Incommensurate frequencies of major vascular regulatory mechanisms.

The dynamic relationship among three major vascular control mechanisms that operate on large fractions of cardiac output: arterial baroreflex and renal and mesenteric autoregulation, was investigated in conscious rats. Wistar and spontaneously hypertensive rats were studied in their home cages 10 days after implantation of pulsed Doppler flow probes. There was an oscillation of blood pressure centered at 0.45 Hz that is associated with operation of arterial baroreflexes. Hindquarters blood flow displayed a featureless, "1/f' power spectrum, in which no autoregulatory or baroreflex signatures could be discerned, although active control of resistance over a wide range of frequencies was evident. The renal pressure - flow transfer function was dominated by an autoregulatory mechanism with a resonance peak at 0.25 +/- 0.01 Hz. In the mesenteric circulation an autoregulatory mechanism was seen with a resonance peak at 0.15 +/- 0.01 Hz and another active mechanism was seen above 0.2 Hz that appeared from its negative admittance phase to be a baroreflex. The center frequencies of mesenteric and renal autoregulation and of the arterial baroreflex were related in a ratio of 1 : 1.7 +/- 0.1 : 3.0 +/- 0.2 (approximately 4:7:12). Such relatively high order ratios can be expected to minimize the possibility of phase locking and (or) entrainment among the various control mechanisms.     

Carotid and aortic baroreflexes of the rat: II. Open-loop frequency response and the blood pressure spectrum

To determine the relationship between blood pressure (BP) variability and the open-loop frequency domain transfer function (TF) of the baroreflexes, we measured the pre- and postsinoaortic denervation (SAD) spectra and the effects of periodic and step inputs to the aortic depressor nerve and isolated carotid sinus of central nervous system-intact, neuromuscular-blocked (NMB) rats. Similar to previous results in freely moving rats, SAD greatly increased very low frequency (VLF) (0.01-0.2 Hz) systolic blood pressure (SBP) noise power. Step response-frequency measurements for SBP; interbeat interval (IBI); venous pressure; mesenteric, femoral, and skin blood flow; and direct modulation analyses of SBP showed that only VLF variability could be substantially attenuated by an intact baroreflex. The -3-dB frequency for SBP is 0.035-0.056 Hz; femoral vascular conductance is similar to SBP, but mesenteric vascular conductance has a reliably lower and IBI has a reliably higher -3-dB point. The overall open-loop transportation lag, of which 相似文献   

Estimation of arterial and cardiopulmonary total peripheral resistance baroreflex gain values: validation by chronic arterial baroreceptor denervation

Feedback control of total peripheral resistance (TPR) by the arterial and cardiopulmonary baroreflex systems is an important mechanism for short-term blood pressure regulation. Existing methods for measuring this TPR baroreflex mechanism typically aim to quantify only the gain value of one baroreflex system as it operates in open-loop conditions. As a result, the normal, integrated functioning of the arterial and cardiopulmonary baroreflex control of TPR remains to be fully elucidated. To this end, the laboratory of Mukkamala et al. (Mukkamala R, Toska K, and Cohen RJ. Am J Physiol Heart Circ Physiol 284: H947-H959, 2003) previously proposed a potentially noninvasive technique for estimating the closed-loop (dimensionless) gain values of the arterial TPR baroreflex (GA) and the cardiopulmonary TPR baroreflex (GC) by mathematical analysis of the subtle, beat-to-beat fluctuations in arterial blood pressure, cardiac output, and stroke volume. Here, we review the technique with additional details and describe its experimental evaluation with respect to spontaneous hemodynamic variability measured from seven conscious dogs, before and after chronic arterial baroreceptor denervation. The technique was able to correctly predict the group-average changes in GA and GC that have previously been shown to occur following chronic arterial baroreceptor denervation. That is, reflex control by the arterial TPR baroreflex was virtually abolished (GA = -2.1 +/- 0.6 to 0.3 +/- 0.2; P < 0.05), while reflex control by the cardiopulmonary TPR baroreflex more than doubled (GC = -0.7 +/- 0.4 to -1.8 +/- 0.2; P < 0.05). With further successful experimental testing, the technique may ultimately be employed to advance the basic understanding of TPR baroreflex functioning in both humans and animals in health and disease.     

