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CNS Neuroscience & Therapeutics Mar 2022To understand the direct impact of bradykinin in autonomic control of circulation through baroreflex afferent pathway.
AIM
To understand the direct impact of bradykinin in autonomic control of circulation through baroreflex afferent pathway.
METHODS
The mean arterial pressure (MAP) was monitored while bradykinin and its agonists were applied via nodose (NG) microinjection, the expression of bradykinin receptors (BRs) in the NG (1 -order) and nucleus tractus solitarius (NTS, 2 -order) were tested in adult male, age-matched female, and ovariectomized rats under physiological and hypertensive conditions. Additionally, bradykinin-induced depolarization was also tested in identified baroreceptor and baroreceptive neurons using whole-cell patch-clamp technique.
RESULTS
Under physiological condition, bradykinin-induced dose- and estrogen-dependent reductions of MAP with lower estimated EC in females. B R agonist mediated more dramatic MAP reduction with long-lasting effect compared with B R activation. These functional observations were consistent with the molecular and immunostaining evidences. However, under hypertensive condition, the MAP reduction was significantly less dramatic in N -Nitro-L-Arginine-methyl ester (L-NAME) induced secondary and spontaneous hypertension rats in males compared with female rats. Electrophysiological data showed that bradykinin-elicited concentration-dependent membrane depolarization with discharges during initial phase in identified myelinated Ah-types baroreceptor neurons, not myelinated A-types; while, higher concentration of bradykinin was required for depolarization of unmyelinated C-types without initial discharges.
CONCLUSION
These datasets have demonstrated for the first time that bradykinin mediates direct activation of baroreflex afferent function to trigger estrogen-dependent depressor response, which is due mainly to the direct activation/neuroexcitation of female-specific myelinated Ah-type baroreceptor neurons leading to a sexual dimorphism in parasympathetic domination of blood pressure regulation via activation of B R/B R expression in baroreflex afferent pathway.
Topics: Animals; Baroreflex; Bradykinin; Estrogens; Female; Hypertension; Male; Neurons; Pressoreceptors; Rats; Rats, Inbred SHR
PubMed: 34964272
DOI: 10.1111/cns.13792 -
Cardiology in Review 2021There has been significant interest in research for the development of device-based therapy as a treatment option of heart failure (HF), whether it is with reduced or... (Review)
Review
There has been significant interest in research for the development of device-based therapy as a treatment option of heart failure (HF), whether it is with reduced or preserved ejection fraction. This is due to the high morbidity and mortality rate in patients with HF despite recent advances in pharmacologic treatment. Following the success of cardiac resynchronization therapy, baroreceptor activation therapy has emerged as another novel device-based treatment for HF. The Barostim neo was developed by CVRx Minneapolis, MN for the treatment of mild to severe HF. The device works by electrically activating the baroreceptor reflex with the goal to restore the maladaptive autonomic imbalance that is seen in patients with HF. Preliminary clinical investigations have given promising results with an encouraging safety profile. Baroreceptor activation therapy as a treatment option is still investigational at this time; however, several trials in different patient populations have already shown benefit with a very good safety profile. In this review, we will summarize the current state of technology and the available literature of the use of baroreceptor activation therapy in patients with different comorbidities, with a focus on this device-based therapy in patients with HF.
Topics: Baroreflex; Cardiac Resynchronization Therapy; Heart Failure; Humans; Pressoreceptors; Prostheses and Implants
PubMed: 32282391
DOI: 10.1097/CRD.0000000000000307 -
The Journal of Maternal-fetal &... Dec 2023Baroreflex is a regulatory mechanism that slows the fetal heart rate. This study aimed to investigate the effects of lipopolysaccharide (LPS)-induced endotoxemia on...
OBJECTIVE
Baroreflex is a regulatory mechanism that slows the fetal heart rate. This study aimed to investigate the effects of lipopolysaccharide (LPS)-induced endotoxemia on fetal baroreceptor sensitivity in preterm fetal sheep.
