Cardiovagal Baroreflex Hysteresis Using Ellipses in Response to Postural Changes

The cardiovagal branch of the baroreflex is of high clinical relevance when detecting disturbances of the autonomic nervous system. The hysteresis of the baroreflex is assessed using provoked and spontaneous changes in blood pressure. We propose a novel ellipse analysis to characterize hysteresis of the spontaneous respiration-related cardiovagal baroreflex for orthostatic test. Up and down sequences of pressure changes as well as the working point of baroreflex are considered. The EuroBaVar data set for supine and standing was employed to extract heartbeat intervals and blood pressure values. The latter values formed polygons into which a bivariate normal distribution was fitted with its properties determining proposed ellipses of baroreflex. More than 80% of ellipses are formed out of nonoverlapping and delayed up and down sequences highlighting baroreflex hysteresis. In the supine position, the ellipses are more elongated (by about 46%) and steeper (by about 4.3° as median) than standing, indicating larger heart interval variability (70.7 versus 47.9 ms) and smaller blood pressure variability (5.8 versus 8.9 mmHg) in supine. The ellipses show a higher baroreflex sensitivity for supine (15.7 ms/mmHg as median) than standing (7 ms/mmHg). The center of the ellipse moves from supine to standing, which describes the overall sigmoid shape of the baroreflex with the moving working point. In contrast to regression analysis, the proposed method considers gain and set-point changes during respiration, offers instructive insights into the resulting hysteresis of the spontaneous cardiovagal baroreflex with respiration as stimuli, and provides a new tool for its future analysis.

346 Baroreflex sensitivity and autonomic function in Takotsubo syndrome long after the acute phase

Aims Takotsubo Syndrome (TS) occurs as an acute coronary syndrome (ACS) characterized by severe left ventricular (LV) dysfunction that typically recovers spontaneously within days or weeks and in the absence of obstructive coronary artery disease. Although during the acute phase it is well documented that an exaggerated sympathetic tone plays a central role in the development of TS, whether an impaired sympatho-vagal balance may persist long after the acute phase, despite the recovery of left ventricular function, is still an open issue. Interestingly, recent evidences suggest that an impairment in central autonomic network not only persist long after the acute event but also may be pre-existent before the acute onset of TS. The Aim of the study was to investigate whether an impairment of the autonomic function is still present long after a TS event. Methods and results We evaluated 67 patients (91% female, mean age 66 ± 8 years) divided into three groups: 24 with a history of TS (1 year after acute event), 21 subjects with a previous history of acute coronary syndrome (ACS) and complete LV ejection fraction recovery (1 year after acute event) and 22 age- and gender-matched healthy subjects. All patients underwent a non-invasive beat-to-beat arterial blood pressure and heart rate recording (short term: 5 min), after at least 3 days of β-blockers wash-out, to obtain heart rate variability (HRV) and spontaneous baroreflex sensitivity (sBRS) data. An overall autonomic dysfunction was found in both TS and ACS groups compared to controls. In particular, a lower heart rate variability, expressed as lower SDNN, has been found in TS and ACS groups compared to controls (31 ± 12 vs. 25 ± 11 vs. 41 ± 22; P = 0.006—Figure A) as a consequence of blunted vagal tone, expressed as lower RMSSD (20 ± 12 vs. 19 ± 11 vs. 40 ± 37; P = 0.007—Figure B) and higher sympathetic tone, expressed as higher LF/HF ratio (P = 0.007 Figure C) which was found to be higher in TS even when compared to ACS (TS: 3.5 ± 2.5 vs. ACS: 2.1 ± 1.7; P = 0.011). Moreover, fractal analysis of HRV showed higher complexity of heart rate regulation, expressed as higher fractal dimension (DFA 1.48 ± 0.06 vs. 1.53 ± 0.05 vs. 1.40 ± 0.10; P < 0.0001—Figure D), in both TS and ACS compared to controls. Interestingly, spontaneous BRS showed the lowest values in the TS group (sSBP: 5.6 ± 2.6 vs. 7.5 ± 3.0 vs. 12.1 ± 11.9; P = 0.027—Figure E), associated with highest levels of sympathetic peripheral control of systolic blood pressure (SBP), expressed as LF-BRS (13.7 ± 9.6 vs. 8.3 ± 5.2 ± 6.8 ± 5.8; P = 0.008—Figure F). Conclusions An autonomic dysfunction, characterized by a hyper-sympathetic tone, reduced baroreflex sensitivity and increased peripheral adrenergic control of blood pressure, persists in TS patients long after the acute phase.

