Systems analysis of the carotid sinus baroreflex system using a sum-of-sinusoidal input.

The purpose of the present study was to determine the dynamic characteristics of the carotid sinus baroreflex system (CS) employing systems analysis. In 28 anesthetized and mechanically ventilated dogs with vagotomy, intracarotid sinus pressure (ICSP) was changed artificially. In protocol 1 (n = 7), we estimated the transfer function of the CS by means of a single sinusoidal input (SIN), the Gaussian white-noise input (GWN), and a sum-of-sinusoidal input (SUM). The transfer function of ICSP to systemic arterial pressure (SAP) was second-order delay with an identical corner frequency of 0.025 Hz and damping ratio of 0.7. The steady-state gain estimated using GWN (1.12 +/- 0.13) or SUM (1.13 +/- 0.08) was significantly smaller than SIN (1.69 +/- 0.25). In protocol 2, to find the reason why there was a difference among the estimated steady-state gains, we investigated the effect of ICSP pulsation on the open-loop gain of the CS. The maximum gain of the gain curve was decreased and the operating range was increased significantly with the 2-Hz pulsation. We could simulate the above phenomena by using a model with a nonlinear sigmoidal relationship between ICSP and SAP. The dynamic characteristics of the CS appeared to be changed by pulsation, but this phenomenon was attributable to the sigmoidal nature of the relationship between ICSP and SAP. Pulsation decreases the maximum gain and increases the operating range, which may contribute to stability of the CS and homeostasis of SAP.     

Changes in monoamine content of the rabbit carotid body following prolonged electrical stimulation of the carotid sinus nerve

In the anaesthetized, paralysed and artificially ventilated rabbit the carotid sinus nerve (CSN) has been stimulated electrically for 6 h. At the end of the stimulation period, the carotid body (CB) has been removed, frozen and processed for measurement of the monoamines (MA) and of their catabolites with high-pressure liquid chromatography and electrochemical detection (HPLC-ECD). Results show a significant increase of dopamine (DA) and adrenaline (A) content and of all the metabolites. Besides an important augmentation of DA metabolism suggests that CSN efferent activity exerts some regulation on the MA content and turnover of the CB.     

Time-dependent effect of sectioning carotid sinus nerves on the vagally mediated baroreflex

The purpose of the reported experiments was to examine whether the vagally mediated baroreflex system (V-system) increases its feedback gain with time after sectioning of the carotid sinus nerves (CSN). In 10 dogs anesthetized with Nembutal, we determined the overall open-loop gain (G) of the rapidly acting arterial pressure control system. G was assessed as (AP_I/AP_S)-1, where AP_I and AP_S represent the immediate and steady-state decreases in arterial pressure at the aortic arch following a fast step-wise reduction in blood volume. AP_I, AP_S and G_INTACT in the intact condition (30th min before sectioning of the CSN) were –1.8±0.1 kPa, –0.20±0.01 kPa and 8.4±0.3 (mean±SE), respectively. The mean values of AP_I, AP_S and G after sectioning of the CSN (G_V), first averaged within individual dogs and then averaged for ten dogs, were –2.53±0.07 kPa, –1.1±0.05 kPa, and 1.5±0.1, respectively. G_V did not change with time over about 4 h after sectioning of the CSN. It is concluded that the V-system cannot augment its ability to restore arterial pressure in compensation for the lost function of the carotid sinus baroreflex system over 4 h after sectioning of the CSN in the anesthetized dog.     

Effects of diazepam on the carotid sinus baroreflex control of circulation in rabbits

To examine the effects of diazepam on the carotid sinus baroreflex control of circulation, bilateral carotid occlusion was performed on 14 conscious rabbits with aortic denervation. The responses of mean arterial pressure, heart rate, cardiac output and total peripheral resistance were obtained. The haemodynamic responses to carotid occlusion were evaluated at cumulative doses of 0.5 and 1.0 mg kg-1 of diazepam. The administration of diazepam decreased cardiac output and increased total peripheral resistance significantly, but did not affect the arterial pressure and heart rate. The response of total peripheral resistance to carotid occlusion was significantly increased from 0.118 +/- 0.018 (mean +/- SE) to 0.154 +/- 0.026 mmHg min ml-1 at 1.0 mg kg-1 of diazepam. The heart rate response was attenuated significantly from 41 +/- 5 to 24 +/- 4 beats min-1 at 1.0 mg kg-1 of diazepam. Diazepam did not alter the response of arterial pressure to carotid occlusion. We suggest that the dissociated effects of diazepam on the reflex control of circulation reflect the dissociated influences of diazepam on the central sympathetic and vagal-mediated pathways.     

