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Neurological disorders, including spinal cord injury, result in hemodynamic instability due to the disruption of supraspinal projections to the sympathetic circuits located in the spinal cord. We recently developed a preclinical model that allows the identification of the topology and dynamics through which sympathetic circuits modulate hemodynamics, supporting the development of a neuroprosthetic baroreflex that precisely controls blood pressure in rats, monkeys and humans with spinal cord injuries. Here, we describe the continuous monitoring of arterial blood pressure and sympathetic nerve activity over several months in preclinical models of chronic neurological disorders using commercially available telemetry technologies, as well as optogenetic and neuronal tract-tracing procedures specifically adapted to the sympathetic circuitry. Using a blueprint to construct a negative-pressure chamber, the approach enables the reproduction, in rats, of well-controlled and reproducible episodes of hypotension-mimicking orthostatic challenges already used in humans. Blood pressure variations can thus be directly induced and linked to the molecular, functional and anatomical properties of specific neurons in the brainstem, spinal cord and ganglia. Each procedure can be completed in under 2 h, while the construction of the negative-pressure chamber requires up to 1 week. With training, individuals with a basic understanding of cardiovascular physiology, engineering or neuroscience can collect longitudinal recordings of hemodynamics and sympathetic nerve activity over several months., (© 2022. Springer Nature Limited.)

Cervical spinal cord injury (SCI) leads to autonomic cardiovascular dysfunction that underlies the three- to fourfold elevated risk of cardiovascular disease in this population. Reduced common carotid artery (CCA) dilatory responsiveness during the cold-pressor test (CPT) is associated with greater cardiovascular disease risk and progression. The cardiovascular and CCA responses to the CPT may provide insight into cardiovascular autonomic dysfunction and cardiovascular disease risk in individuals with cervical SCI. Here, we used CPT to perturb the autonomic nervous system in 14 individuals with cervical SCI and 12 uninjured controls, while measuring cardiovascular responses and CCA diameter. The CCA diameter responses were 55% impaired in those with SCI compared with uninjured controls ( P = 0.019). The CCA flow, velocity, and shear response to CPT were reduced in SCI by 100% ( P < 0.001), 113% ( P = 0.001), and 125% ( P = 0.002), respectively. The association between mean arterial pressure and CCA dilation observed in uninjured individuals ( r = 0.54, P = 0.004) was absent in the SCI group ( r = 0.22, P = 0.217). Steady-state systolic blood pressure ( P = 0.020), heart rate ( P = 0.003), and cardiac contractility ( P < 0.001) were reduced in those with cervical SCI, whereas total peripheral resistance was increased compared with uninjured controls ( P = 0.042). Relative cerebral blood velocity responses to CPT were increased in the SCI group and reduced in controls (middle cerebral artery, P = 0.010; posterior cerebral artery, P = 0.026). The CCA and cardiovascular responsiveness to CPT are impaired in those with cervical SCI. NEW & NOTEWORTHY This is the first study demonstrating that CCA responses during CPT are suppressed in SCI. Specifically, CCA diameter, flow, velocity, and shear rate were reduced. The relationship between changes in MAP and CCA dilatation in response to CPT was absent in individuals with SCI, despite similar cardiovascular activation between SCI and uninjured controls. These findings support the notion of elevated cardiovascular disease risk in SCI and that the cardiovascular responses to environmental stimuli are impaired.

