration was guided by esophageal Doppler. The primary outcome was the time-weighted average cardiac index during surgery between the colloid and crystalloid group. The secondary outcomes were the cardiac index just after bolus administration, time elapsed between boluses, and the average real variability during surgery. The study recorded cardiac index, corrected flow time, and blood pressure at 10-min intervals, as well as before and after each bolus. Time-weighted average of cardiac index over the duration of anesthesia was only slightly greater in patients given colloid than crystalloid, with the difference being just 0.20 l · min-1 · m-2 (95% CI, 0.11 to 0.29; P < 0.001). However, the hazard for needing additional boluses was lower after colloid administration (hazard ratio [95% CI], 0.60 [0.55 to 0.66]; P < 0.001) in a frailty time-to-event model accounting for within-subject correlation. The median [quartiles] number of boluses per patient was 4 [2, 6] for colloids and 6 [3, 8] for crystalloids, with a median difference (95% CI) of -1.5 (-2 to -1; P < 0.001). The average real mean arterial pressure variability did not differ significantly between the groups (difference in means [95% CI] of -0.03 (-0.07 to 0.02) mmHg, P = 0.229). There were not clinically meaningful differences in the cardiac index or mean pressure variability in patients given goal-directed colloid and crystalloids. As might be expected from longer intravascular dwell time, the interval between boluses was longer with colloids. However, on a case basis, the number of boluses differed only slightly. Colloids do not appear to provide substantial hemodynamic benefit.

Acute autonomic effects of rose oxide on cardiovascular parameters of Wistar and spontaneously hypertensive rats

AimsAnti-inflammatory molecules, such as rose oxide (RO), are likely to exert therapeutic effects in systemic arterial hypertension (SAH), a disease associated with abnormal immune responses. We aimed to investigate acute autonomic effects of RO on hemodynamic parameters of Wistar and spontaneously hypertensive rats (SHR). MethodsRats were anesthetized and femoral artery and veins were cannulated. Next day, blood pressure (BP) and heart rate (HR) were recorded. Acute effects of RO (1.25, 2.5, or 5.0 mg/kg; iv) on BP, HR, and variability of systolic arterial pressure (SAP) and pulse interval (PI) were assessed. The effects of RO were also investigated in SHR, which received atropine (2 mg/kg), propranolol (4 mg/kg), or hexamethonium (20 mg/kg) 15 min before receiving RO. Vasorelaxant effects of RO (10–10 to 10–4 M) on aortic rings of rats were also assessed. Key findingsIn Wistar rats, none of the RO doses evoked significant changes in BP, HR, and variability of SAP and PI. On the other hand, in SHR, RO elicited reduction in mean arterial pressure (MAP), and prevented the increase in the low frequency power (LF) of the SAP spectra. Pretreatment with atropine or propranolol did not alter hypotension, but attenuated RO-induced bradycardia. Hexamethonium prevented RO-induced hypotension and bradycardia. RO exerted vasorelaxant effects on aortic rings with (Wistar and SHR) or without functional endothelium (SHR only). SignificanceRose oxide, a monoterpene with anti-inflammatory properties, acts as an antihypertensive molecule due to its ability to acutely promote hypotension and bradycardia in spontaneously hypertensive rats.

Information decomposition in the frequency domain: a new framework to study cardiovascular and cardiorespiratory oscillations.

While cross-spectral and information-theoretic approaches are widely used for the multivariate analysis of physiological time series, their combined utilization is far less developed in the literature. This study introduces a framework for the spectral decomposition of multivariate information measures, which provides frequency-specific quantifications of the information shared between a target and two source time series and of its expansion into amounts related to how the sources contribute to the target dynamics with unique, redundant and synergistic information. The framework is illustrated in simulations of linearly interacting stochastic processes, showing how it allows us to retrieve amounts of information shared by the processes within specific frequency bands which are otherwise not detectable by time-domain information measures, as well as coupling features which are not detectable by spectral measures. Then, it is applied to the time series of heart period, systolic and diastolic arterial pressure and respiration variability measured in healthy subjects monitored in the resting supine position and during head-up tilt. We show that the spectral measures of unique, redundant and synergistic information shared by these variability series, integrated within specific frequency bands of physiological interest and reflect the mechanisms of short-term regulation of cardiovascular and cardiorespiratory oscillations and their alterations induced by the postural stress. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.

