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Journal of Applied Physiology... Oct 2018Autonomic control of blood pressure (BP) and heart rate (HR) is crucial during bleeding and hemorrhagic shock (HS) to compensate for hypotension and hypoxia. Previous...
Autonomic control of blood pressure (BP) and heart rate (HR) is crucial during bleeding and hemorrhagic shock (HS) to compensate for hypotension and hypoxia. Previous works have observed that at the point of hemodynamic decompensation a marked suppression of BP and HR variability occurs, leading to irreversible shock. We hypothesized that recovery of the autonomic control may be decisive for effective resuscitation, along with restoration of mean BP. We computed cardiovascular indexes of baroreflex sensitivity and BP and HR variability by analyzing hemodynamic recordings collected from five pigs during a protocol of severe hemorrhage and resuscitation; three pigs were sham-treated controls. Moreover, we assessed the effects of severe hemorrhage on heart functionality by integrating the hemodynamic findings with measures of plasma high-sensitivity cardiac troponin T and metabolite concentrations in left ventricular (LV) tissue. Resuscitation was performed with fluids and norepinephrine and then by reinfusion of shed blood. After first resuscitation, mean BP reached the target value, but cardiovascular indexes were not fully restored, hinting at a partial recovery of the autonomic mechanisms. Moreover, cardiac troponins were still elevated, suggesting a persistent myocardial sufferance. After blood reinfusion all the indexes returned to baseline. In the harvested heart, LV metabolic profile confirmed the acute stress condition sensed by the cardiomyocytes. Variability indexes and baroreflex trends can be valuable tools to evaluate the severity of HS, and they may represent a more useful end point for resuscitation in combination with standard measures such as mean values and biological measures. NEW & NOTEWORTHY Autonomic control of blood pressure was highly impaired during hemorrhagic shock, and it was not completely recovered after resuscitation despite global restoration of mean pressures. Moreover, a persistent myocardial sufferance emerged from measured cardiac troponin T and metabolite concentrations of left ventricular tissue. We highlight the importance of combining global mean values and biological markers with measures of variability and autonomic control for a better characterization of the effectiveness of the resuscitation strategy.
Topics: Animals; Blood Pressure; Heart; Heart Ventricles; Male; Pressoreceptors; Resuscitation; Shock, Hemorrhagic; Swine; Troponin T
PubMed: 30001154
DOI: 10.1152/japplphysiol.00348.2018 -
PloS One 2015It is not known whether parasympathetic outflow simultaneously acts on bronchial tone and cardiovascular system waxing and waning both systems in parallel, or,...
BACKGROUND
It is not known whether parasympathetic outflow simultaneously acts on bronchial tone and cardiovascular system waxing and waning both systems in parallel, or, alternatively, whether the regulation is more dependent on local factors and therefore independent on each system. The aim of this study was to evaluate the simultaneous effect of different kinds of stimulations, all associated with parasympathetic activation, on bronchomotor tone and cardiovascular autonomic regulation.
METHODS
Respiratory system resistance (Rrs, forced oscillation technique) and cardio-vascular activity (heart rate, oxygen saturation, tissue oxygenation index, blood pressure) were assessed in 13 volunteers at baseline and during a series of parasympathetic stimuli: O2 inhalation, stimulation of the carotid sinus baroreceptors by neck suction, slow breathing, and inhalation of methacholine.
RESULTS
Pure cholinergic stimuli, like O2 inhalation and baroreceptors stimulation, caused an increase in Rrs and a reduction in heart rate and blood pressure. Slow breathing led to bradycardia and hypotension, without significant changes in Rrs. However slow breathing was associated with deep inhalations, and Rrs evaluated at the baseline lung volumes was significantly increased, suggesting that the large tidal volumes reversed the airways narrowing effect of parasympathetic activation. Finally inhaled methacholine caused marked airway narrowing, while the cardiovascular variables were unaffected, presumably because of the sympathetic activity triggered in response to hypoxemia.
