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.     

Cardiovascular responses to hypoxia and hypercapnia in barodenervated rats

Experiments were performed to examine the role of the arterial baroreceptors in the cardiovascular responses to acute hypoxia and hypercapnia in conscious rats chronically instrumented to monitor systemic hemodynamics. One group of rats remained intact, whereas a second group was barodenervated. Both groups of rats retained arterial chemoreceptive function as demonstrated by augmented ventilation in response to hypoxia. The cardiovascular effects to varying inspired levels of O2 and CO2 were examined and compared between intact and barodenervated rats. No differences between groups were noted in response to mild hypercapnia (5% CO2); however, the bradycardia and reduction in cardiac output observed in intact rats breathing 10% CO2 were eliminated by barodenervation. In addition, hypocapnic hypoxia caused a marked fall in blood pressure and total peripheral resistance (TPR) in barodenervated rats compared with controls. Similar differences in TPR were observed between the groups in response to isocapnic and hypercapnic hypoxia as well. It is concluded that the arterial baroreflex is an important component of the overall cardiovascular responses to both hypercapnic and hypoxic stimuli in the conscious rat.     

Test of dynamic closed-loop baroreflex and autoregulatory control of total peripheral resistance in intact and conscious sheep

This is the first study able to examine and delineate the actual actions of the physiological mechanisms responsible for the dynamic couplings between cardiac output (CO), arterial pressure (Pa), right atrial pressure (PRA), and total peripheral resistance (TPR) in an individual subject without altering the underlying regulatory mechanisms. Eight conscious male sheep were used, where both types of baroreceptors were independently exposed to simultaneous beat-to-beat pressure perturbations under intact closed-loop conditions while CO, Pa, PRA, and TPR were measured. We applied the cardiovascular system identification method proposed in a companion paper (4) to quantitatively characterize the dynamic closed-loop transfer relations CO-->Pa, PRA-->Pa, Pa-->TPR, and PRA-->TPR from the measured signals. To validate the dynamic properties of the estimated transfer relations, the essential parts of the linear dynamics of the model were independently and comprehensively evaluated via error model cross-validation, and the overall model's steady-state behavior was compared with a separate random effects regression approach. In addition to numerous physiological findings, we found that the cardiovascular system identification results were exceptionally consistent with the analytically derived solutions previously discussed in Ref. 4. In conclusion, this study presents the first time validation of a cardiovascular system identification method by means of experimentally acquired animal data in the intact and conscious animal and offers a set of powerful quantitative tools essential to advancing our knowledge of cardiovascular regulatory physiology.     

Clinical value of baroreflex sensitivity

The arterial baroreflex is an important determinant of the neural regulation of the cardiovascular system. It has been recognised that baroreflex-mediated sympathoexcitation contributes to the development and progression of many cardiovascular disorders. Accordingly, the quantitative estimation of the arterial baroreceptor-heart rate reflex (baroreflex sensitivity, BRS), has been regarded as a synthetic index of neural regulation at the sinus atrial node. The evaluation of BRS has been shown to provide clinical and prognostic information in a variety of cardiovascular diseases, including myocardial infarction and heart failure that are reviewed in the present article.     

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.     

Theoretical considerations in the dynamic closed-loop baroreflex and autoregulatory control of total peripheral resistance

The most important goal of this study is to enhance our understanding of the crucial functional relationships that determine the behavior of the systemic circulation and its underlying physiological regulatory mechanisms with minimal modeling. To the present day, much has been said about the indirect hydraulic effects of right atrial pressure (PRA) via cardiac output (CO) on arterial pressure (Pa) through the heart and pulmonary circulation or the direct regulatory effects of PRA on Pa through the cardiopulmonary baroreflex; however, very little attention has been given to the hydraulic influence that PRA exerts directly through the systemic circulation. The experimental data reported by Guyton et al. in 1957 demonstrated that steady-state PRA and the rate at which blood passes through the systemic circulation are locked in a functional relationship independent of any consequence of altered PRA on cardiac function. With this in mind, we emphasize the analytic algebraic analysis of the systemic circulation composed of arteries, veins, and its underlying physiological regulatory mechanisms of baroreflex and autoregulatory modulation of total peripheral resistance (TPR), where the behavior of the system can be analytically synthesized from an understanding of its minimal elements. As a result of this analysis, we present a novel mathematical method to determine short-term TPR fluctuations, which accounts for the entirety of observed Pa fluctuations, and propose a new cardiovascular system identification method to delineate the actual actions of the physiological mechanisms responsible for the dynamic couplings between CO, Pa, PRA, and TPR in an individual subject.     