Effects of lower body negative pressure on cardiac and vascular responses to carotid baroreflex stimulation

The aim of this study was to assess carotid baroreflex responses during graded lower body negative pressure (LBNP). In 12 healthy subjects (age 29+/-4 years) we applied sinusoidal neck suction (0 to -30 mmHg) at 0.1 Hz to examine the sympathetic modulation of the heart and blood vessels and at 0.2 Hz to assess the effect of parasympathetic stimulation on the heart. Responses to neck suction were determined as the change in spectral power of RR-interval and blood pressure from baseline values. Measurements were carried out during progressive applications (0 to -50 mmHg) of LBNP. Responses to 0.1 and 0.2 Hz carotid baroreceptor stimulations during low levels of LBNP (-10 mmHg) were not significantly different from those measured during baseline. At higher levels of LBNP, blood pressure responses to 0.1 Hz neck suction were significantly enhanced, but with no significant change in the RR-interval response. LBNP at all levels had no effect on the RR-interval response to 0.2 Hz neck suction. The unchanged responses of RR-interval and blood pressure to neck suction during low level LBNP at -10 mmHg suggest no effect of cardiopulmonary receptor unloading on the carotid arterial baroreflex, since this LBNP level is considered to stimulate cardiopulmonary but not arterial baroreflexes. Enhanced blood pressure responses to neck suction during higher levels of LBNP are not necessarily the result of a reflex interaction but may serve to protect the circulation from fluctuations in blood pressure while standing.     

Effects of whole body heating on dynamic baroreflex regulation of heart rate in humans

The purpose of this project was to identify whether dynamic baroreflex regulation of heart rate (HR) is altered during whole body heating. In 14 subjects, dynamic baroreflex regulation of HR was assessed using transfer function analysis. In normothermic and heat-stressed conditions, each subject breathed at a fixed rate (0. 25 Hz) while beat-by-beat HR and systolic blood pressure (SBP) were obtained. Whole body heating significantly increased sublingual temperature, HR, and forearm skin blood flow. Spectral analysis of HR and SBP revealed that the heat stress significantly reduced HR and SBP variability within the high-frequency range (0.2-0.3 Hz), reduced SBP variability within the low-frequency range (0.03-0.15 Hz), and increased the ratio of low- to high-frequency HR variability (all P < 0.01). Transfer function gain analysis showed that the heat stress reduced dynamic baroreflex regulation of HR within the high-frequency range (from 1.04 +/- 0.06 to 0.54 +/- 0.6 beats. min(-1). mmHg(-1); P < 0.001) without significantly affecting the gain in the low-frequency range (P = 0.63). These data suggest that whole body heating reduced high-frequency dynamic baroreflex regulation of HR associated with spontaneous changes in blood pressure. Reduced vagal baroreflex regulation of HR may contribute to reduced orthostatic tolerance known to occur in humans during heat stress.     

Neural and humoral control of regional vascular beds via A1 adenosine receptors located in the nucleus tractus solitarii

Our previous studies showed that stimulation of adenosine A(1) receptors located in the nucleus of the solitary tract (NTS) exerts counteracting effects on the iliac vascular bed: activation of the adrenal medulla and β-adrenergic vasodilation vs. sympathetic and vasopressinergic vasoconstriction. Because NTS A(1) adenosine receptors inhibit baroreflex transmission in the NTS and contribute to the pressor component of the HDR, we hypothesized that these receptors also contribute to the redistribution of blood from the visceral to the muscle vasculature via prevailing sympathetic and vasopressinergic vasoconstriction in the visceral (renal and mesenteric) vascular beds and prevailing β-adrenergic vasodilation in the somatic (iliac) vasculature. To test this hypothesis, we compared the A(1) adenosine-receptor-mediated effects of each vasoactive factor triggered by NTS A(1) adenosine receptor stimulation [N(6)-cyclopentyladenosine (CPA), 330 pmol in 50 nl] on the regional vascular responses in urethane/chloralose-anesthetized rats. The single-factor effects were separated using adrenalectomy, β-adrenergic blockade, V(1) vasopressin receptor blockade, and sinoaortic denervation. In intact animals, initial vasodilation was followed by large, sustained vasoconstriction with smaller responses observed in renal vs. mesenteric and iliac vascular beds. The initial β-adrenergic vasodilation prevailed in the iliac vs. mesenteric and renal vasculature. The large and sustained vasopressinergic vasoconstriction was similar in all vascular beds. Small sympathetic vasoconstriction was observed only in the iliac vasculature in this setting. We conclude that, although A(1) adenosine-receptor-mediated β-adrenergic vasodilation may contribute to the redistribution of blood from the visceral to the muscle vasculature, this effect is overridden by sympathetic and vasopressinergic vasoconstriction.     