Effects of Algorithmic Music on the Cardiovascular Neural Control.

Music influences many physiological parameters, including some cardiovascular (CV) control indices. The complexity and heterogeneity of musical stimuli, the integrated response within the brain and the limited availability of quantitative methods for non-invasive assessment of the autonomic function are the main reasons for the scarcity of studies about the impact of music on CV control. This study aims to investigate the effects of listening to algorithmic music on the CV regulation of healthy subjects by means of the spectral analysis of heart period, approximated as the time distance between two consecutive R-wave peaks (RR), and systolic arterial pressure (SAP) variability. We studied 10 healthy volunteers (age 39 ± 6 years, 5 females) both while supine (REST) and during passive orthostatism (TILT). Activating and relaxing algorithmic music tracks were used to produce possible contrasting effects. At baseline, the group featured normal indices of CV sympathovagal modulation both at REST and during TILT. Compared to baseline, at REST, listening to both musical stimuli did not affect time and frequency domain markers of both SAP and RR, except for a significant increase in mean RR. A physiological TILT response was maintained while listening to both musical tracks in terms of time and frequency domain markers, compared to baseline, an increase in mean RR was again observed. In healthy subjects featuring a normal CV neural profile at baseline, algorithmic music reduced the heart rate, a potentially favorable effect. The innovative music approach of this study encourages further research, as in the presence of several diseases, such as ischemic heart disease, hypertension, and heart failure, a standardized musical stimulation could play a therapeutic role.

Short-term effect of ligature-induced periodontitis on cardiovascular variability and inflammatory response in spontaneously hypertensive rats

BackgroundWe previously reported that periodontal disease (PD) induces high arterial pressure variability (APV) consistent with sympathetic overactivity and elicits myocardial inflammation in Balb/c mice. However, it is unknown whether PD can change APV and heart rate variability (HRV) in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. This study aimed to evaluate the hemodynamic level, HRV, and APV associating with myocardial inflammation and plasma concentrations of oxide nitric (NO) in SHR and WKY rats with PD.MethodsThree weeks after bilateral ligation of the first mandibular molar, or Sham operation, the rats received catheters into the femoral artery and had their arterial pressure (AP) recorded the following day. Subsequently, plasma, heart, and jaw were collected. The NO was quantified by the chemiluminescence method in plasma, and the myocardial IL-1β concentrations were evaluated by ELISA. In the jaw was evaluated linear alveolar bone loss induced by PD.ResultsThe linear alveolar bone loss in jaws of SHR with PD was higher than in all other groups. AP and heart rate were higher in SHR than in their WKY counterparts. SHR with PD showed lower AP than control SHR. HRV and APV were different between SHR and WKY rats; however, no differences in these parameters were found between the animals with PD and their control counterparts. Plasma NO and myocardial IL-1β concentrations were higher in SHR with PD as compared to control WKY. A significant correlation was found between linear alveolar bone loss and plasma NO and myocardial IL-1β concentrations.ConclusionOur results demonstrated that short-term PD lowered the AP in SHR, which might be due to the higher levels of plasma NO. Even though PD did not affect either HRV or APV, it did induce myocardial inflammation, which can determine cardiovascular dysfunction in long-term PD.

“Impact of Nociception Level (NOL) index intraoperative guidance of fentanyl administration on opioid consumption, postoperative pain scores and recovery in patients undergoing gynecological laparoscopic surgery. A randomized controlled trial”

