Vagal nerve stimulation therapy: what is being stimulated?

Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity

Vagal Nerve Stimulation Therapy: What Is Being Stimulated?

Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity

Cardiac Baroreflex Variability and Resetting during Sustained Mild Effort

This exploratory study assessed the pattern of closed-loop baroreflex resetting using multi-logistic-curve analysis. Operating point gain and ranges of RR-interval (RRI) and systolic blood pressure (SBP) are derived to examine how these relate to sympathetic activation. Sustained low-intensity isometric handgrip exercise, with a period of post-exercise circulatory occlusion (PECO), provided a model to study baroreflex resetting because the progression toward fatigue at constant tension induces a continuous increase in volitional contribution to neuro-cardiovascular control. Continuous measurements of muscle sympathetic nerve activity (MSNA), blood pressure, and RRI were made simultaneously throughout the experimental session. Spontaneous sequence analysis was used to detect episodes of baroreflex “engagements”, but the results are examined with a view to the fundamental difference between experimental conditions that isolate the carotid sinus (open-loop) and intact physiological conditions (closed-loop). While baroreflex function under open-loop conditions can be described in terms of a single logistic curve, intact physiologic conditions require a family of logistic curves. The results suggest that the baroreflex is in a “floating” state whereby it is continuously resetting during the timeline of the experiment but with minute-by-minute average values that mimic the less complex step-wise resetting pattern reported under open-loop conditions. Furthermore, the results indicate that baroreflex function and resetting of the operating point gain is reflected not in terms of change in the values of blood pressure or RR-interval but in terms of change in the range of values of these variables prevailing under different experimental conditions

Cerebrovascular compliance within the rigid confines of the skull

© 2018 Zamir, Moir, Klassen, Balestrini and Shoemaker. Pulsatile blood flow is generally mediated by the compliance of blood vessels whereby they distend locally and momentarily to accommodate the passage of the pressure wave. This freedom of the blood vessels to exercise their compliance may be suppressed within the confines of the rigid skull. The effect of this on the mechanics of pulsatile blood flow within the cerebral circulation is not known, and the situation is compounded by experimental access difficulties. We present an approach which we have developed to overcome these difficulties in a study of the mechanics of pulsatile cerebral blood flow. The main finding is that while the innate compliance of cerebral vessels is indeed suppressed within the confines of the skull, this is compensated somewhat by compliance provided by other extravascular elements within the skull. The net result is what we have termed intracranial compliance, which we argue is more pertinent to the mechanics of pulsatile cerebral blood flow than is intracranial pressure

Regulation of cerebrovascular compliance compared with forearm vascular compliance in humans:a pharmacological study

Increasing evidence indicates that cerebrovascular compliance contributes to the dynamic regulation of cerebral blood flow but the mechanisms regulating cerebrovascular compliance in humans are unknown. This retrospective study investigated the impact of neural, endothelial, and myogenic mechanisms on the regulation of vascular compliance in the cerebral vascular bed compared with the forearm vascular bed. An index of vascular compliance (C(i)) was assessed using a Windkessel model applied to blood pressure waveforms (finger photoplethysmography) and corresponding middle cerebral artery blood velocity or brachial artery blood velocity waveforms (Doppler ultrasound). Data were analyzed during a 5-min baseline period (10 waveforms) under control conditions and during distinct sympathetic blockade (experiment 1, phentolamine; 10 adults), cholinergic blockade (experiment 2, glycopyrrolate; 9 adults), and myogenic blockade (experiment 3, nicardipine; 14 adults). In experiment 1, phentolamine increased C(i) similarly in the cerebral vascular bed (131 ± 135%) and forearm vascular bed (93 ± 75%; P = 0.45). In experiment 2, glycopyrrolate increased cerebrovascular C(i) (72 ± 61%) and forearm vascular C(i) (74 ± 64%) to a similar extent (P = 0.88). In experiment 3, nicardipine increased C(i) but to a greater extent in the cerebral vascular bed (88 ± 88%) than forearm vascular bed (20 ± 45%; P = 0.01). Therefore, adrenergic, cholinergic, and myogenic mechanisms contribute to the regulation of cerebrovascular and forearm vascular compliance. However, myogenic mechanisms appear to exert more specific control over vascular compliance in the brain relative to the forearm. NEW & NOTEWORTHY Vascular compliance represents an important determinant in the dynamics and regulation of blood flow through a vascular bed. However, the mechanisms that regulate vascular compliance remain poorly understood. This study examined the impact of neural, endothelial, and myogenic mechanisms on cerebrovascular compliance compared with forearm vascular compliance. Distinct pharmacological blockade of α-adrenergic, endothelial muscarinic, and myogenic inputs altered cerebrovascular and forearm vascular compliance. These results further our understanding of vascular control and blood flow regulation in the brain

Effects of acute and chronic interval sprint exercise performed on a manually propelled treadmill on upper limb vascular mechanics in healthy young men

© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. Interval sprint exercise performed on a manually propelled treadmill, where the hands grip the handle bars, engages lower and upper limb skeletal muscle, but little is known regarding the effects of this exercise modality on the upper limb vasculature. We tested the hypotheses that an acute bout of sprint exercise and 6 weeks of training induces brachial artery (BA) and forearm vascular remodeling, favoring a more compliant system. Before and following a single bout of exercise as well as 6 weeks of training three types of vascular properties/methodologies were examined in healthy men: (1) stiffness of the entire upper limb vascular system (pulse wave velocity (PWV); (2) local stiffness of the BA; and (3) properties of the entire forearm vascular bed (determined by a modified lumped parameter Windkessel model). Following sprint exercise, PWV declined (P \u3c 0.01), indices of BA stiffness did not change (P ≥ 0.10), and forearm vascular bed compliance increased and inertance and viscoelasticity decreased (P ≤ 0.03). Following manually propelled treadmill training, PWV remained unchanged (P = 0.31), indices of BA stiffness increased (P ≤ 0.05) and forearm vascular bed viscoelasticity declined (P = 0.02), but resistance, compliance, and inertance remained unchanged (P ≥ 0.10) compared with pretraining values. Sprint exercise induced a more compliant forearm vascular bed, without altering indices of BA stiffness. These effects were transient, as following training the forearm vascular bed was not more compliant and indices of BA stiffness increased. On the basis of these data, we conclude that adaptations to acute and chronic sprint exercise on a manually propelled treadmill are not uniform along the arterial tree in upper limb

Video-calls to reduce loneliness and social isolation within care environments for older people: an implementation study using collaborative action research

Background  Older people in care may be lonely with insufficient contact if families are unable to visit. Face-to-face contact through video-calls may help reduce loneliness, but little is known about the processes of engaging people in care environments in using video-calls. We aimed to identify the barriers to and facilitators of implementing video-calls for older people in care environments.  Methods  A collaborative action research (CAR) approach was taken to implement a video-call intervention in care environments. We undertook five steps of recruitment, planning, implementation, reflection and re-evaluation, in seven care homes and one hospital in the UK. The video-call intervention ‘Skype on Wheels’ (SoW) comprised a wheeled device that could hold an iPad and handset, and used Skype to provide a free video-call service. Care staff were collaborators who implemented the intervention within the care-setting by agreeing the intervention, recruiting older people and their family, and setting up video-calls. Field notes and reflective diaries on observations and conversations with staff, older people and family were maintained over 15 months, and analysed using thematic analysis.  Results  Four care homes implemented the intervention. Eight older people with their respective social contacts made use of video-calls. Older people were able to use SoW with assistance from staff, and enjoyed the use of video-calls to stay better connected with family. However five barriers towards implementation included staff turnover, risk averseness, the SoW design, lack of family commitment and staff attitudes regarding technology.  Conclusions  The SoW intervention, or something similar, could aid older people to stay better connected with their families in care environments, but if implemented as part of a rigorous evaluation, then co-production of the intervention at each recruitment site may be needed to overcome barriers and maximise engagement

Home and Online Management and Evaluation of Blood Pressure (HOME BP) using a digital intervention in poorly controlled hypertension: randomised controlled trial

Objective: The HOME BP (Home and Online Management and Evaluation of Blood Pressure) trial aimed to test a digital intervention for hypertension management in primary care by combining self-monitoring of blood pressure with guided self-management. Design: Unmasked randomised controlled trial with automated ascertainment of primary endpoint. Setting: 76 general practices in the United Kingdom. Participants: 622 people with treated but poorly controlled hypertension (>140/90 mm Hg) and access to the internet. Interventions: Participants were randomised by using a minimisation algorithm to self-monitoring of blood pressure with a digital intervention (305 participants) or usual care (routine hypertension care, with appointments and drug changes made at the discretion of the general practitioner; 317 participants). The digital intervention provided feedback of blood pressure results to patients and professionals with optional lifestyle advice and motivational support. Target blood pressure for hypertension, diabetes, and people aged 80 or older followed UK national guidelines. Main outcome measures: The primary outcome was the difference in systolic blood pressure (mean of second and third readings) after one year, adjusted for baseline blood pressure, blood pressure target, age, and practice, with multiple imputation for missing values. Results: After one year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean blood pressure dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic blood pressure of −3.4 mm Hg (95% confidence interval −6.1 to −0.8 mm Hg) and a mean difference in diastolic blood pressure of −0.5 mm Hg (−1.9 to 0.9 mm Hg). Results were comparable in the complete case analysis and adverse effects were similar between groups. Within trial costs showed an incremental cost effectiveness ratio of £11 ($15, €12; 95% confidence interval £6 to £29) per mm Hg reduction. Conclusions: The HOME BP digital intervention for the management of hypertension by using self-monitored blood pressure led to better control of systolic blood pressure after one year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded. Trial registration: ISRCTN13790648