Reduced baroreflex control of heart period after bed rest is normalized by acute plasma volume restoration

Adaptation to spaceflight or head-down-tilt bed rest leads to hypovolemia and an apparent abnormality of baroreflex regulation of cardiac period. In a previous study, we demonstrated that both chronic (2 wk) head-down-tilt bed rest and acute induced hypovolemia led to similar impairments in spontaneous baroreflex control of cardiac period, suggesting that a reduction in plasma volume may be responsible for this abnormality after bed rest. Therefore we hypothesized that this reduced "baroreflex function" could be restored by intravenous volume infusion equivalent to the reduction in plasma volume after bed rest. Six healthy subjects underwent 2 wk of -6 degrees head-down bed rest. Beat-by-beat arterial blood pressure and ECG were recorded during 6 min of spontaneous respiration and fixed-rate breathing (0.2 Hz), and transfer function analysis between systolic blood pressure and R-R interval was performed. Plasma volume was measured with Evans blue dye, and cardiac filling pressures were directly measured (Swan-Ganz catheter). After bed rest, studies were repeated before and after plasma volume restoration, with which both plasma volume and left ventricular end-diastolic pressure were restored to pre-bed rest levels by intravenous dextran40 infusion (288 +/- 31 ml). Transfer function gain in the high-frequency range, used as an index of vagally mediated arterial-cardiac baroreflex function, decreased significantly (13.4 +/- 3.1 to 8.1 +/- 2.9 ms/mmHg, P < 0.05) after bed rest. However, reduced transfer function gain was normalized to the pre-bed rest level (12.2 +/- 3.6 ms/mmHg) after precise plasma volume restoration. This result confirms that reductions in plasma volume, rather than a unique autonomic nervous system adaptation to bed rest, are largely responsible for the observed changes in spontaneous arterial-cardiac baroreflex function after bed rest.     

Muscle mechanoreflex augments arterial baroreflex-mediated dynamic sympathetic response to carotid sinus pressure

Although the muscle mechanoreflex is one of the pressor reflexes during exercise, its interaction with dynamic characteristics of the arterial baroreflex remains to be quantitatively analyzed. In anesthetized, vagotomized, and aortic-denervated rabbits (n = 7), we randomly perturbed isolated carotid sinus pressure (CSP) using binary white noise while recording renal sympathetic nerve activity (SNA) and arterial pressure (AP). We estimated the transfer functions of the baroreflex neural arc (CSP to SNA) and peripheral arc (SNA to AP) under conditions of control and muscle stretch of the hindlimb (5 kg of tension). The muscle stretch increased the dynamic gain of the neural arc while maintaining the derivative characteristics [gain at 0.01 Hz: 1.0 +/- 0.2 vs. 1.4 +/- 0.6 arbitrary units (au)/mmHg, gain at 1 Hz: 1.7 +/- 0.6 vs. 2.7 +/- 1.4 au/mmHg; P < 0.05, control vs. stretch]. In contrast, muscle stretch did not affect the peripheral arc. In the time domain, muscle stretch augmented the steady-state response at 50 s (-1.1 +/- 0.3 vs. -1.7 +/- 0.7 au; P < 0.05, control vs. stretch) and negative peak response (-2.1 +/- 0.5 vs. -3.1 +/- 1.5 au; P < 0.05, control vs. stretch) in the SNA step response. A simulation experiment using the results indicated that the muscle mechanoreflex would accelerate the closed-loop AP regulation via the arterial baroreflex.     