METHODS
The changes in fetal baroreceptor sensitivity were measured in seven chronically instrumented preterm fetal sheep. Fetal baroreceptor sensitivity was measured in three phases: (A) control phase, defined as the 24 h before the first injection of LPS; (B) acute phase, defined as the 24 h between the first and second injections of LPS; and (C) fetal acidosis phase, defined as the time from the second LPS injection until intrauterine fetal death. Histological examinations of the fetal membrane and umbilical cord were also conducted.
RESULTS
Each fetus developed metabolic acidosis after the second injection of LPS. The fetuses died 24.7 (SD = 6.1) hours after the second injection of LPS. Both the umbilical cord and fetal membranes showed histological evidence of severe inflammation. In total, 163 fetal baroreceptor measurements were performed in this experiment (A, = 77 times; B, = 60 times; C, = 26 times). Fetal baroreceptor sensitivity showed significant differences in all three phases (A: 2.7 [SD = 0.2]; B: 2.5 [SD = 0.2]; and C: 1.5 [SD = 0.2]). Post hoc tests showed that baroreceptor sensitivity in the acidosis phase had decreased significantly compared to that in the control and acute phases (<.001 and =.002, respectively).
CONCLUSIONS
Fetal baroreceptor sensitivity decreased during fetal acidosis induced by LPSs.
Topics: Pregnancy; Female; Humans; Sheep; Animals; Lipopolysaccharides; Pressoreceptors; Fetus; Inflammation; Fetal Diseases; Acidosis; Heart Rate, Fetal
PubMed: 36443245
DOI: 10.1080/14767058.2022.2150392 -
Journal of Atherosclerosis and... Apr 2024The carotid sinuses and aortic arch are baroreceptor-resident arteries (BRAs) and atherosclerosis-susceptible sites of brain-supplying arteries, which would impair...
Evaluating Total Atherosclerosis Burden of Baroreceptor-Resident Arteries after Ischemic Cerebrovascular Disease for Identifying Patients with Heavy Coronary Atherosclerosis Burden.
AIM
The carotid sinuses and aortic arch are baroreceptor-resident arteries (BRAs) and atherosclerosis-susceptible sites of brain-supplying arteries, which would impair baroreflex-mediated blood pressure (BP) regulation and prompt coronary atherosclerosis. We sought to determine the relationship between total atherosclerosis burden (TAB) of BRAs and coronary atherosclerosis burden (AB) in patients with ischemic cerebrovascular disease (ICVD) and explore the potential contribution of BP profiles to this relationship.
METHODS
In this cross-sectional analysis of patients with ICVD who simultaneously undertook computed tomography angiography and 24-hour ambulatory BP monitoring, TAB of BRAs was scored based on the atherosclerotic vessel circumference ratio of the carotid sinuses and aortic arch, while the ABs of the intracranial, cervical, aortic, and coronary arteries were scored based on stenosis severity and plaque complexity as routine.
RESULTS
Among the 230 patients analyzed, coronary AB was significantly correlated with TAB of BRAs, independently of, and more tightly than the ABs of the intracranial, cervical, and aortic arteries, and the stenosis- and complexity-based AB of BRA-located arteries (bilateral common and extracranial internal carotid arteries and aortic arch). Both coronary AB and TAB of BRAs were negatively associated with the night-to-day BP dipping ratios, which was quite different from the relationship between intracranial AB and 24-hour BP characteristics. These findings were also true for patients with ICVD without a history of coronary artery disease.
CONCLUSION
Evaluating TAB of BRAs might provide a new link between atherosclerosis of brain- and heart-supplying arteries, connected partially by BP circadian rhythm. It might facilitate identifying patients with ICVD with heavy coronary AB and comprehensively managing vascular risk.
Topics: Humans; Coronary Artery Disease; Stroke; Constriction, Pathologic; Pressoreceptors; Cross-Sectional Studies; Risk Factors; Atherosclerosis; Arteries
PubMed: 37866928
DOI: 10.5551/jat.64457 -
Pediatric Cardiology Jun 2022The arterial baroreceptor reflex in children and adolescents has not been well studied in the current literature with a lack of agreed upon normal values, particularly...