Study objectiveThe Nociception Level (NOL) index uses a multiparametric approach to measure the balance between sympathetic and parasympathetic systems activity. Recently, a strong correlation between the NOL index response to nociceptive stimuli and the level of opioid analgesia during surgery was reported. Others observed that intraoperative doses of remifentanil and sufentanil were reduced when the NOL index was used. So far, no study has evaluated the impact of NOL-guided fentanyl antinociception in laparoscopic gynecological surgery. The primary hypothesis of this present study was to evaluate whether intraoperative NOL-guided fentanyl administration would reduce intra-operative opioid consumption. Secondary hypotheses were to assess whether this would lead to lower postoperative opioid consumption and pain scores, as well as improved postoperative outcomes. SettingUniversity hospital, operating room. Patients70 adult patients, ASA 1–3, scheduled for total laparoscopic hysterectomy. InterventionsPatients were randomized into 2 groups: SOC (standardization of care) and NOL (using the NOL index to guide the administration of fentanyl). The depth of anesthesia was monitored with BIS™. Intraoperative fentanyl boluses were administered based on heart rate and mean arterial pressure variations in the SOC group, and NOL index for the NOL group. MeasurementsFentanyl total intraoperative dose administered was collected and also averaged per hour. Pain scores and hydromorphone consumption were assessed in the post-anesthesia care unit and up to 24 h. Main resultsSixty-six patients completed the study, 33 in each group. Total intraoperative fentanyl administration was not different between the two groups (217 (70) in the NOL group vs 280 (210) in the SOC group (P = 0.11)). Nevertheless, intraoperative fentanyl administration per hour was reduced by 25% in the NOL-guided group compared to the SOC group: 81 (24) vs 108 (66) μg.h−1, respectively (P = 0.03). Hydromorphone consumption and pain scores in the post-anesthesia care unit and at 24 h were not significantly different between the two groups. ConclusionNOL-guided analgesia allowed for a 22% reduction of the total amount of intraoperative fentanyl which was not significant. Nevertheless, results reported a significant reduction by 25% in the doses of fentanyl averaged per hour of surgery and administered in the NOL-guided group compared with the standardized practice in laparoscopic gynecological surgery. The pain measured postoperatively was similar in the two groups while the average postoperative consumption of opioids to achieve the same level of pain scores in post-anesthesia care unit and at 24 h was not significantly reduced. Further larger multicenter studies centered towards postoperative outcomes are needed.

Changes to intraocular pressure and systemic blood pressure in dogs during moderate treadmill exercise - a short communication

Physical exercise in humans induces changes in intraocular pressure, relating to the type and intensity of the workload. The purpose of the present study was to evaluate the variations in intraocular pressure and arterial blood pressure in dogs that underwent physical exercise on a treadmill. Thirty dogs were submitted to physical exercise consisting of walking (15 minutes), trotting (20 minutes), and walking (10 minutes). The intraocular pressure, blood pressure and pulse rate were recorded for each dog before starting the treadmill exercise, immediately after it ended, and after 20 minutes of passive recovery. Two-way repeated analysis of variance measurement showed the significant effect of treadmill exercise (P≤0.01) on intraocular pressure, pulse rate and diastolic blood pressure. No significant changes were observed to systolic blood pressure. Intraocular pressure and diastolic blood pressure decreased significantly during the passive recovery, and were strongly related. The pulse rate was significantly lower during the passive recovery. Although the mechanism determining the reduction in intraocular pressure during exercise remains not fully understood, our results suggest that it is strongly related to variations in arterial blood pressure.

Abstract MP14: Endothelial Cullin3 Mutation Causes Decreased Nitric Oxide (NO) Bioavailability And Vascular Dysfunction Through Protein Phosphatase 2A

