Deterioration in Hemodynamics Reaction, Baroreflex Sensitivity, Sympathetic Nerve Activity and Redox State of Thoracic Aorta in the Experimental Model of Nitrate Tolerance and Its Pharmacological Correction

Continuous treatment with organic nitrates causes nitrate tolerance and provides evidence for a relationship between mitochondrial complex 1 activity and mitochondrial aldehyde dehydrogenase-2 (ALDH-2) with disturbances of the hemodynamics reaction during nitroglycerin (NTG) tolerance (NTGT). The purpose of this study was the evaluation of efficacy of original oxidized form NAD-containing drug, NADCIN®, on hemodynamic reactions, baroreflex sensitivity (BRS) and reflex control of splanchnic sympathetic nerve activity (SSNA), level of redox-potential, activity of ALDH-2 and superoxide anion generation in aortic tissue in rat model of NTGT. Five groups (7 - 9 each) of male Wistar rats, including control, acute i.v. NTG (150 mcg/kg) administration, NTG tolerance NTGT treatment with NADCIN® 8 mg/kg and methylene blue (MB, 2.5 mg/kg) were used. NTGT in rats was accompanied with the greatly attenuation of hemodynamics reaction, BRS, the decreasing of the ability to reflex control of SSNA without pronounce overexpression of endothelin-1 in vessels (aorta). In NTGT rats i.v. NTG along induced less hypotensive reactions and alterations in heart period vs single NTG treated group, more expressively decreased BRS (-34%) and reflex control of SSNA (-18%). NADCIN® significantly inhibits tolerance-inducing properties of the prolonged nitroglycerin infusion (max decrease of blood pressure response to nitroglycerin injection, % of normal controls: NTGT 51.2%, NADCIN® 91.6%, MB 55.8%). NADCIN® in NTGT rats after NTG i.v. administration increased reduced BRS (+37.8%, p < 0,05), reflex control of SSNA (+29.4%, p < 0.05) and reversed the decreasing of NAD/NADH ratio, ALDH-2 activity and decreasing in superoxide generation in thoracic aortic tissue. Thus, course treatment with NADCIN® of NTGT rats restores hemodynamics changes, BRS and SSNA throughout the increasing of redox-potential NAD/NADH and cessates the NTGT developing.

The Changes of Baroreflex Sensitivity During Head-up Tilt Test and Its Clinical Significance in the Patients with Vasovagal Syncope

Objective To study thechanges of baroreflex sensitivity (BRS) during head - up tilt test (HUT) in patients with vasovagal syncope (VS), and to examine the relationship between baroreflex sensitivity and neurohormonal factors. Furthermore, to investigate the effects of the changes of BRS on VS. Methods Forty - two patients with unexplained syncope (Among the 42 patients, there were 22 patients with positive HUT and 20 patients with negative HUT respectively) and 20 healthy volunteers (with negative HUT) underwent passive head - up tilt testing, Ante-cubital vein blood samples were taken before and after HUT, or at syncope. The fasting plasma endothelin , serum nitric oxide (NO), serum NE were measured, the BRS was assessed on the basis of the linear regression slope the RR interval versus systolic arterial blood pressure during the increment in blood pressure after intravenous administration of phenylephrine. Results (1) During the syncope, the BRS significantly reduced in HUT(+) group than baseline. At the end of tilt, the level of plasma ET, serum NO in patients with positive HUT significantly increased compared with baseline or normal controls, and the plasma concentration of NE also had the trend of increase. (2) By multiple regression analysis, a significant negative correlation was found between baroreceptor sensitivity and the plasma ET, NO at the end of HUT in patients with positive HUT, but there was no relationship between BRS and NE. Conclusions During the syncope occure, the BRS in patients with VS decreased significantly compared with normal controls. The abnormal plasma ET, NO concen-tration might contribute to the mechanism of VS.

Exploration of cardiac rehabilitation nursing for elderly patients with myocardial infarction based on individualized cardiac rehabilitation

BACKGROUND Myocardial infarction is a high-risk condition prevalent among the elderly population,often leading to adverse clinical manifestations such as reduced cardiopulmonary function,anxiety,and depression post-surgery.Consequently,cardiac rehabilitation holds immense importance in mitigating these complications.AIM To evaluate the effect of individualized cardiac rehabilitation on blood pressure variability(BPV)and baroreflex sensitivity(BRS)in elderly patients with myocardial infarction.METHODS A cohort of 74 elderly patients diagnosed with myocardial infarction and admitted to our hospital between January 2021 and January 2022 were subjected to random selection.Subsequently,all patients were divided into two groups,namely the research group(n=37)and the control group(n=37),utilizing the number table method.The control group received conventional drug treatment and nursing guidance intervention,while the study group underwent individualized cardiac rehabilitation in addition to the interventions received by the control group.All patients were continuously intervened for 12 wk,and the BPV of these two groups in the 1st wk(T0),the 4th wk(T1)and the 12th wk(T2)were compared,BRS,changes in cardiopulmonary function measures,and adverse cardiovascular events.RESULTS Of 24 h diastolic BPV,24 h systolic BPV,carbon dioxide ventilation equivalent slope of the research group were lower than those of the control group at T1 and T2,BRS,peak heart rate and systolic blood pressure product,1 min heart rate recovery were higher than those of the control group,and the incidence of adverse events in the research group was lower than that of the control group,the difference was statistically significant(P<0.05).CONCLUSION In this study,we found that after individualized cardiac rehabilitation in elderly patients with myocardial infarction,BPV and BRS can be effectively improved,cardiac function is significantly enhanced,and a better prognosis is obtained.