The arterial baroreceptor reflex in children and adolescents has not been well studied in the current literature with a lack of agreed upon normal values, particularly in postural orthostatic tachycardia syndrome (POTS) or neurocardiogenic syncope (NCS). We used the sequence method and head-up tilt test (HUTT) to evaluate baroreceptor function in 3 phases: baseline supine position for 10 min, head-up position at 70° for 30 min or until syncope, and post-tilt supine reposition for 10 min. We measured the number of baroreceptor events, baroreceptor effectiveness index (BEI), and the magnitude of sensitivity of the events at each phase of HUTT. We studied 198 individuals (49 normal subjects, 67 POTS, 82 NCS) with age ranges from 8 to 21 years. The data show a statistically significant decrease in slope and BEI in patients with POTS and NCS during the head-up phase, with an increase in activity in the lag 1 and 2 portions of all phases in patients with POTS. This study provides terminology to describe baroreceptor function and identifies the slope and BEI portions of the baroreceptor reflex as the most useful objective measures to differentiate pediatric patients with POTS and NCS from normal subjects.
Topics: Adolescent; Adult; Blood Pressure; Child; Heart Rate; Humans; Postural Orthostatic Tachycardia Syndrome; Pressoreceptors; Syncope, Vasovagal; Tachycardia; Tilt-Table Test; Young Adult
PubMed: 35089394
DOI: 10.1007/s00246-022-02815-1 -
BMC Cardiovascular Disorders Sep 2019Remote ischemic conditioning (RIC) is a procedure applied in a limb for triggering endogenous protective pathways in distant organs, namely brain or heart. The...
BACKGROUND
Remote ischemic conditioning (RIC) is a procedure applied in a limb for triggering endogenous protective pathways in distant organs, namely brain or heart. The underlying mechanisms of RIC are still not fully understood, and it is hypothesized they are mediated either by humoral factors, immune cells and/or the autonomic nervous system. Herein, heart rate variability (HRV) was used to evaluate the electrophysiological processes occurring in the heart during RIC and, in turn to assess the role of autonomic nervous system.
METHODS
Healthy subjects were submitted to RIC protocol and electrocardiography (ECG) was used to evaluate HRV, by assessing the variability of time intervals between two consecutive heart beats. This is a pilot study based on the analysis of 18 ECG from healthy subjects submitted to RIC. HRV was characterized in three domains (time, frequency and non-linear features) that can be correlated with the autonomic nervous system function.
RESULTS
RIC procedure increased significantly the non-linear parameter SD2, which is associated with long term HRV. This effect was observed in all subjects and in the senior (> 60 years-old) subset analysis. SD2 increase suggests an activation of both parasympathetic and sympathetic nervous system, namely via fast vagal response (parasympathetic) and the slow sympathetic response to the baroreceptors stimulation.
CONCLUSIONS
RIC procedure modulates both parasympathetic and sympathetic autonomic nervous system. Furthermore, this modulation is more pronounced in the senior subset of subjects. Therefore, the autonomic nervous system regulation could be one of the mechanisms for RIC therapeutic effectiveness.
Topics: Adult; Aged; Autonomic Nervous System; Baroreflex; Electrocardiography; Female; Healthy Volunteers; Heart; Heart Rate; Humans; Ischemic Preconditioning; Male; Middle Aged; Pilot Projects; Pressoreceptors; Regional Blood Flow; Time Factors; Upper Extremity
PubMed: 31500561
DOI: 10.1186/s12872-019-1181-5 -
Circulation. Heart Failure Jan 2021Continuous-flow (CF) left ventricular assist devices (LVADs) improve outcomes for patients with advanced heart failure (HF). However, the lack of a physiological pulse...
Impairments in Blood Pressure Regulation and Cardiac Baroreceptor Sensitivity Among Patients With Heart Failure Supported With Continuous-Flow Left Ventricular Assist Devices.