What is the ultimate goal in neural regulation of cardiovascular function?

We used the following multiple-choice question after a series of lectures in cardiovascular physiology in the first year of an undergraduate medical curriculum (n = 66) to assess whether students had understood the neural regulation of cardiovascular function. In health, neural cardiovascular mechanisms are geared toward maintaining A) cardiac output, B) total peripheral resistance (TPR), C) arterial blood pressure (BP), D) tissue blood flow. The same question was administered to 275 graduates preparing for postgraduate exams (but not following the same series of lectures as the undergraduates). In both groups, we found a large proportion of incorrect answers (70% in undergraduates and 85% in graduates) and sorted this out by offering a step-by-step explanation and two examples and found it successful: 1) What happens to BP and heart rate (HR) when a person loses 500 ml of blood ( approximately 10% of blood volume) in one minute? 2) What happens to your BP and HR as you get out of bed after a night's sleep? Flow = perfusion pressure/resistance to flow; cardiac output = BP/TPR; BP = cardiac output x TPR = [stroke volume (SV) x HR] x TPR. In both examples, BP decreases and is rapidly brought into the normal range by the arterial baroreflex mechanism. TBF is regulated chiefly by varying local vascular resistance (autoregulation). In summary, the ultimate goal of all neural cardiovascular reflex mechanisms is to maintain arterial BP within a range in which tissues can regulate their own blood flows. Cardiovascular control during exercise was used as an example to emphasize these facts. A discussion of this kind triggered interest in the minds of students and graduates, helping them get rid of a major misconception in about 20-40 minutes.     

A Reproducible Computerized Method for Quantitation of Capillary Density using Nailfold Capillaroscopy

Capillaroscopy is a non-invasive, efficient, relatively inexpensive and easy to learn methodology for directly visualizing the microcirculation. The capillaroscopy technique can provide insight into a patient’s microvascular health, leading to a variety of potentially valuable dermatologic, ophthalmologic, rheumatologic and cardiovascular clinical applications. In addition, tumor growth may be dependent on angiogenesis, which can be quantitated by measuring microvessel density within the tumor. However, there is currently little to no standardization of techniques, and only one publication to date reports the reliability of a currently available, complex computer based algorithms for quantitating capillaroscopy data.¹ This paper describes a new, simpler, reliable, standardized capillary counting algorithm for quantitating nailfold capillaroscopy data. A simple, reproducible computerized capillaroscopy algorithm such as this would facilitate more widespread use of the technique among researchers and clinicians. Many researchers currently analyze capillaroscopy images by hand, promoting user fatigue and subjectivity of the results. This paper describes a novel, easy-to-use automated image processing algorithm in addition to a reproducible, semi-automated counting algorithm. This algorithm enables analysis of images in minutes while reducing subjectivity; only a minimal amount of training time (in our experience, less than 1 hr) is needed to learn the technique.     

Angiotensin restores atrial natriuretic factor-induced decrease of baroreceptor sensitivity in normotensive rats, but not in spontaneously hypertensive rats