Open-loop dynamic and static characteristics of the carotid sinus baroreflex in rats with chronic heart failure after myocardial infarction

We estimated open-loop dynamic characteristics of the carotid sinus baroreflex in normal control rats and chronic heart failure (CHF) rats after myocardial infarction. First, the neural arc transfer function from carotid sinus pressure to splanchnic sympathetic nerve activity (SNA) and its corresponding step response were examined. Although the steady-state response was attenuated in CHF, the negative peak response and the time to peak did not change significantly, suggesting preserved neural arc dynamic characteristics. Next, the peripheral arc transfer function from SNA to arterial pressure (AP) and its corresponding step response were examined. The steady-state response and the initial slope were reduced in CHF, suggesting impaired end-organ responses. In a simulation study based on the dynamic and static characteristics, the percent recovery of AP was reduced progressively as the size of disturbance increased in CHF, suggesting that a reserve for AP buffering is lost in CHF despite relatively maintained baseline AP.     

The effect of time of electrical stimulation of the carotid sinus on the amount of reduction in arterial pressure

Summary On narcotised dogs, the carotid sinus nerve was stimulated by means on electrical R-wave-triggered pulse trains when depressor nerves were either intact or cut.The stimulation was begun in the range from 0–210 msec after the R-wave. The effectiveness of pulse trains was determined by the level of reduction in mean arterial pressure.In the time range studied, the level of reduction in pressure versus time of stimulation shows two maxima of reduction at 30 and 90 msec and a plateau from 110–150 msec. Stimuli applied later than 150 msec after the R-wave, display a contnuous reduction in effectiveness.The occurrence of the maxima is considered to be due to a coincidence of the pressor afferences from heart, aortic arch and carotid sinus, arriving at the circulatory centres spaced in time with the electrical stimuli.The times at which the maxima of reduction are found to occur could be significant in programming baropacers.     

The principle of electrical carotid sinus nerve stimulation: A nerve pacemaker system for angina pectoris and hypertension therapy

Electrical carotid sinus nerve stimulation (CSNS) via an implanted electrode receiver assembly, radio frequency coupled to an external signal generator, is an experimental therapy for hypertension and angina pectoris. CSNS increases afferent information to the central nervous system exerting neurally regulated decreases in heart rate, stroke volume, and blood pressure. No nonspecific side effects are observed, in contrast to drug therapy. A nerve pacemaker system is described and compared to the commonly used open-loop stimulator system (fixed frequency and intensity CSNS). It is a closed-loop system, controlled by heart rate (as an indicator of the state of “arousal” and of sympathetic activity) and, thereby, feedback-controlled by its therapeutic effects. The miniaturized (hybrid technology) system consists of an ECG amplifier, a stimulus pattern memory with I-O periphery and a transmitter, including an antenna coil to be coupled to the implanted assembly. Stimulus parameters (frequency and amplitude of impulses) are optimized for each patient individually. Stimulus patterns (pulse synchronous amplitude modulated groups of impulses) are adapted to the patient's cardiovascular situation. The nerve pacemaker may be an alternative to drug therapy or major surgery in both diseases. Compatible with the open-loop system, it replaces the first step in previously treated CSNS patients. Clinical application was possible through cooperation with the Department of Cardiology, Medical Clinic, Bonn University, Bonn, Germany, FRG (Prof. Schaede, Prof. Simon and Dr. Schilling). The miniaturized (hybrid technology) version of the nerve pacemaker was realized through cooperation with the Berlin Technical University (W. George). Parts of this work were sponsored by Stiftung Volkswagenwerk and Deutsche Forschungsgemeinschaft.     