Study Design: Cohort prospective study., Objectives: Epidural spinal cord stimulation (eSCS) improves volitional motor and autonomic function after spinal cord injury (SCI). While eSCS has an established history of safety for chronic pain, it remains unclear if eSCS in the SCI population presents the same risk profile. We aimed to assess safety and autonomic monitoring data for the first 14 participants in the E-STAND trial., Setting: Hennepin County Medical Center, Minneapolis and Minneapolis Veterans Affairs Medical Center, Minnesota, USA., Methods: Monthly follow-up visits assessed surgical and medical device-related safety outcomes as well as stimulation usage. Beat-by-beat blood pressure (BP) and continuous electrocardiogram data were collected during head-up tilt-table testing with and without eSCS., Results: All participants had a motor-complete SCI. Mean (SD) age and time since injury were 38 (10) and 7 (5) years, respectively. There were no surgical complications but one device malfunction 4 months post implantation. Stimulation was applied for up to 23 h/day, across a broad range of parameters: frequency (18-700 Hz), pulse width (100-600 µs), and amplitude (0.4-17 mA), with no adverse events reported. Tilt-table testing with eSCS demonstrated no significant increases in the incidence of elevated systolic BP or a greater frequency of arrhythmias., Conclusions: eSCS to restore autonomic and volitional motor function following SCI has a similar safety profile as when used to treat chronic pain, despite the prevalence of significant comorbidities and the wide variety of stimulation parameters tested., (© 2022. The Author(s), under exclusive licence to International Spinal Cord Society.)

Study Design: Retrospective cross-sectional epidemiological study., Objectives: Previous studies have quantified longitudinal psychological morbidity in individuals with spinal cord injury (SCI) relative to uninjured individuals. However, there is limited information regarding how lifestyle and socioeconomic factors are associated with mental health conditions in individuals with SCI. This study aims to quantify and compare mental health and suicidal thoughts in people with and without SCI, and examine the associations between mental health, suicidal thoughts, sex, age, lifestyle, and socioeconomic factors., Setting: Canada., Methods: The 2010 Canadian Community Health Survey (n > 40,000) was used, which includes several measures assessing mental health and suicidal thoughts. Bivariate and multivariate logistic regressions were performed and odds ratios with corresponding 95% confidence intervals were estimated. Sensitivity analyses were performed to evaluate the effect of covariates on reported effect sizes., Results: People with SCI had higher odds of having mood (3.6) and anxiety disorders (2.5), suicidal thoughts (2.3), self-perceived stress (1.9), and depression (4.4); in addition to lower odds of having good self-perceived mental health (0.24) and satisfaction with life (0.25). These differences persisted after adjusting for age, sex, lifestyle, and socioeconomic factors. Lower household income, fruit and vegetable consumption, and physical activity levels, and increased smoking use were associated with poorer mental health in individuals with SCI., Conclusions: Mental health is poorer in those with SCI when compared with the general population. Those with SCI exhibit a unique profile of lifestyle and socioeconomic factors that are associated with poorer mental health and increased suicidal thoughts., (© 2022. The Author(s), under exclusive licence to International Spinal Cord Society.)

Physical activity is a powerful modifiable risk factor for disease and mortality. Physical activity levels in people with spinal cord injury (SCI) have not been quantified relative to uninjured individuals in a large population-based sample. We aimed to quantify and compare physical activity in people with and without SCI, and to examine the associations between physical activity, lifestyle, and socioeconomic factors. The 2010 Canadian Community Health Survey (n > 57,000) was used, which includes three measures that assess physical activity levels (i.e., leisure time activity frequency, leisure time activity intensity, and transportation time activity intensity). Bivariable and multivariable logistic regressions were performed and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were estimated. The odds of physical activity in people with SCI were 0.43 (95% CI 0.3-0.61), 0.53 (95% CI 0.36-0.75), and 0.42 (95% CI 0.28-0.61), across the three measures of physical activity, respectively. These differences persisted after adjustment for lifestyle, comorbidities, and socioeconomic factors. Physical activity is reduced in the SCI population compared with the general population. This knowledge is important to direct future research and guide the allocation of health care resources., (© 2022. The Author(s).)

