Asthmatic allergen inhalation sensitises carotid bodies to lysophosphatidic acid

The carotid bodies are multimodal sensors that regulate various autonomic reflexes. Recent evidence demonstrates their role in immune reflex regulation. Our previous studies using the allergen (ovalbumin) sensitised and exposed Brown Norway rat model of asthma suggest that carotid bodies mediate asthmatic bronchoconstriction through a lysophosphatidic acid (LPA) receptor (LPAr)-protein kinase C epsilon (PKCε)-transient receptor potential vanilloid one channel (TRPV1) pathway. Whilst naïve carotid bodies respond to LPA, whether their response to LPA is enhanced in asthma is unknown. Here, we show that asthmatic sensitisation of Brown Norway rats involving repeated aerosolised allergen challenges over 6 days, results in an augmentation of the carotid bodies’ acute sensitivity to LPA. Increased expression of LPAr in the carotid bodies and petrosal ganglia likely contributed to this sensitivity. Importantly, allergen sensitisation of the carotid bodies to LPA did not alter their hypoxic response, nor did hypoxia augment LPA sensitivity acutely. Our data demonstrate the ability of allergens to sensitise the carotid bodies, highlighting the likely role of the carotid bodies and blood-borne inflammatory mediators in asthma.

Differences between natural sleep and the anesthetic state

The anesthetic state and natural sleep share many neurobiological features and yet are two distinct states. The hallmarks of general anesthesia include hypnosis, analgesia, akinesia and anxiolysis. These are the principal parameters by which the anesthetic state differs from natural sleep. These properties are mediated by systemic administration of a combination of agents producing balanced anesthesia. The exact nature of anesthetic narcosis is dose dependent and agent specific. It exhibits a relative lack of nociceptive response and active suppression of motor and autonomic reflexes. Surgical anesthesia displays a signature electroencephalogram pattern of burst suppression that differs from rapid eye movement sleep, representing more widespread disruption of thalamocortical connectivity, impairing information integration and processing. These differences underpin successful anesthetic action. This review explores the differences between natural sleep and anesthetic-induced unconsciousness as induced by balanced anesthesia.

Effect of acupuncture on the haemodynamic system in men

Background: Acupuncture stimulation decreases heart rate (HR) through somato-autonomic reflexes. However, the mechanisms responsible for other cardiovascular changes induced by acupuncture, such as its effects on stroke volume (SV) and blood pressure (BP), remain obscure. Objective: To evaluate continuously the comprehensive cardiovascular changes occurring during acupuncture. Method: 20 healthy men participated in the study. HR, SV and BP were measured in the supine position using electrocardiogram, transthoracic impedance cardiography and continuous non-invasive finger blood pressure, respectively. Manual acupuncture stimulation using a stainless steel needle was performed at LI10 for 60 s after resting periods of approximately 15 min. Results: HR was reduced and SV increased, in parallel, during the period of acupuncture stimulation (P<0.01, respectively). Diastolic blood pressure (DBP) decreased in the 10 s period of acupuncture stimulation compared with the 120 s pre-stimulation period (P<0.01) and recovered close to the pre-stimulation reading instantly after the transient reduction. No change was observed in cardiac output (CO) derived from HR and SV. Conclusions: This study indicates that HR reduction during acupuncture does occur, as previous reports have indicated. SV increased during acupuncture stimulation in parallel with HR reduction and CO was maintained during these changes. Any reduction in DBP caused by acupuncture recovered to baseline, likely due to baroreflexes.