Closed-loop control of the heart rate by electrical stimulation of the vagus nerve

Stimulation of the vagus nerve potentially decreases the risk of sudden cardiac death. An improvement of the technique would be its regulation using the heart rate (HR) as a feedback variable. We address the possibility of closed-loop control of the HR, focusing on the stimulation parameters, nerve fibre populations and the reproducibility of the cardiovascular response. The response to electrical stimulation of the vagus nerve was studied in seven acute experiments on pigs. Feedback regulation of the HR over periods of 5 min was carried out. Three main populations of myelinated fibres were found. The performance of the controller was significantly better at amplitudes higher than those needed for stimulation of the myelinated components only. A 18% change in the duration of the RR interval could be controlled in all experiments. The possibility of closed-loop control of the HR seems to be promising.Financial support: European Commission for the NeuralPRO (FP5-Program, Research and Training Network)     

Effect of carotid sinus nerve stimulation pattern on cardiorespiratory responses.

The reflex responses to steady and intermittent stimulation of the carotid sinus nerve (CSN) were compared in anesthetized dogs. Intermittent stimulation was less effective than steady stimulation in reducing the arterial blood pressure, and the disparity was exaggerated after acute sinoaortic denervation. With the sinoaortic nerves intact, at low mean stimulation frequencies the heart rate responses were greater during intermittent than during steady CSN stimulation. At higher mean stimulation frequencies, however, steady CSN stimuli were more effective than were the intermittent type. After sinoaortic denervation, steady stimuli evoked greater heart rate responses than did intermittent stimuli over the entire mean frequency range studied. Reflex changes in respiratory depth and frequency were also greater during steady than during intermittent CSN stimulation. The greater efficacy of steady than of intermittent stimulation in evoking.the observed reflex cardiovascular and respiratory changes is probably ascribable to the pronounced frequency limitation at the first synapse of the baroreceptor reflex in the brain.     

Factorial analysis of the cardiovascular responses to carotid sinus nerve stimulation

The changes in arterial blood pressure, heart period, and respiration evoked by carotid sinus nerve (CSN) stimulation were studied in closed-chest, anesthetized dogs. Multifactorial regression equations were derived to express the various steady-state responses as functions of the parameters of stimulation. With the CSN and vagi intact, the changes in arterial pressure produced by CSN stimulation were much less pronounced than after the CSN and vagi were interrupted. When the CSN and vagi were intact, changes in stimulus duration had relatively little influence on heart period at the lower voltage levels. However, at higher voltages, increases in pulse duration produced substantial increments in heart period. TheRR interval increased progressively as the frequency of CSN stimulation was varied from 15 to 45 Hz; the magnitude of this effect varied directly with the stimulus voltage. This work was supported by U.S. Public Health Service Grants HL 15758 and HL 10951 from the National Heart and Lung Institute.     

Respiratory sinus arrhythmia and carotid baroreflex control of heart rate in endurance athletes and untrained controls

The purpose of this study was to compare the magnitude of the respiratory sinus arrhythmia, an index of cardiac vagal tone, and carotid baroreflex control of heart rate in endurance-trained athletes (n = 12, aged 20 +/- 1 years, means +/- SE) and untrained control subjects (n = 12, aged 22 +/- 1 year). Average R-R interval (ECG) and its variability were determined at rest under controlled breathing conditions, and the changes in R-R interval in response to brief applications of suction (-10, -25, -40 mmHg) and pressure (10 and 30 mmHg) to the carotid sinus region of the neck were also measured. The average R-R interval at rest was greater in the athletes vs. controls (1150 +/- 45 vs. 854 +/- 44 ms, P less than 0.001), but the standard deviation of the R-R intervals was similar in the two groups (72 +/- 15 vs. 70 +/- 9 ms). The magnitude of the tachycardia in response to neck pressure was also similar in the athletes and controls. Although the heart rate responses to neck suction were not significantly different between the two groups, there was a strong trend for attenuated bradycardic responses in the athletes at the two highest stimulus levels (70 +/- 14 vs. 97 +/- 25 ms and 86 +/- 14 vs. 145 +/- 38 ms for the -25 and -40 mmHg levels, respectively, P greater than 0.1). The results of this study do not support the postulate that cardiac vagal tone is enhanced in the endurance-trained state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Closed-loop nonlinear system identification via the vector optimal parameter search algorithm: application to heart rate baroreflex control