Individuals with cervical spinal cord injury (SCI) are at an increased risk for cardiovascular disease. Exercise is well-established for preventing cardiovascular disease; however, there are limited straightforward and safe exercise approaches for increasing the activity of the cardiorespiratory system after cervical SCI. The objective of this study was to investigate the cardiorespiratory response to passive leg cycling in people with cervical SCI. Beat-by-beat blood pressure, heart rate, and cerebral blood flow were measured before and throughout 10 minutes of cycling in 11 people with SCI. Femoral artery flow-mediated dilation was also assessed before and immediately after passive cycling. Safety was monitored throughout all study visits. Passive cycling elevated systolic blood pressure (5 ± 2 mm Hg), mean arterial pressure (5 ± 3 mm Hg), stroke volume (2.4 ± 0.8 mL), heart rate (2 ± 1 beats/min) and cardiac output (0.3 ± 0.07 L/min; all p  < 0.05). Minute ventilation (0.67 ± 0.23 L/min), tidal volume (70 ± 30 mL) and end-tidal PO 2 (2.6 ± 1.23 mm Hg) also increased (all p  < 0.05). Endothelial function was improved immediately after exercise (1.62 ± 0.13%, p  < 0.01). Passive cycling resulted in an incidence of autonomic dysreflexia. Therefore, passive leg cycling increased the activity of the cardiorespiratory system and improved endothelial function, indicating it may be a beneficial exercise intervention for the cardiovascular and respiratory systems in people with cervical SCI. Novelty: Passive leg cycling increases the activity of the cardiorespiratory system and improves markers of cardiovascular health in cervical SCI. Passive leg cycling exercise is an effective, low-cost, practical, alternative exercise modality for people with cervical SCI.

Spinal cord injury (SCI) impairs the cardiovascular responses to postural challenge, leading to the development of orthostatic hypotension (OH). Here, we apply lower body negative pressure (LBNP) to rodents with high-level SCI to demonstrate the usefulness of LBNP as a model for experimental OH studies, and to explore the effect of simulated OH on cardiovascular and cerebrovascular function following SCI. Male Wistar rats ( n = 34) were subjected to a sham or T3-SCI surgery and survived into the chronic period postinjury (i.e., 8 wk). Cardiac function was tracked via ultrasound pre- to post-SCI to demonstrate the clinical utility of our model. At study termination, we conducted left-ventricular (LV) catheterization and insonated the middle cerebral artery to investigate the hemodynamic, cardiac, and cerebrovascular response to a mild dose of LBNP that is sufficient to mimic clinically defined OH in rats with T3-SCI but not sham animals. In response to mimicked OH, there was a greater decline in stroke volume, cardiac output, maximal LV pressure, and blood pressure in SCI compared with sham ( P < 0.034), whereas heart rate was increased in sham but decreased in SCI ( P < 0.029). SCI animals also had an exaggerated reduction in peak, minimum and mean middle cerebral artery flow, for a given change in blood pressure, in response to LBNP ( P < 0.033), implying impaired dynamic cerebral autoregulation. Using a preclinical SCI model of OH, we demonstrate that complete high thoracic SCI impairs the cardiac response to OH and disrupts dynamic cerebral autoregulation. NEW & NOTEWORTHY This is the first use of LBNP to interrogate the cardiac and cerebrovascular responses to simulated OH in a preclinical study of SCI. Here, we demonstrate the utility of our simulated OH model and use it to demonstrate that SCI impairs the cardiac response to simulated OH and disrupts dynamic cerebrovascular autoregulation.

Spinal cord injury (SCI) induces haemodynamic instability that threatens survival 1-3 , impairs neurological recovery 4,5 , increases the risk of cardiovascular disease 6,7 , and reduces quality of life 8,9 . Haemodynamic instability in this context is due to the interruption of supraspinal efferent commands to sympathetic circuits located in the spinal cord 10 , which prevents the natural baroreflex from controlling these circuits to adjust peripheral vascular resistance. Epidural electrical stimulation (EES) of the spinal cord has been shown to compensate for interrupted supraspinal commands to motor circuits below the injury 11 , and restored walking after paralysis 12 . Here, we leveraged these concepts to develop EES protocols that restored haemodynamic stability after SCI. We established a preclinical model that enabled us to dissect the topology and dynamics of the sympathetic circuits, and to understand how EES can engage these circuits. We incorporated these spatial and temporal features into stimulation protocols to conceive a clinical-grade biomimetic haemodynamic regulator that operates in a closed loop. This 'neuroprosthetic baroreflex' controlled haemodynamics for extended periods of time in rodents, non-human primates and humans, after both acute and chronic SCI. We will now conduct clinical trials to turn the neuroprosthetic baroreflex into a commonly available therapy for people with SCI.