CONCLUSIONS
All parasympathetic stimuli affected bronchial tone and moderately affected also the cardiovascular system. However the response differed depending on the nature of the stimulus. Slow breathing was associated with large tidal volumes that reversed the airways narrowing effect of parasympathetic activation.
Topics: Adult; Blood Pressure; Bronchi; Cardiovascular System; Electrocardiography; Female; Healthy Volunteers; Heart Rate; Humans; Male; Methacholine Chloride; Middle Aged; Oxygen; Parasympatholytics; Pressoreceptors; Respiration
PubMed: 26046774
DOI: 10.1371/journal.pone.0127697 -
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 -
Heart rate variability and baroreceptor reflex sensitivity in early- versus late-onset preeclampsia.PloS One 2017To determine whether there are differences in autonomic nervous system function in early- versus late-onset preeclampsia.
OBJECTIVE
To determine whether there are differences in autonomic nervous system function in early- versus late-onset preeclampsia.
METHODS
Matched case-control study. Cases were defined as singleton pregnancies with preeclampsia at < 34+0 weeks of gestation (early-onset preeclampsia) and ≥ 34+0 weeks of gestation (late-onset preeclampsia). For each case in each of the preeclampsia subgroups, three "control"uncomplicated singleton pregnancies were matched by maternal age, height, and week of gestation. Blood pressure and heart rate were measured continuously for 30 minutes in each participant. Baroreceptor reflex sensitivity (assessed using sequence technique), time and frequency domain heart rate variability measures, as SDNN, RMSSD, LFRRI, HFRRI and LF/HFRRI of R-R intervals, were compared between groups (p<0.05 significant).
RESULTS
24 women with preeclampsia (10 with early-onset and 14 with late-onset preeclampsia) and 72 controls were included in the study. SDNN, RMSSD and HFRRI were significantly higher in the late-onset preeclampsia group compared to gestational age matched controls (p = 0.033, p = 0.002 and p = 0.018, respectively). No significant differences in SDNN RMSSD and HFRRI between early-onset preeclampsia group and gestational age matched controls were observed (p = 0.304, p = 0.325 and p = 0.824, respectively). Similarly, baroreceptor reflex sensitivity was higher in late-onset preeclampsia compared to controls at ≥ 34 weeks (p = 0.037), but not different between early-onset preeclampsia compared to controls at < 34 weeks (p = 0.50).
CONCLUSIONS
Heart rate variability and baroreceptor reflex sensitivity are increased in late- but not early-onset preeclampsia compared to healthy pregnancies. This indicates a better autonomic nervous system mediated adaptation to preeclampsia related cardiovascular changes in late-onset disease.
Topics: Adult; Case-Control Studies; Female; Heart Rate; Humans; Pre-Eclampsia; Pregnancy; Pressoreceptors
PubMed: 29053723
DOI: 10.1371/journal.pone.0186521 -
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 -
Journal of Anatomy Nov 2019The glossopharyngeal nerve, via the carotid sinus nerve (CSN), presents baroreceptors from the internal carotid artery (ICA) and chemoreceptors from the carotid body....
The glossopharyngeal nerve, via the carotid sinus nerve (CSN), presents baroreceptors from the internal carotid artery (ICA) and chemoreceptors from the carotid body. Although neurons in the nodose ganglion were labelled after injecting tracer into the carotid body, the vagal pathway to these baro- and chemoreceptors has not been identified. Neither has the glossopharyngeal intracranial afferent/sensory pathway that connects to the brainstem been defined. We investigated both of these issues in male Sprague-Dawley rats (n = 40) by injecting neural tracer wheat germ agglutinin-horseradish peroxidase into: (i) the peripheral glossopharyngeal or vagal nerve trunk with or without the intracranial glossopharyngeal rootlet being rhizotomized; or (ii) the nucleus of the solitary tract right after dorsal and ventral intracranial glossopharyngeal rootlets were dissected. By examining whole-mount tissues and brainstem sections, we verified that only the most rostral rootlet connects to the glossopharyngeal nerve and usually four caudal rootlets connect to the vagus nerve. Furthermore, vagal branches may: (i) join the CSN originating from the pharyngeal nerve base, caudal nodose ganglion, and rostral or caudal superior laryngeal nerve; or (ii) connect directly to nerve endings in the middle segment of the ICA or to chemoreceptors in the carotid body. The aortic depressor nerve always presents and bifurcates from either the rostral or the caudal part of the superior laryngeal nerve. The vagus nerve seemingly provides redundant carotid baro- and chemoreceptors to work with the glossopharyngeal nerve. These innervations confer more extensive roles on the vagus nerve in regulating body energy that is supplied by the cardiovascular, pulmonary and digestive systems.