Mutations in CULLIN3 gene (in-frame deletion of exon 9, termed Cul3Δ9) cause human hypertension (HT) driven by a combination of renal tubular and vascular mechanisms. To test the importance of endothelial Cul3 in vivo , we bred the conditionally activatable Cul3Δ9 mice with tamoxifen-inducible Tie2-CRE ERT2 mice. The resultant mice (E-Cul3Δ9) developed arterial stiffening (pulse wave velocity, 3.7±0.3 vs 2.7±0.1 m/s, n=5-7, p&lt;0.05) and a trend towards elevated nighttime blood pressure (peak systolic BP, E-Cul3Δ9 136±3 vs control 128±3 mmHg, n=9-11) that were not associated with any alterations in locomotion, food/water intake or sleep/wake behaviors. No difference was seen in daytime BP. To determine whether vascular remodeling impairs baroreflex function, we performed power spectral analysis. Heart rate (HR), low frequency/high frequency ratio of HR variability, and baroreflex gain were comparable between control and E-Cul3Δ9 mice, suggesting no change in cardiac sympathetic nerve activity. However, low frequency amplitude of arterial pressure variability (16±4 vs 7±2 mmHg 2 , n=5-9, p&lt;0.05) at night was markedly augmented in E-Cul3Δ9 mice, suggesting increased sympathetic activity in vascular tone regulation. Consistently, E-Cul3Δ9 mice exhibited impaired endothelial-dependent relaxation in carotid artery (max ACh relaxation: 69% vs 84%, n=5-7, p&lt;0.05) and cerebral resistance basilar artery (41% vs 77%, n=4-6, p&lt;0.05). However, no dilatory impairment in mesenteric resistance artery and no difference in smooth muscle function were observed, suggesting that the effects of Cul3Δ9 are arterial bed specific. Expression of Cul3Δ9 in primary mouse aortic endothelial cells markedly decreased wild type Cul3 protein, phosphorylated eNOS and NO production. Protein phosphatase (PP) 2A, a known Cul3 substrate, dephosphorylates eNOS. Therefore, we determined whether impaired eNOS activity was attributable to PP2A. Cul3Δ9-induced impairment of eNOS activity was rescued by a selective PP2A inhibitor okadaic acid (4nM), but not by a PP1 inhibitor tautomycetin (4nM). Thus, CUL3 mutations in the endothelium may contribute to human HT in part through decreased endothelial NO bioavailability, arterial stiffening and secondary sympathoexcitation.

Relationship Between Orthostatic Stress Response And Acute Mountain Sickness Susceptibility At High Altitude: Pilot Study

PURPOSE: To determine whether there is a difference in hemodynamic responses to head-up tilt (HUT) in subjects who do, and do not, experience acute mountain sickness (AMS) during exposure to hypobaric hypoxia. We also aimed to determine if those hemodynamic variables altered during HUT correlated with AMS severity. METHODS: Fifteen participants completed three testing sessions: 1) VO2max test to determine workload at 50% VO2max for hypoxia exposure; 2) HUT test consisted of supine rest for 20 min followed by 70° upright tilt for ≤40 min; and 3) six hours of hypobaric hypoxic exposure simulating 4572 m where participants performed two, 30-min cycling bouts and rested when not exercising. During HUT, continuous blood pressure (BP) monitoring was used to assess systolic and diastolic blood pressure (SBP, DBP); mean arterial pressure (MAP); variability in SBP, DBP, and MAP; and heart rate. AMS scores were reported before and after six hours of hypoxic exposure. Statistical analysis included mixed effects ANOVA to determine changes between supine rest and end of HUT and those who scored a ≥ 3 AMS positive (AMS+) and < 3 AMS negative (AMS-) groups. Correlations by linear regression determined associations between HUT hemodynamic responses and AMS scores. Statistical significance was set to p < 0.05. RESULTS: Systolic, diastolic, and mean arterial blood pressure variability (BPV) increased from supine rest to end of HUT (BPV mean difference ± SD for AMS+ & AMS- groups: SBP = 3.5 ± 3.0, 1.2 ± 1.9: DBP = 1.7 ± 1.5, 0.6 ± 0.9: MAP = 2.8 ± 2.9, 1.1 ± 1.4; p = 0.004, 0.004, & 0.006, respectively). Those with higher AMS scores tended to have a greater magnitude of change in SBP, DBP, and MAP variability during the HUT test (r = 0.65, 0.64, & 0.60, respectively). CONCLUSIONS: Increased BPV indicates BP dysregulation, suggesting that AMS+ individuals may have greater disruptions in BP control that could be observable during a postural change prior to hypoxic exposure. BPV during HUT may be a promising predictive variable for AMS but further research is needed. In the future, researchers should consider using sea-level residents and a range of simulated elevations to determine the predictability of AMS susceptibility by BPV.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Variability in Cardiometabolic and Inflammatory Parameters and Cognitive Decline