The effect of atrial natriuretic factor (ANF) on baroreflex sensitivity was determined in unanesthetized normotensive (Wistar-Kyoto, WKY) or spontaneously hypertensive rats (SHR) during acute hypertensive stimuli (phenylephrine) or hypotensive stimuli (sodium nitroprusside). The i.v. dose of rat ANF [( Ser99,Tyr126]ANF) was 50 ng/min per rat, sufficient to decrease mean arterial blood pressure (ABP) by about 6 mmHg (1 mmHg = 133.3 Pa) in WKY. SHR showed no change in ABP with this ANF dose. During a control infusion of physiological saline, the mean heart rate (HR) response to increases in ABP was -1.30 +/- 0.27 beats/min (bpm)/mmHg in WKY and -0.37 +/- 0.22 in SHR (p less than 0.05). These values were not affected significantly by ANF. However, ANF blunted chronotropic responses to ABP decreases. The control values of the delta HR/delta ABP slope in WKY and SHR were -2.34 +/- 0.57 and -2.01 +/- 0.37 bpm/mmHg, respectively. In the presence of ANF, the slope changed to -0.36 +/- 0.43 (i.e., bradycardia in response to hypotension) in WKY and to +0.20 +/- 0.21 in SHR (p less than 0.005 for the difference from control for both). This ANF-induced loss of baroreflex sensitivity was reversed in WKY by the addition of angiotensin I (sufficient to increase ABP by 5 mmHg in control rats). Angiotensin did not restore baroreflex sensitivity in ANF-infused SHR, and ANF had no effect on the ABP increase caused by angiotensin in either group. The data suggest that ANF does not act on baroreceptor structures directly, but inhibits mechanisms involved in efferent sympathetic activation. Parasympathetic responses do not appear to be compromised.     

Estimation of changes in instantaneous aortic blood flow by the analysis of arterial blood pressure

The purpose of this study was to introduce and validate a new algorithm to estimate instantaneous aortic blood flow (ABF) by mathematical analysis of arterial blood pressure (ABP) waveforms. The algorithm is based on an autoregressive with exogenous input (ARX) model. We applied this algorithm to diastolic ABP waveforms to estimate the autoregressive model coefficients by requiring the estimated diastolic flow to be zero. The algorithm incorporating the coefficients was then applied to the entire ABP signal to estimate ABF. The algorithm was applied to six Yorkshire swine data sets over a wide range of physiological conditions for validation. Quantitative measures of waveform shape (standard deviation, skewness, and kurtosis), as well as stroke volume and cardiac output from the estimated ABF, were computed. Values of these measures were compared with those obtained from ABF waveforms recorded using a Transonic aortic flow probe placed around the aortic root. The estimation errors were compared with those obtained using a windkessel model. The ARX model algorithm achieved significantly lower errors in the waveform measures, stroke volume, and cardiac output than those obtained using the windkessel model (P < 0.05).     

Dynamic regulation of heart rate during acute hypotension: new insight into baroreflex function

To examine the dynamic properties of baroreflex function, we measured beat-to-beat changes in arterial blood pressure (ABP) and heart rate (HR) during acute hypotension induced by thigh cuff deflation in 10 healthy subjects under supine resting conditions and during progressive lower body negative pressure (LBNP). The quantitative, temporal relationship between ABP and HR was fitted by a second-order autoregressive (AR) model. The frequency response was evaluated by transfer function analysis. Results: HR changes during acute hypotension appear to be controlled by an ABP error signal between baseline and induced hypotension. The quantitative relationship between changes in ABP and HR is characterized by a second-order AR model with a pure time delay of 0.75 s containing low-pass filter properties. During LBNP, the change in HR/change in ABP during induced hypotension significantly decreased, as did the numerator coefficients of the AR model and transfer function gain. Conclusions: 1) Beat-to-beat HR responses to dynamic changes in ABP may be controlled by an error signal rather than directional changes in pressure, suggesting a "set point" mechanism in short-term ABP control. 2) The quantitative relationship between dynamic changes in ABP and HR can be described by a second-order AR model with a pure time delay. 3) The ability of the baroreflex to evoke a HR response to transient changes in pressure was reduced during LBNP, which was due primarily to a reduction of the static gain of the baroreflex.     

家兔Bezold—Jarisch反射的血流动力学效应

在40只麻醉兔,观察经冠脉内注射尼古丁诱发Bezold-Jarisch反射时的血流动力学变化。反射效应表现为心率减慢、动脉血压和左心室收缩压降低以及左心室内压微分值减小。切断两侧窦神经和减压神经后,上述效应增强;两侧迷走神经切断后,多数动物反射效应消失。 冠脉内注射尼古丁后,心输出量和总外周阻力均下降。人工起搏心脏以防止心率减慢时,对上述效应无明显影响。动物阿托品化并切除两侧星状神经节后,心率减慢基本消失,但动脉血压降低的程度并无明显变化。结果提示,Bezold-Jarisch反射时所表现的动脉血压降低,可归因于心输出量减少和总外周阻力降低,而以后者为主。     