Topics: Animals; Carotid Artery, Internal; Carotid Body; Chemoreceptor Cells; Male; Neuronal Tract-Tracers; Pressoreceptors; Rats; Rats, Sprague-Dawley; Vagus Nerve
PubMed: 31347697
DOI: 10.1111/joa.13054 -
American Journal of Hypertension May 2016Abnormal baroreceptor function contributes to attenuated arterial baroreflex sensitivity in chronic heart failure (CHF). As a mechanosensor in mammalian nonepithelium,...
BACKGROUND
Abnormal baroreceptor function contributes to attenuated arterial baroreflex sensitivity in chronic heart failure (CHF). As a mechanosensor in mammalian nonepithelium, the epithelial sodium channel (ENaC) is an amiloride-sensitive and voltage-independent ion channel. The ENaC is thought to be a component of baroreceptor mechanosensitive ion channels in aortic baroreceptor cell bodies and nerve terminals. In this study, therefore, we measured the expression and activation of the ENaC in nodose neuronal cell bodies and aortic baroreceptor nerve terminals in sham and CHF rats.
METHODS AND RESULTS
CHF was induced by surgical ligation of left coronary artery. The development of CHF was confirmed by hemodynamic and morphological characteristics. The aortic baroreceptor sensitivity was blunted in anesthetized CHF rats, compared with that in sham rats. The data from immunostaining and western blot analysis showed that the protein of β- and γ-ENaC subunits was expressed in nodose neuronal cell bodies and aortic baroreceptor nerve terminals, whereas the protein of α-ENaC subunit was undetectable. CHF reduced protein expression of β- and γ-ENaC subunits in nodose neuronal cell bodies and aortic baroreceptor nerve terminals. Additionally, the data recorded by the whole cell patch-clamp technique demonstrated that ENaC currents in aortic baroreceptor neurons were lower in CHF rats than that in sham rats.
CONCLUSION
These results suggest that reduced protein expression of the ENaC decreases the ENaC activation, which could be involved in attenuation of the aortic baroreceptor sensitivity in the CHF state. Baroreceptors should be a potential therapeutic target for reducing mortality in CHF.
Topics: Animals; Aorta; Baroreflex; Chronic Disease; Disease Models, Animal; Down-Regulation; Epithelial Sodium Channels; Heart Failure; Hemodynamics; Male; Mechanotransduction, Cellular; Membrane Potentials; Nodose Ganglion; Pressoreceptors; Presynaptic Terminals; Rats, Sprague-Dawley
PubMed: 26297031
DOI: 10.1093/ajh/hpv141 -
Circulation Research Aug 2018Abnormal mechanosensing of smooth muscle cells (SMCs) resulting from the defective elastin-contractile units has been suggested to drive the formation of thoracic aortic...
RATIONALE
Abnormal mechanosensing of smooth muscle cells (SMCs) resulting from the defective elastin-contractile units has been suggested to drive the formation of thoracic aortic aneurysms; however, the precise molecular mechanism has not been elucidated.
OBJECTIVE
The aim of this study was to identify the crucial mediator(s) involved in abnormal mechanosensing and propagation of biochemical signals during the aneurysm formation and to establish a basis for a novel therapeutic strategy.