The relationship between variability in cardiometabolic and inflammatory parameters and cognitive changes is unknown. This study investigates the association of visit-to-visit variability in BMI, mean arterial pressure, total cholesterol, triglycerides, HbA1c, high-sensitivity C-reactive protein, ferritin, and fibrinogen with cognitive decline. This population-based cohort study included 2,260 individuals (mean age=63.0 [SD=7.5] years) free of cognitive diseases who underwent ≥3 clinical measurements from 2004 to 2019. Variability was expressed as variability independent of the mean across visits. Participants were divided on the basis of quartiles of variability score, a scoring system generated to explore the composite effect of parameter variability (range=0-24), where 0 points were assigned for Quartile 1, 1 point was assigned for Quartile 2, 2 points were assigned for Quartile 3, and 3 points were assigned for Quartile 4, each for the variability of 8 parameters measured as variability independent of the mean. Linear mixed models evaluated the longitudinal associations with cognitive decline in memory and verbal fluency. All analyses were conducted in 2020-2021. Higher BMI, mean arterial pressure, total cholesterol, HbA1c, and ferritin variability were linearly associated with cognitive decline irrespective of their mean values. In addition, participants in the highest quartile of variability score had a significantly worse cognitive decline rate in memory (-0.0224 points/year, 95% CI= -0.0319, -0.0129) and verbal fluency (-0.0088 points/year, 95% CI= -0.0168, -0.0008) than those in the lowest quartile. A higher variability in cardiometabolic and inflammatory parameters was significantly associated with cognitive decline. Stabilizing these parameters may serve as a target to preserve cognitive functioning.

Long-Term Visit-to-Visit Mean Arterial Pressure Variability and the Risk of Heart Failure and All-Cause Mortality.

Background: Systolic or diastolic blood pressure (BP) variability is associated with an increased risk of cardiovascular events. We assessed whether BP variability measured by mean arterial pressure (MAP) was associated with increased risk of heart failure (HF) and death in individuals with or without hypertension.Methods: We evaluated 9,305 Atherosclerosis Risk in Communities (ARIC) study participants with or without hypertension and calculated BP variability based on MAP values from visit 1 to 4 [expressed as standard deviation (SD), average real variability (ARV), coefficient of variation (CV), and variability independent of the mean (VIM)]. Multivariate-adjusted Cox regression model and restricted cubic spline curve were used to evaluate the associations of MAP variability with all-cause mortality and HF.Results: During a median follow-up of 16.8 years, 1,511 had an HF event and 2,903 died. Individuals in the highest quartile of VIM were both associated with a 21% higher risk of all-cause mortality [hazard ratio (HR), 1.21; 95% CI, 1.09–1.35] and HF (HR, 1.21; 95% CI, 1.04–1.39) compared with the lowest quartile of VIM. Cubic spline curves reveal that the risk of deaths and HF increased with MAP variability when it reached a higher level. Results were similar in individuals with normotension (all-cause mortality: HR, 1.30; 95% CI, 1.09–1.55; HF, HR, 1.49; 95% CI, 1.12–1.98).Conclusions: In individuals with or without hypertension, greater visit-to-visit MAP variability was associated with a higher risk of all-cause mortality and HF, indicating that the BP variability assessed by MAP might be a potential risk factor for HF and death.

Similar Effects of an Orexin Receptor Antagonistand Benzodiazepine Receptor Agonist on Cerebral Blood Flow Regulation