Vasoconstriction Response to Mental Stress in Sickle Cell Disease: The Role of the Cardiac and Vascular Baroreflexes

Recent studies have shown that individuals with sickle cell disease (SCD) exhibit greater vasoconstriction responses to physical autonomic stressors, such as heat pain and cold pain than normal individuals, but this is not the case for mental stress (MTS). We sought to determine whether this anomalous finding for MTS is related to inter-group differences in baseline cardiac and vascular autonomic function. Fifteen subjects with SCD and 15 healthy volunteers participated in three MTS tasks: N-back, Stroop, and pain anticipation (PA). R–R interval (RRI), arterial blood pressure and finger photoplethysmogram (PPG) were continuously monitored before and during these MTS tasks. The magnitude of vasoconstriction was quantified using change in PPG amplitude (PPGa) from the baseline period. To represent basal autonomic function, we assessed both cardiac and vascular arms of the baroreflex during the baseline period. Cardiac baroreflex sensitivity (BRSc) was estimated by applying both the “sequence” and “spectral” techniques to beat-to-beat measurements of systolic blood pressure and RRIs. The vascular baroreflex sensitivity (BRSv) was quantified using the same approaches, modified for application to beat-to-beat diastolic blood pressure and PPGa measurements. Baseline BRSc was not different between SCD and non-SCD subjects, was not correlated with BRSv, and was not associated with the vasoconstriction responses to MTS tasks. BRSv in both groups was correlated with mean PPGa, and since both baseline PPGa and BRSv were lower in SCD, these results suggested that the SCD subjects were in a basal state of higher sympathetically mediated vascular tone. In both groups, baseline BRSv was positively correlated with the vasoconstriction responses to N-back, Stroop, and PA. After adjusting for differences in BRSv within and between groups, we found no difference in the vasoconstriction responses to all three mental tasks between SCD and non-SCD subjects. The implications of these findings are significant in subjects with SCD since vasoconstriction reduces microvascular flow and prolongs capillary transit time, increasing the likelihood for vaso-occlusive crisis (VOC) to be triggered by exposure to stressful events.

Effects of Greater Central Arterial Stiffness on Cardiovagal Baroreflex Sensitivity in Resistance-Trained Men

Background Compared with age-matched untrained men, resistance-trained men who have undergone long duration training (> 2 years) at a high frequency (> 5 days/week) may be lower cardiovagal baroreflex sensitivity (BRS) because of central arterial stiffening. Therefore, the purpose of this study was to examine the effect of greater central arterial stiffness in resistance-trained men on cardiovagal BRS in a cross-sectional study to compare resistance-trained men with age-matched untrained men. Methods This cross-sectional study included resistance-trained men (n = 20; age: 22 ± 3; body mass index: 26.7 ± 2.2) and age-matched untrained men (control group: n = 20; age: 25 ± 2; body mass index: 23.7 ± 2.4). The β-stiffness index and arterial compliance were assessed at the right carotid artery using a combination of a brightness mode ultrasonography system for the carotid artery diameter and applanation tonometry for the carotid blood pressure. And, the cardiovagal BRS was estimated by the slope of the R–R interval and systolic blood pressure during Phase II and IV of Valsalva maneuver (VM). The participants maintained an expiratory mouth pressure of 40 mmHg for 15 s in the supine position. Results The β-Stiffness index was significantly higher in the resistance-trained group than in the control group (5.9 ± 1.4 vs. 4.4 ± 1.0 a.u., P < 0.01). In contrast, the resistance-trained group had significantly lower arterial compliance (0.15 ± 0.05 vs. 0.20 ± 0.04 mm2/mmHg, P < 0.01) and cardiovagal BRS during Phase IV of VM (9.0 ± 2.5 vs. 12.9 ± 5.4 ms/mmHg, P < 0.01) than the control group and. Moreover, cardiovagal BRS during Phase IV of VM was inversely and positively correlated with the β-stiffness index (r = − 0.59, P < 0.01) and arterial compliance (r = 0.64, P < 0.01), respectively. Conclusion Resistance-trained group had greater central arterial stiffness and lower cardiovagal BRS Phase IV compared with control group. Moreover, the central arterial stiffening was related to cardiovagal BRS Phase IV. These results suggest that greater central arterial stiffness in resistance-trained men may be associated with lower cardiovagal BRS. Trial Registration University hospital Medical Information Network (UMIN) in Japan, UMIN000038116. Registered on September 27, 2019.