The Influence of Tobacco Smoking on the Relationship between Pressure and Flow in the Middle Cerebral Artery in Humans

Background

Cigarette smoking is associated with an increased risk of stroke but the mechanism is unclear. The study examined whether acute and chronic cigarette smoking alters the dynamic relationship between blood pressure and cerebral blood flow. We hypothesised that acute and chronic smoking would result in a cerebral circulation that was less capable of buffering against dynamic fluctuations in blood pressure. Further, these changes would be accompanied by a reduction in baroreflex sensitivity, which is reduced after smoking (acute smoking).

Methods

We recruited 17 non-smokers and 15 habitual smokers (13 ± 5 pack years). Continuous measurements of mean cerebral blood flow velocity (transcranial Doppler ultrasound), blood pressure (finger photoplethysmography) and heart rate enabled transfer function analysis of the dynamic relationship between pressure and flow (gain, normalised gain, phase and coherence) and baroreflex sensitivity during supine rest before and after smoking a single cigarette (acute smoking).

Results

There were no between-group differences in gain, phase or coherence before acute smoking. However, both groups showed a reduction in gain and coherence, associated with a reduction in baroreflex sensitivity, and increase in phase after acute smoking.

Conclusions

Contrary to our hypothesis, these findings suggest that in the face of a reduction in baroreflex sensitivity acute smoking may potentially improve the ability of the cerebral circulation to buffer against changes in blood pressure. However, chronic smoking did not alter the dynamic relationship between blood pressure and cerebral blood flow velocity. These results have implications on understanding mechanisms for attenuating stroke risk.     

Reduced forearm alpha1-adrenergic vasoconstriction is associated with enhanced heart rate fluctuations in humans.

In the present study, we assessed whether heart rate (HR) or arterial pressure fluctuations are enhanced in healthy young humans with reduced alpha-adrenergic vasoconstrictor responses and, if so, whether this occurs for both alpha1- and alpha2-adrenergic receptor-mediated vasoconstriction. Arterial pressure (brachial artery catheter) and HR (ECG) were monitored continuously, and alpha1- and alpha2-adrenergic responsiveness was determined by assessing the effects of brachial artery infusions of phenylephrine (alpha1-adrenergic agonist) and dexmedetomidine (alpha2-adrenergic agonist), respectively, on forearm blood flow (strain gauge plethysmography). alpha1-Adrenergic responsiveness varied markedly among the subjects (n=20) and was inversely correlated with coefficient of variation for HR (R2=0.37, P<0.01), whereas the responsiveness was not correlated with the coefficient of variation for either systolic or diastolic arterial pressure. alpha1-Adrenergic responsiveness was inversely and more strongly correlated with baroreflex sensitivity (R2=0.62, P<0.0001), determined from beat-to-beat changes in HR and systolic arterial pressure, than the coefficient of variation for HR. On the other hand, alpha2-adrenergic responsiveness was not correlated with any of the parameters determined above. These results suggest that, in healthy young subjects, the enhanced HR response to changes in systolic pressure helps maintain the stability of arterial blood pressure when alpha1-adrenergic responsiveness is reduced.     

Effect of head-down-tilt bed rest and hypovolemia on dynamic regulation of heart rate and blood pressure