Orexin receptor antagonists have a different sleep-inducing mechanism from common hypnotic benzodiazepinereceptor agonists. Thus, orexin receptor antagonists may affect cerebral circulation differently, although theireffects have rarely been investigated. In this study, the effects of an orexin receptor antagonist on cerebral bloodflow regulation were compared with those of a benzodiazepine, including dynamic cerebral autoregulation. Fifteenhealthy males received suvorexant (1 tablet, 20 mg), an orexin receptor antagonist, and brotizolam (1 tablet, 0.25mg), a benzodiazepine receptor agonist, in a randomized order at least 7 days apart. Before and 1.5 h after drugadministration, arterial blood pressure and cerebral blood flow velocity were measured by transcranial Doppler ina supine position. Dynamic cerebral autoregulation was evaluated by transfer function analysis between mean arterial blood pressure variability and mean cerebral blood flow velocity variability. The steady-state mean cerebralblood flow velocity decreased significantly with both suvorexant and brotizolam (significant main effect of time,P = 0.003) and was associated with unchanged steady-state mean arterial blood pressure. Moreover, transfer function gain in the low- and high-frequency ranges were decreased significantly by both suvorexant and brotizolam(significant main effect of time, P < 0.001), suggesting a decrease in the magnitude of transfer from arterial bloodpressure oscillations to cerebral blood flow fluctuations. These changes were not significantly different betweensuvorexant and brotizolam (no significant interaction effect). The present results indicate that suvorexant andbrotizolam, two different types of hypnotic drug, have similar effects on cerebral blood flow regulation, includingpossible improvements in dynamic cerebral autoregulation with decreased steady-state cerebral blood flow.

Autonomic biomarkers of shock in idiopathic systemic capillary leak syndrome.

ObjectiveThe term Idiopathic Systemic Capillary Leak Syndrome (ISCLS) refers to an uncommon condition of severe distributive shock, resulting from an abrupt shift of fluids and proteins from the intravascular to the interstitial compartment. We hypothesise that the autonomic nervous system (ANS) fails in regulating the response to hypovolemia in acute ISCLS and that ANS variables characterise the progression to the recovery.DesignProspective cohort study of patients admitted to ICU for severe ISCLS flares.SettingSingle, referral center in Italy for ISCLS.PatientsAnalysis of cardiovascular signals recorded during seven severe ISCLS attacks and one prodromal period in five patients.InterventionsANS was studied non-invasively by means of heart rate variability (HRV) and blood pressure variability analysis, as an estimation of vagal and sympathetic modulation directed to the heart and vessels. Heart rate and systolic arterial pressure (SAP) variability were also used to assess baroreflex sensitivity. ANS variables were measured during the subsequent phases which characterise ISCLS flares, namely the acute phase, the post-acute phase, and the recovery phase.Measurements and main resultsHRV was severely depressed during the acute phase accounting for the loss of ANS modulation during massive capillary extravasation. This phase was characterised by shock and impaired baroreflex control, which allowed SAP to oscillate driven by respiratory activity. Impending shock and transition from shock to a post-acute phase were marked by change of baroreflex spectral variables. The baroreflex control was fully restored during recovery.ConclusionsANS modulation and baroreflex control are severely impaired during the acute haemodynamic instability which characterises ISCLS crises and their progressive restoration may be a clue of improvement. ANS indices during ISCLS flares might serve as useful biomarkers, able to timely announce the transition from one phase to the subsequent one, thus helping to adapt therapy accordingly.

Comparison of frequency domain measures based on spectral decomposition for spontaneous baroreflex sensitivity assessment after Acute Myocardial Infarction

The objective of this study is to present a new method to assess in the frequency domain the directed interactions between the spontaneous variability of systolic arterial pressure (SAP) and heart period (HP) from their linear model representation, and to apply it for studying the baroreflex control of arterial pressure in healthy physiological states and after acute myocardial infarction (AMI). The method is based on pole decomposition of the model transfer function and on the following evaluation of causal measures of coupling and gain from the poles associated to low frequency (0.04−0.15 Hz) oscillatory components. It is compared with traditional non-causal approaches for the spectral analysis of the baroreflex gain, and with causal approaches based on the directed coherence, in a group of AMI patients and in Young and Old healthy controls studied at rest and during head-up tilt. Analysis of feedforward interactions from RR to SAP is also performed. Our results support the importance of using local causal approaches to quantify separately baroreflex and feedforward interactions between RR and SAP, allowing both to confirm known physiological behaviors (e.g., weaker baroreflex effectiveness and lower sensitivity after AMI) and to suggest novel findings (e.g., preserved low frequency baroreflex response to postural stress after AMI). We also find that the postural stress alters feedforward interactions selectively across groups, being related to decreased coupling only in Young and to increased gain mostly in AMI. These results have a significance for the clinical assessment of the baroreflex and the physiological evaluation of cardiovascular interactions.