BACKGROUND
Continuous-flow (CF) left ventricular assist devices (LVADs) improve outcomes for patients with advanced heart failure (HF). However, the lack of a physiological pulse predisposes to side-effects including uncontrolled blood pressure (BP), and there are little data regarding the impact of CF-LVADs on BP regulation.
METHODS
Twelve patients (10 males, 60±11 years) with advanced heart failure completed hemodynamic assessment 2.7±4.1 months before, and 4.3±1.3 months following CF-LVAD implantation. Heart rate and systolic BP via arterial catheterization were monitored during Valsalva maneuver, spontaneous breathing, and a 0.05 Hz repetitive squat-stand maneuver to characterize cardiac baroreceptor sensitivity. Plasma norepinephrine levels were assessed during head-up tilt at supine, 30 and 60. Heart rate and BP were monitored during cardiopulmonary exercise testing.
RESULTS
Cardiac baroreceptor sensitivity, determined by Valsalva as well as Fourier transformation and transfer function gain of Heart rate and systolic BP during spontaneous breathing and squat-stand maneuver, was impaired before and following LVAD implantation. Norepinephrine levels were markedly elevated pre-LVAD and improved-but remained elevated post-LVAD (supine norepinephrine pre-LVAD versus post-LVAD: 654±437 versus 323±164 pg/mL). BP increased during cardiopulmonary exercise testing post-LVAD, but the magnitude of change was modest and comparable to the changes observed during the pre-LVAD cardiopulmonary exercise testing.
CONCLUSIONS
Among patients with advanced heart failure with reduced ejection fraction, CF-LVAD implantation is associated with modest improvements in autonomic tone, but persistent reductions in cardiac baroreceptor sensitivity. Exercise-induced increases in BP are blunted. These findings shed new light on mechanisms for adverse events such as stroke, and persistent reductions in functional capacity, among patients supported by CF-LVADs. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03078972.
Topics: Aged; Baroreflex; Blood Pressure; Exercise Test; Female; Heart Failure; Heart Rate; Heart-Assist Devices; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Pressoreceptors; Valsalva Maneuver
PubMed: 33464953
DOI: 10.1161/CIRCHEARTFAILURE.120.007448 -
European Journal of Applied Physiology Mar 2021Heart transplantation (HTx) implies denervation of afferent neural connections. Reinnervation of low-pressure cardiopulmonary baroreceptors might impact the development...
PURPOSE
Heart transplantation (HTx) implies denervation of afferent neural connections. Reinnervation of low-pressure cardiopulmonary baroreceptors might impact the development and treatment of hypertension, but little is known of its occurrence. The present prospective study investigated possible afferent reinnervation of low-pressure cardiopulmonary baroreceptors during the first year after heart transplantation.
METHODS
A total of 50 heart transplant recipients (HTxRs) were included and were evaluated 7-12 weeks after transplant surgery, with follow-up 6 and 12 months later. In addition, a reference group of 50 healthy control subjects was examined once. Continuous, non-invasive recordings of cardiovascular variables were carried out at supine rest, during 15 min of 20° head-up tilt, during Valsalva maneuver and during 1 min of 30% maximal voluntary handgrip. In addition, routine clinical data including invasive measurements were used in the analyses.
RESULTS
During the first year after HTx, the heart rate (HR) response to 20° head-up tilt partly normalized, a negative relationship between resting mean right atrial pressure and HR tilt response developed, low-frequency variability of the RR interval and systolic blood pressure at supine rest increased, and the total peripheral resistance response to Valsalva maneuver became stronger.
CONCLUSION
Functional assessments suggest that afferent reinnervation of low-pressure cardiopulmonary receptors occurs during the first year after heart transplantation, partially restoring reflex-mediated responses to altered cardiac filling.