Chronic hypertension in ANP knockout mice: contribution of peripheral resistance

Atrial Natriuretic Peptide (ANP) exerts a chronic hypotensive effect which is mediated by a reduction in total peripheral resistance (TPR). Mice with a homozygous disruption of the pro-ANP gene (-/-) fail to synthesize ANP and develop chronic hypertension in comparison to their normotensive wild-type (+/+) siblings. In order to determine whether alterations in basal hemodynamics underlie the hypertension associated with lack of endogenous ANP activity, we used anesthetized mice to measure arterial blood pressure (ABP) and heart rate (HR), as well as cardiac output (CO) by thermodilution technique. -/- (n = 7) and +/+ (n = 10) mice of comparable weight and age were used. Stroke volume (SV) and TPR were derived from CO, HR, and ABP by a standard formula. ABP (mm Hg) was significantly higher in -/- (132+/-4) (P < 0.0001) than in +/+ mice (95+/-2). CO (ml min(-1)), HR(beats min(-1))and SV (microl beat(-1)) did not differ significantly between -/- and +/+ mice (CO -/- = 7.3+/-0.5, +/+ = 8.3+/-0.6; HR -/- = 407+/-22, +/+ = 462+/-21; SV -/- = 17.6+/-1.1, +/+ = 17.6+/-1.7). However, TPR (mm Hg ml(-1) min(-1)) was significantly elevated in -/- mice (18.4+/-0.7) compared to +/+ mice (12.3+/-1) (P = 0.0003). Autonomic ganglion blockade with a mixture of hexamethonium and pentolinium was followed by comparable percent reductions in CO (-/- = 28+/-4, +/+ = 29+/-3), HR (-/- = 9+/-4, +/+ = 16+/-4) and SV(-/- = 21+/-4, +/+ = 15+/-6) in both genotypes. However, the concomitant decrease in ABP (%) in -/- (41+/-2) was significantly greater than in +/+ (23+/-4) mice (P = 0.0009) and was accompanied by a significant reduction in TPR. We conclude that the hypertension associated with lack of endogenous ANP is due to elevated TPR, which is determined by an increase in cardiovascular autonomic tone.     

Limitations of Stroke Volume Estimation by Non-Invasive Blood Pressure Monitoring in Hypergravity

Background

Altitude and gravity changes during aeromedical evacuations induce exacerbated cardiovascular responses in unstable patients. Non-invasive cardiac output monitoring is difficult to perform in this environment with limited access to the patient. We evaluated the feasibility and accuracy of stroke volume estimation by finger photoplethysmography (SVp) in hypergravity.

Methods

Finger arterial blood pressure (ABP) waveforms were recorded continuously in ten healthy subjects before, during and after exposure to +Gz accelerations in a human centrifuge. The protocol consisted of a 2-min and 8-min exposure up to +4 Gz. SVp was computed from ABP using Liljestrand, systolic area, and Windkessel algorithms, and compared with reference values measured by echocardiography (SVe) before and after the centrifuge runs.

Results

The ABP signal could be used in 83.3% of cases. After calibration with echocardiography, SVp changes did not differ from SVe and values were linearly correlated (p<0.001). The three algorithms gave comparable SVp. Reproducibility between SVp and SVe was the best with the systolic area algorithm (limits of agreement −20.5 and +38.3 ml).

Conclusions

Non-invasive ABP photoplethysmographic monitoring is an interesting technique to estimate relative stroke volume changes in moderate and sustained hypergravity. This method may aid physicians for aeronautic patient monitoring.     