A Critique on Baroreceptor and their Effective Reflex Action on Compartmental Cardiovascular Modeling in Regulating Hemodynamic Parameters

Baroreceptor is the feedback unit present in the living beings which acts as a sensor that is located in the walls of blood vessels. This sensor senses the deformation in the blood vessels which causes change in arterial blood pressure and regulates it via Central Nervous System (CNS) and the information are autonomic reflexes that has a great influence on circulatory system elements such as peripheral systemic resistance (Rpsym), contractility of the ventricles (Emax), unstressed volume of the ventricles (Vus_ven) and heart rate (HR). The dynamic behaviour of the baroreceptor is modeled and substantiated by applying the negative feedback mechanism. A detailed modeling and simulation study is presented considering various testing conditions in regulating the circulatory system elements which oversees the Mean Arterial Pressure (MAP) in cardiovascular system. The Total Artificial Cardiovascular model (TAH-CVS) is also developed using pressure, volume and flow related differential equations. Based on the testing conducted under various conditions, the feedback-mechanism of the baroreceptor model is combined with the continuous TAH-CVS closed loop model to validate the effectiveness of the baroreceptor model. The simulation results of TAH-CVS model at initial conditions are compared with the TAH-CVS model with baroreceptor.

Pulmonary arterial hypertension: the case for a bioelectronic treatment

Pulmonary arterial hypertension (PAH) is a rare disease of unknown etiology that progresses to right ventricular failure. It has a complex pathophysiology, which involves an imbalance between vasoconstrictive and vasodilative processes in the pulmonary circulation, pulmonary vasoconstriction, vascular and right ventricular remodeling, systemic inflammation, and autonomic imbalance, with a reduced parasympathetic and increased sympathetic tone. Current pharmacological treatments for PAH include several classes of drugs that target signaling pathways in vascular biology and cardiovascular physiology, but they can have severe unwanted effects and they do not typically stop the progression of the disease. Pulmonary artery denervation has been tested clinically as a method to suppress sympathetic overactivation, however it is a nonspecific and irreversible intervention. Bioelectronic medicine, in particular vagus nerve stimulation (VNS), has been used in cardiovascular disorders like arrhythmias, heart failure and arterial hypertension and could, in principle, be tested as a treatment in PAH. VNS can produce pulmonary vasodilation and renormalize right ventricular function, via activation of pulmonary and cardiac vagal fibers. It can suppress systemic inflammation, via activation of fibers that innervate the spleen. Finally, VNS can gradually restore the balance between parasympathetic and sympathetic tone by regulating autonomic reflexes. Preclinical studies support the feasibility of using VNS in PAH. However, there are challenges with such an approach, arising from the need to affect a relatively small number of relevant vagal fibers, and the potential for unwanted cardiac and noncardiac effects of VNS in this sensitive patient population.

Abstract P393: Orthostatic Heart Rate-Blood Pressure Relationship Identifies Neurogenic Orthostatic Hypotension

Background: Neurogenic orthostatic hypotension (nOH) is a chronic disabling condition associated with significant morbidity and mortality. Currently, the diagnosis of nOH relies on impaired autonomic reflexes as determined by testing available only in specialized centers. Our objective was to test the hypothesis that a blunted heart rate (HR) increase in response to a given systolic blood pressure (SBP) fall will correctly diagnose nOH. Methods: We performed a retrospective study of nOH patients (studied in an inpatient environment off medications that can interfere with autonomic function) and control subjects. nOH was diagnosed on the basis of SBP fall ≥20 mmHg on standing associated with a decrease in SBP≥ 20 mmHg during phase 2 of the Valsalva maneuver and absence of phase 4 SBP overshoot. Controls had any SBP fall on standing but intact autonomic reflexes. Receiver operator characteristic curve (ROC) analysis was performed on the ratio of the changes from supine to 3 min standing in HR and SBP (ΔHR/ΔSBP). Results: We studied 171 nOH patients (66±1 years, males 61%, multiple system atrophy 42%, Parkinson disease 14%, pure autonomic failure 32% and undetermined 12%) and 53 controls (51±3 years, males 28%). nOH patients had a greater drop in standing SBP (-63±2 vs. -16±4 mmHg in controls; p<0.01) but a smaller increase in HR (13±1 vs. 18±1 bpm in controls; p<0.01). The ROC analysis at 95% Confidence Interval showed that a ΔHR/ΔSBP ratio <0.445 had a 81% specificity and 79% sensitivity in identifying nOH (AUC=0.86, p<0.01. Figure). Conclusions: Our study suggests that a simple ratio of ΔSBP/ΔHR <0.445 during a posture test in clinic can reliably identify patients with nOH.