Arterial Baroreflex Gain Research Articles

Heat stress modifies human baroreflex function independently of heat-induced hypovolemia.

Since human thermoregulatory heat loss responses, cutaneous vasodilation and sweating, cause hypovolemia, they should resultantly stimulate human baroreflexes. However, it is possible that the thermoregulatory system directly interacts with the baroreflex system through central neural connections independently of the heat-induced hypovolemia. We hypothesized that heat stress modifies the baroreflex control of sympathetic nerve activity independently of heat-induced hypovolemia in humans. We made whole-body heating with tube-lined suits perfused with warm water (46-47 degrees C) on 10 healthy male subjects. The heating increased skin and tympanic temperatures by 10.0 and 0.4 degrees C, respectively. It increased resting total muscle sympathetic nerve activity (MSNA, microneurography) by 94 +/- 9% and decreased central venous pressure (CVP, dependent arm technique) by 2.6 +/- 0.9 mmHg. The heating increased arterial baroreflex gain by 193%, assessed as a response of MSNA to a decrease in diastolic arterial pressure during Valsalva's maneuver, but it did not change threshold arterial pressure for MSNA activation. Although the heating did not change the cardiopulmonary baroreflex gain assessed as a response of MSNA to a change in estimated central venous pressure (CVP) during a 10 degrees head-down and -up tilt test, it upwardly shifted the stimulus-response baroreflex relationship. These changes in baroreflex functions during heating were not restored by an intravenous infusion of warmed isotonic saline (37 degrees C, 15 ml/kg) that restored the heat-induced reduction of CVP. Our results support our hypothesis that heat stress modifies the baroreflex control of MSNA independently of heat-induced hypovolemia in humans. Our results also suggest that the hyperthermal modification of baroreflex results from central neural interaction between thermoregulatory and baroreflex systems.

Inter-relations among declines in arterial distensibility, baroreflex function and respiratory sinus arrhythmia

ObjectivesWe hypothesized that structural and neural cardiovascular (CV) deficits may be intimately linked. Specifically, decreased carotid distensibility with age may blunt the arterial baroreflex, thereby reducing resting cardiac vagal tone. BackgroundIncreased CV risk is associated with lower carotid distensibility, impaired baroreflex function and reduced respiratory sinus arrhythmia (RSA), possibly representing a direct path between structural and neural CV deficits. MethodsWe estimated the mechanostructural and neural components of baroreflex function and examined their relation to RSA in young (20 to 31 years) and older (59 to 71 years) subjects rigorously screened for CV and autonomic diseases. ResultsIn the older subjects, RSA was < 20% of that in the younger subjects. Moreover, mechanical transduction of pressure into barosensory vessel stretch was ∼40% lower (p < 0.05) and arterial baroreflex gain more than 60% lower (p < 0.05) in the older group. Although neural transduction of stretch into vagal outflow only tended to be less (p < 0.08), it was an important determinant of baroreflex function. A path analysis model showed comparable contributions of both the mechanical and neural components to baroreflex gain; however, lower overall baroreflex gain in the older group did not relate to lower RSA. ConclusionsThese data suggest that decreased carotid distensibility does reduce baroreflex function with age, but this does not lead to reduced resting vagal outflow.

Simulation study of the cardiovascular functional status in hypertensive situation

An extended cardiovascular model was established based on our previous work to study the consequences of physiological or pathological changes to the homeostatic functions of the cardiovascular system. To study hemodynamic changes in hypertensive situations, the impacts of cardiovascular parameter variations (peripheral vascular resistance, arterial vessel wall stiffness and baroreflex gain) upon hemodynamics and the short-term regulation of the cardiovascular system were investigated. For the purpose of analyzing baroregulation function, the short-term regulation of arterial pressure in response to moderate dynamic exercise for normotensive and hypertensive cases was studied through computer simulation and clinical experiments. The simulation results agree well with clinical data. The results of this work suggest that the model presented in this paper provides a useful tool to investigate the functional status of cardiovascular system in normal or pathological conditions.

Sodium intake influences hemodynamic and neural responses to angiotensin receptor blockade in rostral ventrolateral medulla.