Cardiovascular Complications following Chronic Treatment with Cocaine and Testosterone in Adolescent Rats

Concomitant use of anabolic androgenic steroids and cocaine has increased in the last years. However, the effects of chronic exposure to these substances during adolescence on cardiovascular function are unknown. Here, we investigated the effects of treatment for 10 consecutive days with testosterone and cocaine alone or in combination on basal cardiovascular parameters, baroreflex activity, hemodynamic responses to vasoactive agents, and cardiac morphology in adolescent rats. Administration of testosterone alone increased arterial pressure, reduced heart rate (HR), and exacerbated the tachycardiac baroreflex response. Cocaine-treated animals showed resting bradycardia without changes in arterial pressure and baroreflex activity. Combined treatment with testosterone and cocaine did not affect baseline arterial pressure and HR, but reduced baroreflex-mediated tachycardia. None of the treatments affected arterial pressure response to either vasoconstrictor or vasodilator agents. Also, heart to body ratio and left and right ventricular wall thickness were not modified by drug treatments. However, histological analysis of left ventricular sections of animals subjected to treatment with testosterone and cocaine alone and combined showed a greater spacing between cardiac muscle fibers, dilated blood vessels, and fibrosis. These data show important cardiovascular changes following treatment with testosterone in adolescent rats. However, the results suggest that exposure to cocaine alone or combined with testosterone during adolescence minimally affect cardiovascular function.     

Intermittent hypobaric hypoxia exposure does not cause sustained alterations in autonomic control of blood pressure in young athletes

Intermittent hypoxia (IH), which refers to the discontinuous use of hypoxia to reproduce some key features of altitude acclimatization, is commonly used in athletes to improve their performance. However, variations of IH are also used as a model for sleep apnea, causing sustained sympathoexcitation and hypertension in animals and, thus, raising concerns over the safety of this model. We tested the hypothesis that chronic IH at rest alters autonomic control of arterial pressure in healthy trained individuals. Twenty-two young athletes (11 men and 11 women) were randomly assigned to hypobaric hypoxia (simulated altitude of 4,000-5,500 m) or normoxia (500 m) in a double-blind and placebo-controlled design. Both groups rested in a hypobaric chamber for 3 h/day, 5 days/wk for 4 wk. In the sitting position, resting hemodynamics, including heart rate (HR), blood pressure (BP), cardiac output (Q(c), C(2)H(2) rebreathing), stroke volume (SV = Q(c)/HR), and total peripheral resistance (TPR = mean BP/Q(c)), were measured, dynamic cardiovascular regulation was assessed by spectral and transfer function analysis of cardiovascular variability, and cardiac-vagal baroreflex function was evaluated by a Valsalva maneuver, twice before and 3 days after the last chamber exposure. We found no significant differences in HR, BP, Q(c), SV, TPR, cardiovascular variability, or cardiac-vagal baroreflex function between the groups at any time. These results suggest that exposure to intermittent hypobaric hypoxia for 4 wk does not cause sustained alterations in autonomic control of BP in young athletes. In contrast to animal studies, we found no secondary evidence for sustained physiologically significant sympathoexcitation in this model.     

Pulse pressure variation tracking using sequential Monte Carlo methods

The pulse pressure variation (PPV) is a measure of the respiratory effect on the variation of systemic arterial blood pressure (ABP) in patients receiving full mechanical ventilation. It is a promising predictor of increases in cardiac output due to an infusion of fluid. We describe a novel automatic algorithm to estimate the PPV of ABP signals recorded under full respiratory support. The algorithm utilizes our recently developed sequential Monte Carlo method (SMCM), which is called a maximum a-posteriori adaptive marginalized particle filter (MAM-PF). MAM-PF estimates the state-space model parameters of the ABP signal continuously and its upper and lower envelopes are derived as a combination of those parameter estimates. Then, the continuous PPV values can be easily obtained based on those estimated envelopes. We report the assessment results of the proposed algorithm on real ABP signals.     

Repetitive apneas reduce nonlinear dynamical complexity of the human cardiovascular control system.