New Findings: What is the central question of this study? What is the relative contribution of a putative tonic splenic contraction to the haematological acclimatization process during high altitude ascent in native lowlanders? What is the main finding and its importance? Spleen volume decreased by -14.3% (-15.2 ml) per 1000 m ascent, with an attenuated apnoea-induced [Hb] increase, attesting to a tonic splenic contraction during high altitude ascent. The [Hb]-enhancing function of splenic contraction may contribute to restoring oxygen content early in the acclimatization process at high altitude., Abstract: Voluntary apnoea causes splenic contraction and reductions in heart rate (HR; bradycardia), and subsequent transient increases in haemoglobin concentration ([Hb]). Ascent to high altitude (HA) induces systemic hypoxia and reductions in oxygen saturation ( S p O 2 ), which may cause tonic splenic contraction, which may contribute to haematological acclimatization associated with HA ascent. We measured resting cardiorespiratory variables (HR, S p O 2 , [Hb]) and resting splenic volume (via ultrasound) during incremental ascent from 1400 m (day 0) to 3440 m (day 3), 4240 m (day 7) and 5160 m (day 10) in non-acclimatized native lowlanders during assent to HA in the Nepal Himalaya. In addition, apnoea-induced responses in HR, S p O 2 and splenic volume were measured before and after two separate voluntary maximal apnoeas (A1-A2) at 1400, 3440 and 4240 m. Resting spleen volume decreased -14.3% (-15.2 ml) per 1000 m with ascent, from 140 ± 41 ml (1400 m) to 108 ± 28 ml (3440 m; P > 0.99), 94 ± 22 ml (4240 m; P = 0.009) and 84 ± 28 ml (5160 m; P = 0.029), with concomitant increases in [Hb] from 125 ± 18.3 g l -1 (1400 m) to 128 ± 10.4 g l -1 (3440 m), 138.8 ± 12.7 g l -1 (4240 m) and 157.5 ± 8 g l -1 (5160 m; P = 0.021). Apnoea-induced splenic contraction was 50 ± 15 ml (1400 m), 44 ± 17 ml (3440 m; P > 0.99) and 26 ± 8 ml (4240 m; P = 0.002), but was not consistently associated with increases in [Hb]. The apnoea-induced bradycardia was more pronounced at 3440 m (A1: P = 0.04; A2: P = 0.094) and at 4240 m (A1: P = 0.037 A2: P = 0.006) compared to values at 1400 m. We conclude that hypoxia-induced splenic contraction at rest (a) may contribute to restoring arterial oxygen content through its [Hb]-enhancing contractile function and (b) eliminates further apnoea-induced [Hb] increases in hypoxia. We suggest that tonic splenic contraction may contribute to haematological acclimatization early in HA ascent in humans., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