To determine the effects of physiological alterations in endogenous angiotensin II activity on basal renal sympathetic nerve activity (RSNA) and its arterial baroreflex regulation, angiotensin II type 1 receptor antagonists were microinjected into the rostral ventrolateral medulla of anesthetized rats consuming a low, normal, or high sodium diet that were instrumented for simultaneous measurement of arterial pressure and RSNA. Plasma renin activity was increased in rats fed a low sodium diet and decreased in those fed a high sodium diet. Losartan (50, 100, and 200 pmol) decreased heart rate and RSNA (but not mean arterial pressure) dose-dependently; the responses were significantly greater in rats fed a low sodium diet than in those fed a high sodium diet. Candesartan (1, 2, and 10 pmol) decreased mean arterial pressure, heart rate, and RSNA dose-dependently; the responses were significantly greater in rats fed a low sodium diet than in those fed a normal or high sodium diet. [D-Ala(7)]Angiotensin-(1-7) (100, 200, and 1000 pmol) did not affect mean arterial pressure, heart rate, or RSNA in rats fed either a low or a high sodium diet. In rats fed a low sodium diet, candesartan reset the arterial baroreflex control of RSNA to a lower level of arterial pressure, and in rats with congestive heart failure, candesartan increased the arterial baroreflex gain of RSNA. Physiological alterations in the endogenous activity of the renin-angiotensin system influence the bradycardic, vasodepressor, and renal sympathoinhibitory responses to rostral ventrolateral medulla injection of antagonists to angiotensin II type 1 receptors but not to angiotensin-(1-7) receptors.

Enhanced Sympathoexcitatory and Pressor Responses to Chronic Central Sodium Loading in Dahl Salt-Sensitive Vs. -Resistent Rats

P46 Increased responsiveness to increases in CSF Na + by high salt intake may contribute to salt-sensitive hypertension in Dahl S rats. To test this hypothesis, Dahl S and R rats received a chronic icv infusion of artificial CSF (aCSF) or aCSF containing 0.8 M Na + (5 μl/hr) for 14 days, using osmotic minipumps. On day 14 in conscious rats, CSF was sampled and BP, HR and renal sympathetic nerve activity (RSNA) were recorded at rest and in response to air stress, icv α 2 -adrenoceptor agonist guanabenz (50 μg), icv ouabain (0.6 μg), and iv phenylephrine and nitropusside to estimate baroreflex function. Data are mean±SEM (n=8-13). *p + caused more severe hypertension, larger responses to air stress and guanabenz, and more blunting of the arterial baroreflex gain in S vs R rats. These findings suggest that enhanced neuronal responsiveness to CSF Na + is one of the mechanisms contributing to salt-sensitive hypertension in Dahl S rats.

Enhanced Sympathoexcitatory and Pressor Responses to Chronic Central Sodium Loading in Dahl Salt-Sensitive Vs. -Resistent Rats

P46 Increased responsiveness to increases in CSF Na + by high salt intake may contribute to salt-sensitive hypertension in Dahl S rats. To test this hypothesis, Dahl S and R rats received a chronic icv infusion of artificial CSF (aCSF) or aCSF containing 0.8 M Na + (5 μl/hr) for 14 days, using osmotic minipumps. On day 14 in conscious rats, CSF was sampled and BP, HR and renal sympathetic nerve activity (RSNA) were recorded at rest and in response to air stress, icv α 2 -adrenoceptor agonist guanabenz (50 μg), icv ouabain (0.6 μg), and iv phenylephrine and nitropusside to estimate baroreflex function. Data are mean±SEM (n=8-13). *p&lt;0.05 vs others.†p&lt;0.05 vs aCSF. Similar chronic increases in CSF Na + caused more severe hypertension, larger responses to air stress and guanabenz, and more blunting of the arterial baroreflex gain in S vs R rats. These findings suggest that enhanced neuronal responsiveness to CSF Na + is one of the mechanisms contributing to salt-sensitive hypertension in Dahl S rats.

Effects of aging on cardiovascular responses to gravity-related fluid shift in humans.

Fluid shift induced by postural change causes autonomic neural responses of the cardiovascular system that buffer blood pressure fluctuation. The aim of the study was to clarify the effects of aging on cardiovascular autonomic functions in response to gravity-related fluid shift that unloads or loads the baroreceptors in human subjects. A chest electrocardiogram, blood pressure by Finapres, and stroke volume by impedance method were measured in healthy young men (23-31 years old) and healthy elderly men (74-80 years old) during supine rest, at 90 degrees head-up tilt and thermoneutral head-out water immersion. Spectral analysis was applied to the time series data of the R-R intervals (heart rate variability [HRV]) and systolic blood pressure (blood pressure variability [BPV]). The arterial baroreflex gain for heart rate was estimated using frequency transfer function analysis. The young subjects had stable blood pressure, despite the larger amount of fluid shift induced by both tilt and immersion, and had marked changes in HRV and BPV. The elderly subjects failed to maintain stable blood pressure during these perturbations, despite less fluid shift and no significant changes in HRV and BPV. The arterial baroreflex gain for heart rate was not changed in the elderly subjects, whereas the gain decreased with upright in the young subjects and showed an increasing tendency during immersion compared with upright posture. These findings suggest that the adaptivity of the autonomic nervous system to gravity-related fluid shift is reduced in elderly people, and this may cause blood pressure instability.