Adaptation to head-down-tilt bed rest leads to an apparent abnormality of baroreflex regulation of cardiac period. We hypothesized that this "deconditioning response" could primarily be a result of hypovolemia, rather than a unique adaptation of the autonomic nervous system to bed rest. To test this hypothesis, nine healthy subjects underwent 2 wk of -6 degrees head-down bed rest. One year later, five of these same subjects underwent acute hypovolemia with furosemide to produce the same reductions in plasma volume observed after bed rest. We took advantage of power spectral and transfer function analysis to examine the dynamic relationship between blood pressure (BP) and R-R interval. We found that 1) there were no significant differences between these two interventions with respect to changes in numerous cardiovascular indices, including cardiac filling pressures, arterial pressure, cardiac output, or stroke volume; 2) normalized high-frequency (0.15-0.25 Hz) power of R-R interval variability decreased significantly after both conditions, consistent with similar degrees of vagal withdrawal; 3) transfer function gain (BP to R-R interval), used as an index of arterial-cardiac baroreflex sensitivity, decreased significantly to a similar extent after both conditions in the high-frequency range; the gain also decreased similarly when expressed as BP to heart rate x stroke volume, which provides an index of the ability of the baroreflex to alter BP by modifying systemic flow; and 4) however, the low-frequency (0.05-0.15 Hz) power of systolic BP variability decreased after bed rest (-22%) compared with an increase (+155%) after acute hypovolemia, suggesting a differential response for the regulation of vascular resistance (interaction, P < 0.05). The similarity of changes in the reflex control of the circulation under both conditions is consistent with the hypothesis that reductions in plasma volume may be largely responsible for the observed changes in cardiac baroreflex control after bed rest. However, changes in vasomotor function associated with these two conditions may be different and may suggest a cardiovascular remodeling after bed rest.     

Assessing baroreflex gain from spontaneous variability in conscious dogs: role of causality and respiration

A double exogenous autoregressive (XXAR) causal parametric model was used to estimate the baroreflex gain (alpha(XXAR)) from spontaneous R-R interval and systolic arterial pressure (SAP) variabilities in conscious dogs. This model takes into account 1) effects of current and past SAP variations on the R-R interval (i.e., baroreflex-mediated influences), 2) specific perturbations affecting R-R interval independently of baroreflex circuit (e.g., rhythmic neural inputs modulating R-R interval independently of SAP at frequencies slower than respiration), and 3) influences of respiration-related sources acting independently of baroreflex pathway (e.g., rhythmic neural inputs modulating R-R interval independently of SAP at respiratory rate, including the effect of stimulation of low-pressure receptors). Under control conditions, alpha(XXAR) = 14.7 +/- 7.2 ms/mmHg. It decreases after nitroglycerine infusion and coronary artery occlusion, even though the decrease is significant only after nitroglycerine, and it is completely abolished by total arterial baroreceptor denervation. Moreover, alpha(XXAR) is comparable to or significantly smaller than (depending on the experimental condition) the baroreflex gains derived from sequence, power spectrum [at low frequency (LF) and high frequency (HF)], and cross-spectrum (at LF and HF) analyses and from less complex causal parametric models, thus demonstrating that simpler estimates may be biased by the contemporaneous presence of regulatory mechanisms other than baroreflex mechanisms.     

Adrenergic response of splanchnic arteries from cirrhotic patients: role of nitric oxide, prostanoids, and reactive oxygen species

Peripheral and splanchnic vasodilatation in cirrhotic patients has been related to hyporesponsiveness to vasoconstrictors, but studies to examine the vascular adrenergic response provide contradictory results. Hepatic arteries from cirrhotic patients undergoing liver transplantation and mesenteric arteries from liver donors were obtained. Segments 3 mm long from these arteries were mounted in organ baths for testing isometric adrenergic response. The concentration-dependent contraction to noradrenaline (10(-8) to 10(-4) M) was similar in hepatic and mesenteric arteries, and prazosin (alpha 1-adrenergic antagonist, 10(-6) M), but not yohimbine (alpha 2-adrenergic antagonist, 10(-6) M), produced a rightward parallel displacement of this contraction in both types of arteries. Phenylephrine (alpha 1-adrenergic agonist, 10(-8) to 10(-4) M) and clonidine (alpha 2-adrenergic agonist, 10(-8) to 10(-4) M) also produced concentration-dependent contractions that were comparable in hepatic and mesenteric arteries. The inhibitor of cyclooxygenase meclofenamate (10(-5) M), but not the inhibitor of nitric oxide synthesis N(w)-nitro-l-arginine methyl ester (l-NAME, 10(-4) M), potentiated the response to noradrenaline in hepatic arteries; neither inhibitor affected the response to noradrenaline in mesenteric arteries. Diphenyleneiodonium (DPI; 5 x 10(-6) M), but neither catalase (1000 U/ml) nor tiron (10(-4) M), decreased the maximal contraction for noradrenaline similarly in hepatic and mesenteric arteries. Therefore, it is suggested that, in splanchnic arteries from cirrhotic patients, the adrenergic response and the relative contribution of alpha 1- and alpha 2-adrenoceptors in this response is preserved, and prostanoids, but not nitric oxide, may blunt that response. Products dependent on NAD(P)H oxidase might contribute to the adrenergic response in splanchnic arteries from control and cirrhotic patients.     