New Findings: What is the central question of this study? We assessed the utility of a new metric for quantifying ventilatory acclimatization to high altitude, derived from differential ascent and descent steady-state cardiorespiratory variables (i.e. hysteresis). Furthermore, we aimed to investigate whether the magnitude of cardiorespiratory hysteresis was associated with the development of acute mountain sickness. What is the main finding and its importance? Hysteresis in steady-state cardiorespiratory variables quantifies ventilatory acclimatization to high altitude. The magnitude of cardiorespiratory hysteresis during ascent to and descent from high altitude was significantly related to the development of symptoms of acute mountain sickness. Hysteresis in steady-state chemoreflex drive can provide a simple, non-invasive method of tracking ventilatory acclimatization to high altitude., Abstract: Maintenance of arterial blood gases is achieved through sophisticated regulation of ventilation, mediated by central and peripheral chemoreflexes. Respiratory chemoreflexes are important during exposure to high altitude owing to the competing influence of hypoxia and hypoxic hyperventilation-mediated hypocapnia on steady-state ventilatory drive. Inter-individual variability exists in ventilatory acclimatization to high altitude, potentially affecting the development of acute mountain sickness (AMS). We aimed to quantify ventilatory acclimatization to high altitude by comparing differential ascent and descent values (i.e. hysteresis) in steady-state cardiorespiratory variables. We hypothesized that: (i) the hysteresis area formed by cardiorespiratory variables during ascent and descent would quantify the magnitude of ventilatory acclimatization; and (ii) larger hysteresis areas would be associated with lower AMS symptom scores during ascent. In 25 healthy, acetazolamide-free trekkers ascending to and descending from 5160 m, cardiorespiratory hysteresis was measured in the partial pressure of end-tidal CO 2 , peripheral oxygen saturation, minute ventilation, chemoreceptor stimulus index (end-tidal CO 2 /peripheral oxygen saturation) and the calculated steady-state chemoreflex drive (SS-CD; minute ventilation/chemoreceptor stimulus index) using portable devices (capnograph, peripheral pulse oximeter and respirometer, respectively). Symptoms of AMS were assessed daily using the Lake Louise questionnaire. We found that: (i) ascent-descent hysteresis was present in all cardiorespiratory variables; (ii) SS-CD is a valid metric for tracking ventilatory acclimatization to high altitude; and (iii) the highest AMS scores during ascent exhibited a significant, moderate and inverse correlation with the magnitude of SS-CD hysteresis (r s  = -0.408, P = 0.043). We propose that ascent-descent hysteresis is a new and feasible way to quantify ventilatory acclimatization in trekkers during high-altitude exposure., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

Background: High altitude sojourn challenges blood flow regulation in the brain, which may contribute to cognitive dysfunction. Neurovascular coupling (NVC) describes the ability to increase blood flow to working regions of the brain. Effects of high altitude on NVC in frontal regions undergoing cognitive activation are unclear but may be relevant to executive function in high-altitude hypoxia. This study sought to examine the effect of incremental ascent to very high altitude on NVC by measuring anterior cerebral artery (ACA) and middle cerebral artery (MCA) hemodynamic responses to sustained cognitive activity. Materials and Methods: Eight adults (23 ± 7 years, four female) underwent bilateral measurement of ACA and MCA mean velocity and pulsatility index (PI) through transcranial Doppler during a 3-minute Stroop task at 1400, 3440, and 4240 m. Results: Resting MCA and ACA PI decreased with high-altitude hypoxia ( p  < 0.05). Cognitive activity at all altitudes resulted in similar increases in MCA and ACA mean velocity, and decreases in ACA and MCA PI ( p  < 0.05 for MCA, p  = 0.07 for ACA). No significant altitude-by-Stroop interactions were detected, indicating NVC was stable with increasing altitude. Conclusions: Ascent to very high altitude (4240 m) using an incremental profile that supports partial acclimatization does not appear to disturb (1) increases in cerebral blood velocity and (2) reductions in pulsatility that characterize optimal NVC in frontal regions of the brain during cognitive activity.