Selective parasympathetic denervation following posteroseptal ablation for either atrioventricular nodal reentrant tachycardia or accessory pathways

Baroreflex gain and coronary sinus norepinephrine and epinephrine levels were measured before and immediately after radiofrequency ablation in the posteroseptal region in 9 patients with atrioventricular nodal reentrant tachycardia or posteroseptal accessory pathways. Arterial baroreflex gain was significantly reduced after radiofrequency ablation (p = 0.046), whereas coronary sinus epinephrine and norepinephrine levels did not change significantly compared with preablation levels.

Effect of sleep restriction on orthostatic cardiovascular control in humans.

We hypothesized that sleep restriction (4 consecutive nights, 4 h sleep/night) attenuates orthostatic tolerance. The effect of sleep restriction on cardiovascular responses to simulated orthostasis, arterial baroreflex gain, and heart rate variability was evaluated in 10 healthy volunteers. Arterial baroreflex gain was determined from heart rate responses to nitroprusside-phenylephrine injections, and orthostatic tolerance was tested via lower body negative pressure (LBNP). A Finapres device measured finger arterial pressure. No difference in baroreflex function, heart rate variability, or LBNP tolerance was observed with sleep restriction (P > 0.3). Systolic pressure was greater at -60 mmHg LBNP after sleep restriction than before sleep restriction (110 +/- 6 and 124 +/- 3 mmHg before and after sleep restriction, respectively, P = 0.038), whereas heart rate decreased (108 +/- 8 and 99 +/- 8 beats/min before and after sleep restriction, respectively, P = 0.028). These data demonstrate that sleep restriction produces subtle changes in cardiovascular responses to simulated orthostasis, but these changes do not compromise orthostatic tolerance.

Determination of baroreflex gain using auto-regressive moving-average analysis during spontaneous breathing.

The heart rate component of the arterial baroreflex gain (BRG) was determined with auto-regressive moving-average (ARMA) analysis during each of spontaneous (SB) and random breathing (RB) protocols. Ten healthy subjects completed each breathing pattern on two different days in each of two different body positions, supine (SUP) and head-up tilt (HUT). The R-R interval, systolic arterial pressure (SAP) and instantaneous lung volume were recorded continuously. BRG was estimated from the ARMA impulse response relationship of R-R interval to SAP and from the spontaneous sequence method. The results indicated that both the ARMA and spontaneous sequence methods were reproducible (r = 0.76 and r = 0.85, respectively). As expected, BRG was significantly less in the HUT compared to SUP position for both ARMA (mean +/- SEM; 3.5 +/- 0.3 versus 11.2 +/- 1.4 ms mmHg-1; P < 0.01) and spontaneous sequence analysis (10.3 +/- 0.8 versus 31.5 +/- 2.3 ms mmHg-1; P < 0.001). However, no significant difference was found between BRG during RB and SB protocols for either ARMA (7.9 +/- 1.4 versus 6.7 +/- 0.8 ms mmHg-1; P = 0.27) or spontaneous sequence methods (21.8 +/- 2.7 versus 20.0 +/- 2.1 ms mmHg-1; P = 0.24). BRG was correlated during RB and SB protocols (r = 0.80; P < 0.0001). ARMA and spontaneous BRG estimates were correlated (r = 0.79; P < 0.0001), with spontaneous sequence values being consistently larger (P < 0.0001). In conclusion, we have shown that ARMA-derived BRG values are reproducible and that they can be determined during SB conditions, making the ARMA method appropriate for use in a wider range of patients.

Baroreflex gain predicts blood pressure recovery during simulated ventricular tachycardia in humans.