Time course analysis of baroreflex sensitivity during postural stress

Postural stress requires immediate autonomic nervous action to maintain blood pressure. We determined time-domain cardiac baroreflex sensitivity (BRS) and time delay (tau) between systolic blood pressure and interbeat interval variations during stepwise changes in the angle of vertical body axis (alpha). The assumption was that with increasing postural stress, BRS becomes attenuated, accompanied by a shift in tau toward higher values. In 10 healthy young volunteers, alpha included 20 degrees head-down tilt (-20 degrees), supine (0 degree), 30 and 70 degrees head-up tilt (30 degrees, 70 degrees), and free standing (90 degrees). Noninvasive blood pressures were analyzed over 6-min periods before and after each change in alpha. The BRS was determined by frequency-domain analysis and with xBRS, a cross-correlation time-domain method. On average, between 28 (-20 degrees) to 45 (90 degrees) xBRS estimates per minute became available. Following a change in alpha, xBRS reached a different mean level in the first minute in 78% of the cases and in 93% after 6 min. With increasing alpha, BRS decreased: BRS = -10.1.sin(alpha) + 18.7 (r(2) = 0.99) with tight correlation between xBRS and cross-spectral gain (r(2) approximately 0.97). Delay tau shifted toward higher values. In conclusion, in healthy subjects the sensitivity of the cardiac baroreflex obtained from time domain decreases linearly with sin(alpha), and the start of baroreflex adaptation to a physiological perturbation like postural stress occurs rapidly. The decreases of BRS and reduction of short tau may be the result of reduced vagal activity with increasing alpha.     

Renal SNA as the primary mediator of slow oscillations in blood pressure during hemorrhage

Blood pressure contains a distinct low-frequency oscillation often termed the Mayer wave. This oscillation is caused by the action of the sympathetic nervous system on the vasculature and results from time delays in the baroreflex feedback loop for the control of sympathetic nerve activity (SNA) in response to changes in blood pressure. In this study, we used bilateral renal denervation to test the hypothesis that it is SNA to the kidney that contributes a large portion of the vascular resistance associated with changes in the strength of the slow oscillation in blood pressure. In conscious rabbits, SNA and blood pressure were measured during hemorrhage (blood withdrawal at 1.35 ml. min(-1). kg(-1) for 20 min). Spectral analysis identified a strong increase in power at 0.3 Hz in SNA and blood pressure in the initial compensatory phase of hemorrhage before blood pressure started to fall. However, in a separate group of renal denervated rabbits, although the power of the 0.3-Hz oscillation under control conditions in blood pressure was similar, it was not altered during hemorrhage. Wavelet analysis revealed the development of low-frequency oscillations at 0.1 Hz in both intact and denervated animals. In conclusion, we propose that changes in the strength of the oscillation at 0.3 Hz in arterial pressure during hemorrhage are primarily mediated by sympathetic activity directed to the kidney.     

Baroreflex sensitivity, blood pressure buffering, and resonance: what are the links? Computer simulation of healthy subjects and heart failure patients.