The vector optimal parameter search (VOPS) and the constrained optimal parameter search (COPS) are recently developed algorithms for closed-loop linear system identification. We extend both algorithms to be applicable to a closed-loop nonlinear system, which is characterized by a vector nonlinear autoregressive model. Monte Carlo simulations of nonlinear closed-loop systems were performed to compare the performance of the VOPS to the widely utilized vector least squares (VLS), the COPS and the total least squares (TLS) approaches. The relative error and linear transfer functions are computed to determine the accuracy of each method. The comparative results show that both the VOPS and COPS algorithms provide far superior parameter estimates than does the VLS for all simulation examples considered. The TLS provides better estimates than the VOPS, COPS and VLS when there is only observation noise present in the data. However, the performance of the TLS degrades considerably when the data are corrupted by dynamic noise. The clinical applicability of the two extended methods is examined by applying them to a classical physiological closed-loop system, the heart rate baroreflex. It was found that while both control and blockade of parasympathetic system conditions are dominated by linear dynamics, more nonlinearity was observed in the latter. This observation is statistically supported by the calculation of the mutual information of the data and their surrogates.     

Dynamic characteristics of carotid sinus pressure-nerve activity transduction in rabbits

The dynamic characteristics of the baroreflex neural arc from pressure input to efferent sympathetic nerve activity (SNA) reveal derivative characteristics in the frequency range of 0.01 to 0.8 Hz (i.e., the baroreflex gain augments with increasing frequency) and high-cut characteristics in the frequency range above 0.8 Hz (i.e., the baroreflex gain decreases with increasing frequency) in rabbits. The derivative characteristics accelerate the arterial pressure regulation via the baroreflex. The high-cut characteristics preserve the baroreflex gain against pulsatile pressure by attenuating the high-frequency components less necessary for arterial pressure regulation. However, to what extent the carotid sinus baroreceptor transduction from pressure input to afferent baroreceptor nerve activity (BNA) contributes to these characteristics remains unanswered. To test the hypothesis that the carotid sinus pressure-BNA transduction partly explains the derivative characteristics but not the highcut characteristics, we examined the dynamic BNA response to pressure input in the frequency range from 0.01 to 3 Hz by using a white noise analysis in 7 anesthetized rabbits. The transfer function from pressure input to BNA showed slight derivative characteristics in the frequency range from 0.01 to 0.3 Hz with approximately a 1.7-fold increase in dynamic gain, but it showed no high-cut characteristics. In conclusion, the carotid sinus baroreceptor transduction partly explained the derivative characteristics but not the high-cut characteristics of the baroreflex neural arc. The present results suggest the importance of the central processing from BNA to efferent SNA to account for the overall dynamic characteristics of the baroreflex neural arc.     

Effect of cervical sympathetic nerve stimulation on canine carotid sinus reflex.

In the chloralose-anesthetized dog the carotid sinus on one side of the neck was isolated vascularly. Pressure in the isolated sinus [carotid sinus pressure (CSP)], electrocardiogram, and systemic arterial pressure were recorded. Both vagosympathetic trunks were cut and the contralateral common carotid artery was occluded or the contralateral sinus nerve was cut to reduce reflex buffering of arterial pressure changes. By varying CSP from 50 to 250 mmHg the full range of the reflex response was examined. Electrical stimulation of the peripheral end of the cut ipsilateral cervical sympathetic nerve brought about a rapid decrease in mean arterial pressure (MAP) and heart rate (HR) at lower CSPs, no change in these variables at midrange CSPs, and a gradual increase at higher CSPs, such that the gain of the reflex was reduced (1.89 +/- 0.19 to 1.33 +/- 0.15 mmHg/mmHg). The decrease in MAP and HR at lower CSPs implies an increase in baroreceptor activity whereas the converse would appear to occur at higher CSPs. These responses attained a maximum value at low stimulus frequencies (less than 10 Hz).