Midlife Aerobic Exercise and Dynamic Cerebral Autoregulation: Associations with Baroreflex Sensitivity and Central Arterial Stiffness

Midlife aerobic exercise may significantly impact age-related changes in the cerebro- and cardiovascular regulations. This study investigated the associations of midlife aerobic exercise with dynamic cerebral autoregulation (dCA), cardiovagal baroreflex sensitivity (BRS), and central arterial stiffness. Twenty middle-aged athletes (MA) who had aerobic training for >10 years were compared with 20 young (YS) and 20 middle-aged sedentary (MS) adults. Beat-to-beat cerebral blood flow velocity, blood pressure (BP), and heart rate were measured at rest and during forced BP oscillations induced by repeated sit-stand maneuvers at 0.05 Hz. Transfer function analysis was used to calculate dCA and BRS parameters. Carotid distensibility was measured by ultrasonography. MA had the highest peak oxygen uptake (VO2peak) among all groups. During forced BP oscillations, MS showed lower BRS gain than YS, but this age-related reduction was absent in MA. Conversely, dCA was similar among all groups. At rest, BRS and dCA gains at low frequency (~0.1 Hz) were higher in the MA compared with MS and YS groups. Carotid distensibility was similar between MA and YS groups, but it was lower in the MS. Across all subjects, VO2peak was positively associated with BRS gains at rest and during forced BP oscillations (r=0.257~0.382, p=0.003~0.050) and carotid distensibility (r=0.428~0.490, p=0.001). Furthermore, dCA gain at rest and carotid distensibility were positively correlated with BRS gain at rest in YS and MA groups (all p<0.05). These findings suggest that midlife aerobic exercise improves central arterial elasticity and BRS which may contribute to CBF regulation through dCA.

Dexamethasone attenuates the modulatory effect of the insular cortex on the baroreflex in anesthetized rat

The arterial baroreflex (BR) is an important neural mechanism for the stabilization of arterial pressure (AP). It is known that the insular cortex (IC) and other parts of the central autonomic network (CAN) are able to modulate the BR arc, altering baroreflex sensitivity (BRS). In addition, the sensitivity of the BR changes under the influence of hormones, in particular glucocorticoids (GC). It has been suggested that GC may influence BRS by altering the ability of the IC to modulate the BR. This hypothesis has been tested in experiments on rats anesthetized with urethane. It was found that microelectrostimulation of the visceral area in the left IC causes a short-term drop in AP, which is accompanied by bradycardia, and impairs BRS. The synthetic GC dexamethasone (DEX) did not significantly affect the magnitude of depressor responses but increased BRS and impaired the effect of IC stimulation on the BR. The results obtained confirm the hypothesis put forward and suggest that GC can attenuate the inhibitory effects of the IC on the BR arc, thereby enhancing the sensitivity of the BR.