We tested the hypothesis that intermittent apneas performed by awake subjects simulate obstructive sleep apnea (OSA) and change dynamic complexity of the cardiovascular control system by repetitive short time stimulation of arterial chemoreceptors. Correlation dimension (CD) and reccurent plot quantification calculated as ratio % determinism versus % recurrence (RDR) were used.as indices of chaotic dynamics. Thirty three normotensive subjects of mean age 21,58 +/- 4,1 performed 10 voluntary apneas 1 min. each separated by 1 min free breathing period. Systolic (SYS), diastolic (DIAS) arterial blood pressure was continuously recorded by finger volume clamp. Stroke volume (SV) was estimated by pulse pressure analysis. Cardiac output (CO) and total peripheral resistance (TPR) were calculated by Portapress system. Cardiac inter-beat interval (IBI) was measured from R-R intervals of ECG. Standard deviation (SD), an index of linear variability, was calculated in 1 min epoch. Dynamics of cardiovascular variables was computed in each subject during 20 min. rest (C), 20 min. of 10 apneas, 1 min each, separated by 1 min free breathing (A), and in 20 min. recovery free breathing (R). In A period CD of all circulatory variables was significantly reduced and RDR augmented. In 23 out of 33 subjects decreased nonlinear dynamics of TPR was carried over from A to R. In contrast, SD increased significantly in A. In conclusion, intermittent brief chemoreflex stimulations by repetitive apneas increase blood pressure and TPR and decrease chaotic behaviour and complexity of the cardiovascular autonomic control system, presumably by inhibition of some regulatory loops such as baroreflex, less vital for survival at oxygen deprivation. Reduced complexity could be implicated in the mechanism of arterial hypertension linked with OSA.     

Chronic intermittent hypoxia impairs baroreflex control of heart rate but enhances heart rate responses to vagal efferent stimulation in anesthetized mice

Chronic intermittent hypoxia (CIH) leads to increased sympathetic nerve activity and arterial hypertension. In this study, we tested the hypothesis that CIH impairs baroreflex (BR) control of heart rate (HR) in mice, and that decreased cardiac chronotropic responsiveness to vagal efferent activity contributes to such impairment. C57BL/6J mice were exposed to either room air (RA) or CIH (6-min alternations of 21% O(2) and 5.7% O(2), 12 h/day) for 90 days. After the treatment period, mice were anesthetized (Avertin) and arterial blood pressure (ABP) was measured from the femoral artery. Mean ABP (MABP) was significantly increased in mice exposed to CIH (98.7 +/- 2.5 vs. RA: 78.9 +/- 1.4 mmHg, P < 0.001). CIH increased HR significantly (584.7 +/- 8.9 beats/min; RA: 518.2 +/- 17.9 beats/min, P < 0.05). Sustained infusion of phenylephrine (PE) at different doses (0.1-0.4 microg/min) significantly increased MABP in both CIH and RA mice, but the ABP-mediated decreases in HR were significantly attenuated in mice exposed to CIH (P < 0.001). In contrast, decreases in HR in response to electrical stimulation of the left vagus nerve (30 microA, 2-ms pulses) were significantly enhanced in mice exposed to CIH compared with RA mice at low frequencies. We conclude that CIH elicits a sustained impairment of baroreflex control of HR in mice. The blunted BR-mediated bradycardia occurs despite enhanced cardiac chronotropic responsiveness to vagal efferent stimulation. This suggests that an afferent and/or a central defect is responsible for the baroreflex impairment following CIH.     

Baroreceptor reflex control of heart rate in rats studied by induced and autogenic changes in arterial pressure

The function of the arterial baroreflex has traditionally been assessed by measurement of reflex changes in heart rate (HR) or sympathetic nerve activity resulting from experimenter-induced manipulation of arterial blood pressure (the Oxford method, also termed the pharmacological method). However, logistical and flexibility limitations of this technique have promoted the development of new methods for assessing baroreflex function such as the evaluation of changes in spontaneous arterial pressure and HR. Although this new spontaneous method has been validated in dogs and humans, it has not been rigorously tested in rats. In the present study, the method of correlating spontaneous changes in systolic blood pressure and HR was evaluated in resting, normotensive Sprague-Dawley rats. This technique was found to be neither reliable nor valid under the conditions employed in the present protocol. We also tested a variation of the spontaneous method that evaluates particular sequences of data during which arterial pressure and pulse interval are changing in the same direction for at least three consecutive heartbeats (the sequence method). The sequence method did not provide extra reliability or validity over the spontaneous method. We conclude that due to the restricted range of variability obtained by measuring spontaneous blood pressure fluctuations, the spontaneous and sequence techniques do not provide data that are comparable to the traditional method of assessing HR changes triggered by arterial blood pressure increases and decreases induced by vasoactive drugs. However, it is possible that surgical stress obscured the relationship between blood pressure and HR, and therefore additional studies are needed to determine whether the spontaneous and sequence methods can be applied to rats during different behavioral states.