Topics: Cardiovascular System; Female; Hand Strength; Heart Rate; Heart Transplantation; Humans; Lung; Male; Middle Aged; Pressoreceptors; Prospective Studies
PubMed: 33389144
DOI: 10.1007/s00421-020-04586-0 -
BMC Cardiovascular Disorders Mar 2021The study evaluated the cost of baroreflex activation therapy plus guideline directed therapy (BAT + GDT) compared to GDT alone for HF patients with reduced ejection... (Comparative Study)
Comparative Study
BACKGROUND
The study evaluated the cost of baroreflex activation therapy plus guideline directed therapy (BAT + GDT) compared to GDT alone for HF patients with reduced ejection fraction and New York Heart Association Class III or II (with a recent history of III). Baroreflex activation therapy (BAT) is delivered by an implantable device that stimulates the baroreceptors through an electrode attached to the outside of the carotid artery, which rebalances the autonomic nervous system to regain cardiovascular (CV) homeostasis. The BeAT-HF trial evaluated the safety and effectiveness of BAT.
METHODS
A cost impact model was developed from a U.S. health care payer or integrated delivery network perspective over a 3-year period for BAT + GDT versus GDT alone. Expected costs were calculated by utilizing 6-month data from the BeAT-HF trial and existing literature. HF hospitalization rates were extrapolated based on improvement in NT-proBNP.
RESULTS
At baseline the expected cost of BAT + GDT were $29,526 per patient more than GDT alone due to BAT device and implantation costs. After 3 years, the predicted cost per patient was $9521 less expensive for BAT + GDT versus GDT alone due to lower rates of significant HF hospitalizations, CV non-HF hospitalizations, and resource intensive late-stage procedures (LVADs and heart transplants) among the BAT + GDT group.
CONCLUSIONS
BAT + GDT treatment becomes less costly than GDT alone beginning between years 1 and 2 and becomes less costly cumulatively between years 2 and 3, potentially providing significant savings over time. As additional BeAT-HF trial data become available, the model can be updated to show longer term effects.
Topics: Baroreflex; Chronic Disease; Cost Savings; Cost-Benefit Analysis; Electric Stimulation Therapy; Health Care Costs; Heart Failure; Humans; Models, Economic; Outcome and Process Assessment, Health Care; Pressoreceptors; Time Factors; Treatment Outcome; United States
PubMed: 33771104
DOI: 10.1186/s12872-021-01958-y -
Hypertension Research : Official... Feb 2024Electrode-based electrophysiological interfaces with peripheral nerves have come a long way since the 1960s, with several neurostimulation applications witnessing... (Review)
Review
Electrode-based electrophysiological interfaces with peripheral nerves have come a long way since the 1960s, with several neurostimulation applications witnessing widespread clinical implementation since then. In resistant hypertension, previous clinical trials have shown that "carotid" baroreflex stimulation using device-based baroreflex activation therapy (BAT) can effectively lower blood pressure (BP). However, device-based "aortic" baroreflex stimulation remains untouched for clinical translation. The rat is a remarkable animal model that facilitates exploration of mechanisms pertaining to the baroreceptor reflex and preclinical development of novel therapeutic strategies for BP modulation and hypertension treatment. Specifically, the aortic depressor nerve (ADN) in rats carries a relatively pure population of barosensitive afferent neurons, which enable selective investigation of the aortic baroreflex function. In a rat model of essential hypertension, the spontaneously hypertensive rat (SHR), we have recently investigated the aortic baroreceptor afferents as an alternate target for BP modulation, and showed that "low intensity" stimulation is able to evoke clinically meaningful reductions in BP. Deriving high quality short-term and long-term data on aortic baroreflex modulation in rats is currently hampered by a number of unresolved experimental challenges, including anatomical variations across rats which complicates identification of the ADN, the use of unrefined neurostimulation tools or paradigms, and issues arising from anesthetized and conscious surgical preparations. With the goal of refining existing experimental protocols designed for preclinical investigation of the baroreflex, this review seeks to outline current challenges hindering further progress in aortic baroreflex modulation studies in rats and present some practical considerations and recently emerging ideas to overcome them. Aortic baroreflex modulation.
Topics: Rats; Animals; Baroreflex; Electric Stimulation; Hypertension; Pressoreceptors; Rats, Inbred SHR; Blood Pressure; Heart Rate
PubMed: 37919429
DOI: 10.1038/s41440-023-01486-6