A closed-loop approach to the study of the baroreflex dynamics during posture changes at rest and at exercise in humans

We hypothesized that during rapid up-tilting at rest, due to vagal withdrawal, arterial baroreflex sensitivity (BRS) may decrease promptly and precede the operating point (OP) resetting, whereas different kinetics are expected during exercise steady state, due to lower vagal activity than at rest. To test this, eleven subjects were rapidly (< 2s) tilted from supine (S) to upright (U) and vice versa every 3 minutes, at rest and during steady state 50W pedaling. Mean arterial pressure (MAP) was measured by finger cuff (Portapres) and R-to-R interval (RRi) by electrocardiography. BRS was computed with the sequence method both during steady and unsteady states. At rest, BRS was 35.1ms∙mmHg-1 (SD17.1) in S and 16.7ms∙mmHg-1 (SD6.4) in U (p<0.01), RRi was 901ms (SD118) in S and 749ms (SD98) in U (p<0.01), and MAP was 76mmHg (SD11) in S and 83mmHg (SD8) in U (p<0.01). During up-tilt, BRS decreased promptly [first BRS sequence was 19.7ms∙mmHg-1 (SD5.0)] and was followed by an OP resetting (MAP increase without changes in RRi). At exercise, BRS and OP did not differ between supine and upright positions [respectively, BRS was 7.7ms∙mmHg-1 (SD3.0) and 7.7ms∙mmHg-1 (SD3.5), MAP was 85mmHg (SD13) and 88mmHg (SD10), and RRi was 622ms (SD61) and 600ms (SD70)]. The results support the tested hypothesis. The prompt BRS decrease during up-tilt at rest may be ascribed to a vagal withdrawal, similarly to what occurs at exercise onset. The OP resetting may be due to a slower control mechanism, possibly an increase in sympathetic activity.

Effects of Lifestyle Modification on Patients With Resistant Hypertension: Results of the TRIUMPH Randomized Clinical Trial

Background: Although lifestyle modifications generally are effective in lowering blood pressure (BP) among patients with unmedicated hypertension and in those treated with 1 or 2 antihypertensive agents, the value of exercise and diet for lowering BP in patients with resistant hypertension is unknown. Methods: One hundred forty patients with resistant hypertension (mean age, 63 years; 48% female; 59% Black; 31% with diabetes; 21% with chronic kidney disease) were randomly assigned to a 4-month program of lifestyle modification (C-LIFE [Center-Based Lifestyle Intervention]) including dietary counseling, behavioral weight management, and exercise, or a single counseling session providing SEPA (Standardized Education and Physician Advice). The primary end point was clinic systolic BP; secondary end points included 24-hour ambulatory BP and select cardiovascular disease biomarkers including baroreflex sensitivity to quantify the influence of the baroreflex on heart rate, high-frequency heart rate variability to assess vagally mediated modulation of heart rate, flow-mediated dilation to evaluate endothelial function, pulse wave velocity to assess arterial stiffness, and left ventricular mass to characterize left ventricular structure. Results: Between-group comparisons revealed that the reduction in clinic systolic BP was greater in C-LIFE (–12.5 [95% CI, –14.9 to –10.2] mm Hg) compared with SEPA(–7.1 [–95% CI, 10.4 to –3.7] mm Hg) ( P =0.005); 24-hour ambulatory systolic BP also was reduced in C-LIFE (–7.0 [95% CI, –8.5 to –4.0] mm Hg), with no change in SEPA (–0.3 [95% CI, –4.0 to 3.4] mm Hg) ( P =0.001). Compared with SEPA, C-LIFE resulted in greater improvements in resting baroreflex sensitivity (2.3 ms/mm Hg [95% CI, 1.3 to 3.3] versus –1.1 ms/mm Hg [95% CI, –2.5 to 0.3]; P <0.001), high-frequency heart rate variability (0.4 ln ms 2 [95% CI, 0.2 to 0.6] versus –0.2 ln ms 2 [95% CI, –0.5 to 0.1]; P <0.001), and flow-mediated dilation (0.3% [95% CI, –0.3 to 1.0] versus –1.4% [95% CI, –2.5 to –0.3]; P =0.022). There were no between-group differences in pulse wave velocity ( P =0.958) or left ventricular mass ( P =0.596). Conclusions: Diet and exercise can lower BP in patients with resistant hypertension. A 4-month structured program of diet and exercise as adjunctive therapy delivered in a cardiac rehabilitation setting results in significant reductions in clinic and ambulatory BP and improvement in selected cardiovascular disease biomarkers. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02342808.