Baroreflex dysfunction in chronic kidney disease

Chronic kidney disease （CKD） patients have high cardiovascular mortality and morbidity. The presence of traditional and CKD related risk factors results in exaggerated vascular calcification in these patients. Vascular calcification is associated with reduced large arterial compliance and thus impaired barorefex sensi-tivity （BRS） resulting in augmented blood pressure （BP） variability and hampered BP regulation. Barorefex plays a vital role in short term regulation of BP. This review discusses the normal barorefex physiology, methods to assess baroreflex function, its determinants along with the prognostic significance of assessing BRS in CKD patients, available literature on BRS in CKD patients and the probable patho-physiology of barorefex dysfunction in CKD.

Successful use of closed-loop allostatic neurotechnology for post-traumatic stress symptoms in military personnel： self-reported and autonomic improvements

Background:Military-related post-traumatic stress(PTS)is associated with numerous symptom clusters and diminished autonomic cardiovascular regulation.Highresolution,relational,resonance-based,electroencephalic mirroringis a noninvasive,closed-loop,allostatic,acoustic stimulation neurotechnology that produces realtime translation of dominant brain frequencies into audible tones of variable pitch and timing to support the autocalibration of neural oscillations.We report clinical,autonomic,and functional effects after the use offor symptoms of military-related PTS.Methods:Eighteen service members or recent veterans(15 active-duty,3 veterans,most from special operations,1 female),with a mean age of 40.9(SD=6.9)years and symptoms of PTS lasting from 1 to 25 years,undertook19.5(SD=1.1)sessions over 12 days.Inventories for symptoms of PTS(Posttraumatic Stress Disorder Checklist–Military version,PCL-M),insomnia(Insomnia Severity Index,ISI),depression(Center for Epidemiologic Studies Depression Scale,CES-D),and anxiety(Generalized Anxiety Disorder 7-item scale,GAD-7)were collected before(Visit1,V1),immediately after(Visit2,V2),and at 1 month(Visit3,V3),3(Visit4,V4),and 6(Visit5,V5)months after intervention completion.Other measures only taken at V1 and V2 included blood pressure and heart rate recordings to analyze heart rate variability(HRV)and baroreflex sensitivity(BRS),functional performance(reaction and grip strength)testing,blood and saliva for biomarkers of stress and inflammation,and blood for epigenetic testing.Paired t-tests,Wilcoxon signed-rank tests,and a repeated-measures ANOVA were performed.Results:Clinically relevant,significant reductions in all symptom scores were observed at V2,with durability through V5.There were significant improvements in multiple measures of HRV and BRS[Standard deviation of the normal beat to normal beat interval(SDNN),root mean square of the successive differences(rMSSD),high frequency(HF),low frequency(LF),and total power,HF alpha,sequence all,and systolic,diastolic and mean arterial pressure]as well as reaction testing.Trends were seen for improved grip strength and a reduction in C-Reactive Protein(CRP),Angiotensin II to Angiotensin 1–7 ratio and Interleukin-10,with no change in DNA n-methylation.There were no dropouts or adverse events reported. Conclusion:Service members or veterans showed reductions in symptomatology of PTS,insomnia,depressive mood,and anxiety that were durable through 6 months after the use of a closed-loop allostatic neurotechnology for the autocalibration of neural oscillations.This study is the first to report increased HRV or BRS after the use of an intervention for service members or veterans with PTS.Ongoing investigations are strongly warranted.Trial registration:NCT03230890,retrospectively registered July 25,2017.

Cardiovascular age of aviation personnel: based on the principal component analysis of heart rate and blood pressure variability

Objective: To introduce a method to calculate cardiovascular age, a new, accurate and much simpler index for assessing cardiovascular autonomic regulatory function, based on statistical analysis of heart rate and blood pressure variability (HRV and BPV) and baroreflex sensitivity (BRS) data. Methods: Firstly, HRV and BPV of 89 healthy aviation personnel were analyzed by the conventional autoregressive (AR) spectral analysis and their spontaneous BRS was obtained by the sequence method. Secondly, principal component analysis was conducted over original and derived indices of HRV, BPV and BRS data and the relevant principal components, PCi orig and PCi deri (i=1, 2, 3,...) were obtained. Finally, the equation for calculating cardiovascular age was obtained by multiple regression with the chronological age being assigned as the dependent variable and the principal components significantly related to age as the regressors. Results: The first four principal components of original indices accounted for over 90% of total variance of the indices, so did the first three principal components of derived indices. So, these seven principal components could reflect the information of cardiovascular autonomic regulation which was embodied in the 17 indices of HRV, BPV and BRS exactly with a minimal loss of information. Of the seven principal components, PC2 orig , PC4 orig and PC2 deri were negatively correlated with the chronological age ( P <0 05), whereas the PC3 orig was positively correlated with the chronological age ( P <0 01). The cardiovascular age thus calculated from the regression equation was significantly correlated with the chronological age among the 89 aviation personnel ( r =0.73, P <0 01). Conclusion: The cardiovascular age calculated based on a multi variate analysis of HRV, BPV and BRS could be regarded as a comprehensive indicator reflecting the age dependency of autonomic regulation of cardiovascular system in healthy aviation personnel.

Nicotinic acetylcholine receptorα7 subunit:a novel therapeutic target for cardiovascular diseases

Inflammation is important in the pathogenesis and development of cardiovascular diseases.Recent studies show that vagus nerve stimulation inhibits pro-inflammatory cytokine production through“the cholinergic anti-inflammatory pathway,”more specifically via theα7 nicotinic acetylcholine receptor(α7nAChR).In the current study,the role of the cholinergic anti-inflammatory pathway during septic shock,hypertension,and myocardial infarction is reviewed,and its possible clinical implications in cardiovascular diseases are discussed.