The arterial baroreflex buffers slow (<0.05 Hz) blood pressure (BP) fluctuations, mainly by controlling peripheral resistance. Baroreflex sensitivity (BRS), an important characteristic of baroreflex control, is often noninvasively assessed by relating heart rate (HR) fluctuations to BP fluctuations; more specifically, spectral BRS assessment techniques focus on the BP-to-HR transfer function around 0.1 Hz. Skepticism about the relevance of BRS to characterize baroreflex-mediated BP buffering is based on two considerations: 1) baroreflex-modulated peripheral vasomotor function is not necessarily related to baroreflex-HR transfer; and 2) although BP fluctuations around 0.1 Hz (Mayer waves) might be related to baroreflex BP buffering, they are merely a not-intended side effect of a closed-loop control system. To further investigate the relationship between BRS and baroreflex-mediated BP buffering, we set up a computer model of baroreflex BP control to simulate normal subjects and heart failure patients. Output variables for various randomly chosen combinations of feedback gains in the baroreflex arms were BP resonance, BP-buffering capacity, and BRS. Our results show that BP buffering and BP resonance are related expressions of baroreflex BP control and depend strongly on the sympathetic gain to the peripheral resistance. BRS is almost uniquely determined by the vagal baroreflex gain to the sinus node. In conclusion, BP buffering and BRS are unrelated unless coupled gains in all baroreflex limbs are assumed. Hence, the clinical benefit of a high BRS is most likely to be attributed to vagal effects on the heart instead of to effective BP buffering.     

Transfer function analysis between arterial pressure and renal sympathetic nerve activity at cardiac pacing frequencies in the rat.

This study examined the possible influence of changes in heart rate (HR) on the gain of the transfer function relating renal sympathetic nerve activity (RSNA) to arterial pressure (AP) at HR frequency in rats. In seven urethane-anesthetized rats, AP and RSNA were recorded under baseline conditions (spontaneous HR = 338 +/- 6 beats/min, i.e., 5.6 +/- 0.1 Hz) and during 70-s periods of cardiac pacing at 6-9 Hz applied in random order. Cardiac pacing slightly increased mean AP (0.8 +/- 0.2 mmHg/Hz) and decreased pulse pressure (-3.6 +/- 0.3 mmHg/Hz) while leaving the mean level of RSNA essentially unaltered (P = 0.680, repeated-measures ANOVA). The gain of the transfer function from AP to RSNA measured at HR frequency was always associated with a strong, significant coherence and was stable between 6 and 9 Hz (P = 0.185). The transfer function gain measured under baseline conditions [2.44 +/- 0.28 normalized units (NU)/mmHg] did not differ from that measured during cardiac pacing (2.46 +/- 0.27 NU/mmHg). On the contrary, phase decreased linearly as a function of HR, which indicated the presence of a fixed time delay (97 +/- 6 ms) between AP and RSNA. In conclusion, the dynamic properties of arterial baroreflex pathways do not affect the gain of the transfer function between AP and RSNA measured at HR frequency in the upper part of the physiological range of HR variations in the rat.     

Causal linear parametric model for baroreflex gain assessment in patients with recent myocardial infarction

Spectral and cross-spectral analysis of R-R interval and systolic arterial pressure (SAP) spontaneous fluctuations have been proposed for noninvasive evaluation of baroreflex sensitivity (BRS). However, results are not in good agreement with clinical measurements. In this study, a bivariate parametric autoregressive model with exogenous input (ARXAR model), able to divide the R-R variability into SAP-related and -unrelated parts, was used to quantify the gain (alpha(ARXAR)) of the baroreflex regulatory mechanism. For performance assessing, two traditional noninvasive methods based on frequency domain analysis [spectral, baroreflex gain by autogressive model (alpha(AR)); cross-spectral, baroreflex gain by bivariate autoregressive model (alpha(2AR))] and one based on the time domain [baroreflex gain by sequence analysis (alpha(SEQ))] were considered and compared with the baroreflex gain by phenylephrine test (alpha(PHE)). The BRS evaluation was performed on 30 patients (61 +/- 10 yr) with recent (10 +/- 3 days) myocardial infarction. The ARXAR model allowed dividing the R-R variability (950 +/- 1,099 ms(2)) into SAP-related (256 +/- 418 ms(2)) and SAP-unrelated (694 +/- 728 ms(2)) parts. alpha(AR) (12.2 +/- 6.1 ms/mmHg) and alpha(2AR) (8.9 +/- 5.6 ms/mmHg) as well as alpha(SEQ) (12.6 +/- 7.1 ms/mmHg) overestimated BRS assessed by alpha(PHE) (6.4 +/- 4.7 ms/mmHg), whereas the ARXAR index gave a comparable value (alpha(ARXAR) = 5.4 +/- 3.3 ms/mmHg). All noninvasive methods were significantly correlated to alpha(PHE) (alpha(ARXAR) and alpha(SEQ) were more correlated than the other indexes). Thus the baroreflex gain obtained describing the causal dependence of R-R interval on SAP showed a good agreement with alpha(PHE) and may provide additional information regarding the gain estimation in the frequency domain.     