Despite similar degrees of left ventricular dysfunction and similar tachycardia or pacing rate, blood pressure (BP) response and symptoms vary greatly among patients. Sympathetic nerve activity (SNA) increases during sustained ventricular tachycardia (VT), and the magnitude of this sympathoexcitatory response appears to contribute to the net hemodynamic outcome. We hypothesize that the magnitude of sympathoexcitation and thus arterial baroreflex gain is an important determinant of the hemodynamic outcome of VT. We evaluated the relation between arterial baroreflex sympathetic gain and BP recovery during rapid ventricular pacing (VP) in patients referred for electrophysiological study. Efferent postganglionic muscle SNA, BP, and central venous pressure (CVP) were measured in 14 patients during nitroprusside infusion and during VP at 150 (n=12) or 120 (n=2) bpm. Arterial baroreflex gain was defined as the slope of the relationship of change in SNA to change in diastolic BP during nitroprusside infusion. Recovery of mean arterial pressure (MAP) during VP was measured as the increase in MAP from the nadir at the onset of pacing to the steady-state value during sustained VP. Arterial baroreflex gain correlated positively with recovery of MAP (r=0.57, P=0.034). No significant correlation between ejection fraction and baroreflex gain (r=0.48, P=0.08) or BP recovery (r=0.41, P=0.15) was found. When patients were separated into high versus low baroreflex gain, the recovery of MAP during simulated VT was significantly greater in patients with high gain. These data strongly suggest that arterial baroreflex gain contributes significantly to hemodynamic stability during simulated VT. Knowledge of baroreflex gain in individual patients may help the clinician tailor therapy directed toward sustained VT.

Effect of reduced pre-load (tilt manoeuvre), augmented pre-load (leg elevation) and enhanced vagal tone (controlled respiration) on arterial baroreflex gain

Effect of reduced pre-load (tilt manoeuvre), augmented pre-load (leg elevation) and enhanced vagal tone (controlled respiration) on arterial baroreflex gain

Subnormal heart period variability in heart failure: Effect of cardiac transplantation

Heart period variability and arterial baroreceptor-cardiac reflex function were studied in cardiac transplant patients to determine if correction of heart failure restores parasympathetic control mechanisms toward normal. Heart period variability (standard deviation [SD] of 120 consecutive RR or PP intervals) was measured at supine rest in 34 patients with congestive heart failure (23 patients receiving diuretics, digoxin or vasodilators and 11 patients weaned from all medications), 30 cardiac transplant patients (both innervated recipient and denervated donor atrial rates) and 16 age-matched healthy control subjects. Arterial baroreflex gain was evaluated with intravenous bolus injections of phenylephrine in 22 transplant patients.Mean heart period variability (±SEM) was significantly lower (p < 0.05) in the heart failure groups (22 ± 3 ms for medicated and 17 ± 3 ms for nonmedicated) than in the transplant patients (41 ± 5 ms) or control subjects (58 ± 5 ms). Heart period variability of the transplant patients was less than that of the control patients (p < 0.05). A stepwise regression model revealed that heart period variability was inversely related to systolic arterial pressure and directly related to time after transplantation R2= 0.39; p = 0.03) in the transplant patients. Baroreflex gain of normotensive transplant patients was normal (11.7 ± 1.0 ms/mm Hg) and correlated directly with heart period variability (r = 0.62; p < 0.001).These data suggest that subnormal levels of cardiac parasympathetic activity at rest associated with congestive heart failure can be restored progressively toward normal by correction of congestive heart failure after cardiac transplantation. Post-transplant hypertension opposes this correction of baseline parasympathetic activity.

Hypotension 1.5 min after 10% hemorrhage permits evaluation of rabbit's baroreflex.

In seven chronically instrumented rabbits, we studied the influence of the vasopressin system on the evaluation of acute reflex compensation of arterial pressure for a mild hemorrhage. Rabbits were bled 10% of estimated blood volume in 1 min. The hemorrhage was repeated before and after administration of a vasopressin antagonist [d(CH2)5Tyr(Me)arginine vasopressin, 10 micrograms/kg] and in the conscious and anesthetized (pentobarbital sodium 20 mg/kg) state. The efficacy of the vasopressin antagonist was preliminarily tested in each rabbit by confirming its antagonism against the hemodynamic effects of infused vasopressin (50 ng X min-1 X kg-1). Mean arterial pressure (MAP), heart rate (HR), mean aortic flow (MAF), and total peripheral resistance (TPR) were measured before and at 1.5 min after completion of hemorrhage. The hemorrhage caused statistically significant decrease in MAP (84 +/- 6 to 78 +/- 6 mmHg) and MAF (195 +/- 28 to 158 +/- 26 ml X kg-1 X min-1) and increase in TRP (0.44 +/- 0.05 to 0.51 +/- 0.07 mmHg X kg X min X ml-1) and HR (271 +/- 21 to 284 +/- 22 beat/min). However, there was no statistically significant interaction in any variables between vasopressin and hemorrhage, i.e., whether vasopressin was blocked or intact did not affect the fall in MAP by hemorrhage. We conclude that in the rabbit vasopressin's role in the acute compensation of arterial pressure for a quick 10% hemorrhage is small enough to permit accurate estimation of the arterial baroreflex gain from the depressor responses to mild hemorrhage with and without the reflex function.

Combined effects of aortic and right atrial pressures on aortic flow.

Combined effects of aortic and right atrial pressures on aortic flow.