METHODS AND RESULTS
We used a mouse model of postnatal ascending aortic aneurysms ( Fbln4; termed SMKO [SMC-specific knockout]), in which deletion of Fbln4 (fibulin-4) leads to disruption of the elastin-contractile units caused by a loss of elastic lamina-SMC connections. In this mouse, upregulation of Egr1 (early growth response 1) and angiotensin-converting enzyme leads to activation of Ang II (angiotensin II) signaling. Here, we showed that the matricellular protein, Thbs1 (thrombospondin-1), was highly upregulated in SMKO ascending aortas and in human thoracic aortic aneurysms. Thbs1 was induced by mechanical stretch and Ang II in SMCs, for which Egr1 was required, and reduction of Fbln4 sensitized the cells to these stimuli and led to higher expression of Egr1 and Thbs1. Deletion of Thbs1 in SMKO mice prevented the aneurysm formation in ≈80% of DKO (SMKO;Thbs1 knockout) animals and suppressed Ssh1 (slingshot-1) and cofilin dephosphorylation, leading to the formation of normal actin filaments. Furthermore, elastic lamina-SMC connections were restored in DKO aortas, and mechanical testing showed that structural and material properties of DKO aortas were markedly improved.
CONCLUSIONS
Thbs1 is a critical component of mechanotransduction, as well as a modulator of elastic fiber organization. Maladaptive upregulation of Thbs1 results in disruption of elastin-contractile units and dysregulation of actin cytoskeletal remodeling, contributing to the development of ascending aortic aneurysms in vivo. Thbs1 may serve as a potential therapeutic target for treating thoracic aortic aneurysms.
Topics: Actin Cytoskeleton; Aged; Aged, 80 and over; Animals; Aorta, Thoracic; Aortic Aneurysm, Thoracic; Cells, Cultured; Cofilin 2; Dilatation, Pathologic; Disease Models, Animal; Early Growth Response Protein 1; Elastic Tissue; Elastin; Extracellular Matrix Proteins; Female; Humans; Male; Mechanotransduction, Cellular; Mice, Knockout; Middle Aged; Muscle, Smooth, Vascular; Phosphoprotein Phosphatases; Phosphorylation; Pressoreceptors; Rats; Stress, Mechanical; Thrombospondin 1; Vascular Remodeling
PubMed: 30355232
DOI: 10.1161/CIRCRESAHA.118.313105 -
American Journal of Physiology.... Mar 2021Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that is associated with many cardiovascular complications. Similar to OSA, chronic intermittent...
Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that is associated with many cardiovascular complications. Similar to OSA, chronic intermittent hypoxia (CIH) (a model for OSA) leads to oxidative stress and impairs baroreflex control of the heart rate (HR) in rodents. The baroreflex arc includes the aortic depressor nerve (ADN), vagal efferent, and central neurons. In this study, we used mice as a model to examine the effects of CIH on baroreflex sensitivity, aortic baroreceptor afferents, and central and vagal efferent components of the baroreflex circuitry. Furthermore, we tested whether human Cu/Zn Superoxide Dismutase (SOD1) overexpression in transgenic mice offers protection against CIH-induced deficit of the baroreflex arc. Wild-type C57BL/6J and SOD1 mice were exposed to room air (RA) or CIH and were then anesthetized, ventilated, and catheterized for measurement of mean arterial pressure (MAP) and HR. Compared with wild-type RA control, CIH impaired baroreflex sensitivity but increased maximum baroreceptor gain and bradycardic response to vagal efferent stimulation. Additionally, CIH reduced the bradycardic response to ADN stimulation, indicating a diminished central regulation of bradycardia. Interestingly, SOD1 overexpression prevented CIH-induced attenuation of HR responses to ADN stimulation and preserved HR responses to vagal efferent stimulation in transgenic mice. We suggest that CIH decreased central mediation of the baroreflex and SOD1 overexpression may prevent the CIH-induced central deficit.
Topics: Animals; Arterial Pressure; Baroreflex; Bradycardia; Brain; Cardiovascular System; Chronic Disease; Disease Models, Animal; Electric Stimulation; Heart Rate; Humans; Hypoxia; Male; Mice, Inbred C57BL; Mice, Transgenic; Pressoreceptors; Superoxide Dismutase-1; Up-Regulation; Vagus Nerve; Mice
PubMed: 33296277
DOI: 10.1152/ajpregu.00147.2020