A derivative-sigmoidal model reproduces operating point-dependent baroreflex neural arc transfer characteristics

A cascade model comprised of a derivative filter followed by a nonlinear sigmoidal component reproduces the input size dependence of transfer gain in the baroreflex neural arc from baroreceptor pressure input to efferent sympathetic nerve activity (SNA). We examined whether the same model could predict the operating point dependence of the baroreflex neural arc transfer characteristics estimated by a binary white noise input. In eight anesthetized rabbits, we isolated bilateral carotid sinuses from the systemic circulation and controlled intracarotid sinus pressure (CSP). We estimated the linear transfer function from CSP to SNA while varying mean CSP among 70, 100, 130, and 160 mmHg (P(70), P(100), P(130), and P(160), respectively). The transfer gain at 0.01 Hz was significantly smaller at P(70) (0.61 +/- 0.26) and P(160) (0.60 +/- 0.25) than at P(100) (1.32 +/- 0.42) and P(130) (1.36 +/- 0.45) (in arbitrary units/mmHg; means +/- SD; P < 0.05). In contrast, transfer gain values above 0.5 Hz were similar among the protocols. As a result, the slope of increasing gain between 0.1 and 0.5 Hz was significantly steeper at P(70) (17.6 +/- 3.6) and P(160) (14.1 +/- 4.3) than at P(100) (8.1 +/- 4.4) and P(130) (7.4 +/- 6.6) (in dB/decade; means +/- SD; P < 0.05). These results were consistent with those predicted by the derivative-sigmoidal model, where the deviation of mean input pressure from the center of the sigmoidal nonlinearity reduced the transfer gain mainly in the low-frequency range. The derivative-sigmoidal model functionally reproduces the dynamic SNA regulation by the arterial baroreflex over a wide operating range.     

Estimation of the total peripheral resistance baroreflex impulse response from spontaneous hemodynamic variability

We previously developed a mathematical analysis technique for estimating the static gain values of the arterial total peripheral resistance (TPR) baroreflex (G(A)) and the cardiopulmonary TPR baroreflex (G(C)) from small, spontaneous beat-to-beat fluctuations in arterial blood pressure, cardiac output, and stroke volume. Here, we extended the mathematical analysis so as to also estimate the entire arterial TPR baroreflex impulse response [h(A)(t)] as well as the lumped arterial compliance (AC). The extended technique may therefore provide a linear dynamic characterization of TPR baroreflex systems during normal physiological conditions from potentially noninvasive measurements. We theoretically evaluated the technique with respect to realistic spontaneous hemodynamic variability generated by a cardiovascular simulator with known system properties. Our results showed that the technique reliably estimated h(A)(t) [error = 30.2 +/- 2.6% for the square root of energy (E(A)), 19.7 +/- 1.6% for absolute peak amplitude (P(A)), 37.3 +/- 2.5% for G(A), and 33.1 +/- 4.9% for the overall time constant] and AC (error = 17.6 +/- 4.2%) under various simulator parameter values and reliably tracked changes in G(C). We also experimentally evaluated the technique with respect to spontaneous hemodynamic variability measured from seven conscious dogs before and after chronic arterial baroreceptor denervation. Our results showed that the technique correctly predicted the abolishment of h(A)(t) [E(A) = 1.0 +/- 0.2 to 0.3 +/- 0.1, P(A) = 0.3 +/- 0.1 to 0.1 +/- 0.0 s(-1), and G(A) = -2.1 +/- 0.6 to 0.3 +/- 0.2 (P < 0.05)] and the enhancement of G(C) [-0.7 +/- 0.44 to -1.8 +/- 0.2 (P < 0.05)] following the chronic intervention. Moreover, the technique yielded estimates whose values were consistent with those reported with more invasive and/or experimentally difficult methods.