We wish to find out the quality of the diagnostic test commonly used in epidemiological studies to detect hypertension, and in so doing, we study the validity of epidemiological criteria in the detection of hypertension (diagnostic test) and compare the diagnostic thresholds of the World Health Organization (WHO) and the Joint National Committee (JNC). Two methods of detection for arterial hypertension are used in this study of 674 people. One is population-based (mobile unit), and the other is opportunistic sampling. (systematic measurements of blood pressure in medical consultations). As a test of certainty, clinical confirmation is performed. The methodology of Haynes and Sackett is used in the validation study. The epidemiological criteria obtains a sensibility of 90.4 percent and a specificity of 94.4 percent with the diagnostic thresholds of WHO, and a sensibility of 97 percent and a specificity of 81.2 percent with those of JNC, which are defined as effective methods of screening in the detection of hypertension. The excess prevalence of HBP obtained using the diagnostic criteria of WHO is 4.5 percent (that is to say of 12.2 percent of the cases of hypertension found by the epidemiological criteria, that figure decreases to 7.7% percent with clinical confirmation). With the JNC criteria, it is 14.5 percent (from 34.1 percent, it goes to 19.6 percent). This excess can be used to adjust numbers found in epidemiological studies to their real values.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: It is impossible to evaluate the therapeutic efficacy in hypertension without knowing the compliance of the treatment. The lack of compliance does not allow therapeutic efficacy to be achieved. This study evaluates possible factors involved in the non compliance of treatment in hypertensive patients and the characteristics defining the non compliant patient., Methods: The control technique was tablet counting. The study was carried out in 157 hypertensive patients belonging to the Centro de Carrús (Elche-Alicante, Spain)., Results: 53.3% of the sample were shown to follow the therapy. 45.2% of patients not fulfilling the treatment believed that they were doing it correctly. Non compliance was found to be associated to the following factors: hypertensive patients of older age (p = 0.0054), low cultural level (p = 0.0027), bad knowledge of the disease (p = 0.0166), recent or lengthy knowledge of the disease (p = 0.00677), presence of other associated chronic diseases (p = 0.003), bad control of blood pressure (p = 0.0108), receiving more than two drugs for treatment (p = 0.0071), carrying out more than two medication intakes per day (p = 0.00309), saying that the diet is not well followed (p = 0.0187) and performing other associated pharmacologic treatments (p = 0.0024)., Conclusions: Non compliance is a very frequent fact in patients with hypertension. Knowledge and evaluation of the factors involved in non compliance allows identification and intervention in patients who do not take the medication.

Objective: To find the efficacy of two methods of detecting previously unknown hypertension--systematic taking of blood pressure (ST) and the Mobile Unit (MU)--and to evaluate the over-diagnosis of arterial hypertension (AHT) in crossover studies which only use epidemiological criteria (EC)., Design: A descriptive study with population and opportunist strategies. An operative MU team attended commercial and work centres within the chosen area. ST looked for AHT in patients attending Health Centre clinics., Intervention: EC in screening, in line with WHO guidelines and clinical confirmation (CC) in the Health Centres., Setting: MU in the catchment areas of Novelda, Carrús and C. Jardin Health areas. ST in the San Miguel de Salinas and C. Jardin Health Centres., Patients: 1654 people over 19 with the MU and 4138 through ST., Results: Both methods discovered more hypertension in men (MU p = 0.009 and ST p = 0.000) and in the 20 to 39 age group (MU p = 0.000 and ST p = 0.000). EC led to over-diagnosis (5.8% MU and 6.3% ST); greater in men (6.6% and 6.5%) and +/- 60 years old (8.7% and 7.5%). Positive predictive values obtained were 59.8% with MU and 47.4% with ST., Conclusions: Both methods are useful ways of identifying people suffering hypertension: both young people and men. But CC is essential in order to make a real diagnosis of AHT. Out of every 10 people detected by using EC, only 5 were confirmed by ST and 6 by MU. This information must be borne in mind when evaluating the the prevalence of AHT in epidemiological studies.

Objectives: To validate 4 indirect methods for detecting therapeutic non-compliance in 157 patients in a community health center Centro de Salud "Carrus" in Elche, Alicante., Materials and Methods: The methods employed are self related compliance (SC), therapeutic gains obtained, Morinsky-Green Test, and the level of knowledge of Batalla disease (LK). For verification purposes, pills were counted, allowing the formation of 2x2 tables to calculate indices of validity. The statistical analysis employed is the calculation of 95% confidence intervals., Results: SC yields significantly the lowest sensitivity (13.7 +/- 7.9%) and the highest specificity (85.7% +/- 7.5%). The LK presents the highest sensitivity 79.5 +/- 9.3%. SC underestimates non-compliance (32.5%) significantly, and the LK overestimates noncompliance (23.6%)., Conclusions: The LK is a good method for detecting problems of low compliance and SC those of high compliance. It is recommended that both methods should be employed in a systematic fashion in clinical practice. However, the LK and SC cannot be used to calculate prevalences of therapeutic noncompliance in population-based studies.