Spontaneous Arterial Pressure Research Articles

Long‐term mechanical ventilation of an 8‐week‐old dog with idiopathic polyradiculoneuritis

AbstractA 2‐month‐old labrador retriever diagnosed with progressive polyradiculoneuritis was anaesthetised and mechanically ventilated with the aid of pressure control ventilation due to severe hypoventilation and hypoxaemia. Anaesthesia was maintained with propofol and midazolam constant‐rate infusions (CRIs). Over time, once the patient was showing spontaneous breathing attempts and arterial partial pressure of carbon dioxide was within normal range, ventilatory mode was switched to pressure support ventilation. The anaesthetic protocol was modified to maintain an appropriate level of anaesthesia with a minimum amount of fluid administered. The midazolam CRI was substituted by a sufentanil CRI, followed by a change to a dexmedetomidine CRI. An intensive nursing care protocol was established. Intermittent hyperthermia and peripheral oedema were the main complications observed. Ventilatory support was reduced until the patient was successfully weaned from the ventilator at the third attempt, after 116 hours of ventilatory support.

CRF1 and CRF2 receptors in the lateral hypothalamus differently modulate the baroreflex function in unanesthetized rats

The lateral hypothalamus (LH) is a diencephalic structure that has been considered part of the central circuitry regulating the baroreflex function. However, the local neurochemical mechanisms involved in baroreflex control by this hypothalamic area are poorly understood. Therefore, in the present study we investigated the role of corticotropin-releasing factor (CRF) neurotransmission within the LH acting via local CRF1 and CRF2 receptors in cardiac baroreflex responses in unanesthetized rats. For this, the baroreflex activity was assessed using two approaches: i) the pharmacological approach via intravenous infusion of vasoactive agents, and ii) the sequence analysis technique that evaluates reflex responses during spontaneous arterial pressure variations. The sequence analysis technique indicated that LH treatment with the selective CRF1 receptor antagonist CP376395 decreased the baroreflex effectiveness index, whereas the selective CRF2 receptor antagonist antisauvagine-30 increased the reflex shortening of pulse interval during spontaneous arterial pressure decreases. However, the pharmacological approach did not indicate effect of the bilateral microinjection of either CP376395 or antisauvagine-30 into the LH in the tachycardia evoked by blood pressure decrease or the reflex bradycardia caused by blood pressure increase. Overall, these findings indicate that CRF neurotransmission within the LH controls baroreflex function during a narrow range of physiological arterial pressure variations. Besides, results provide evidence that CRF1 and CRF2 receptors in the LH oppositely modulate the spontaneous baroreflex activity through different mechanisms.

Comparison of Causal and Non-causal Strategies for the Assessment of Baroreflex Sensitivity in Predicting Acute Kidney Dysfunction After Coronary Artery Bypass Grafting.

Coronary artery bypass graft (CABG) surgery may lead to postoperative complications such as the acute kidney dysfunction (AKD), identified as any post-intervention increase of serum creatinine level. Cardiovascular control reflexes like the baroreflex can play a role in the AKD development. The aim of this study is to test whether baroreflex sensitivity (BRS) estimates derived from non-causal and causal approaches applied to spontaneous systolic arterial pressure (SAP) and heart period (HP) fluctuations can help in identifying subjects at risk of developing AKD after CABG and which BRS estimates provide the best performance. Electrocardiogram and invasive arterial pressure were acquired from 129 subjects (67 ± 10 years, 112 males) before (PRE) and after (POST) general anesthesia induction with propofol and remifentanil. Subjects were divided into AKDs (n = 29) or no AKDs (noAKDs, n = 100) according to the AKD development after CABG. The non-causal approach assesses the transfer function from the HP-SAP cross-spectrum in the low frequency (LF, 0.04–0.15 Hz) band. BRS was estimated according to three strategies: (i) sampling of the transfer function gain at the maximum of the HP-SAP squared coherence in the LF band; (ii) averaging of the transfer function gain in the LF band; (iii) sampling of the transfer function gain at the weighted central frequency of the spectral components of the SAP series dropping in the LF band. The causal approach separated the two arms of cardiovascular control (i.e., from SAP to HP and vice versa) and accounted for the confounding influences of respiration via system identification and modeling techniques. The causal approach provided a direct estimate of the gain from SAP to HP by observing the HP response to a simulated SAP rise from the identified model structure. Results show that BRS was significantly lower in AKDs than noAKDs during POST regardless of the strategy adopted for its computation. Moreover, all the BRS estimates during POST remained associated with AKD even after correction for demographic and clinical factors. Non-causal and causal BRS estimates exhibited similar performances. Baroreflex impairment is associated with post-CABG AKD and both non-causal and causal methods can be exploited to improve risk stratification of AKD after CABG.

Baroreflex control of renal sympathetic nerve activity in early heart failure assessed by the sequence method.

The integrity of the baroreflex control of sympathetic activity in heart failure (HF) remains under debate. We proposed the use of the sequence method to assess the baroreflex control of renal sympathetic nerve activity (RSNA). The sequence method assesses the spontaneous arterial pressure (AP) fluctuations and their related changes in heart rate (or other efferent responses), providing the sensitivity and the effectiveness of the baroreflex. Effectiveness refers to the fraction of spontaneous AP changes that elicits baroreflex-mediated variations in the efferent response. Using three different approaches, we showed that the baroreflex sensitivity between AP and RSNA is not altered in early HF rats. However, the sequence method provided evidence that the effectiveness of baroreflex in changing RSNA in response to AP changes is markedly decreased in HF. The results help us better understand the baroreflex control of the sympathetic nerve activity. In heart failure (HF), the reflex control of the heart rate is known to be markedly impaired; however, the baroreceptor control of the sympathetic drive remains under debate. Applying the sequence method to a series of arterial pressure (AP) and renal sympathetic nerve activity (RSNA), we demonstrated a clear dysfunction in the baroreflex control of sympathetic activity in rats with early HF. We analysed the baroreflex control of the sympathetic drive using three different approaches: AP vs. RSNA curve, cross-spectral analysis and sequence method between AP and RSNA. The sequence method also provides the baroreflex effectiveness index (BEI), which represents the percentage of AP ramps that actually produce a reflex response. The methods were applied to control rats and rats with HF induced by myocardial infarction. None of the methods employed to assess the sympathetic baroreflex gain were able to detect any differences between the control and the HF group. However, rats with HF exhibited a lower BEI compared to the controls. Moreover, an optimum delay of 1 beat was observed, i.e. 1 beat is required for the RSNA to respond after AP changing, which corroborates with the findings related to the timing between these two variables. For delay 1, the BEI of the controls was 0.45±0.03, whereas the BEI of rats with HF was 0.29±0.09 (P<0.05). These data demonstrate that while the gain of the baroreflex is not affected in early HF, its effectiveness is markedly decreased. The analysis of the spontaneous changes in AP and RSNA using the sequence method provides novel insights into arterial baroreceptor reflex function.

Can a central blood volume deficit be detected by systolic pressure variation during spontaneous breathing?

BackgroundWhether during spontaneous breathing arterial pressure variations (APV) can detect a volume deficit is not established. We hypothesized that amplification of intra-thoracic pressure oscillations by breathing through resistors would enhance APV to allow identification of a reduced cardiac output (CO). This study tested that hypothesis in healthy volunteers exposed to central hypovolemia by head-up tilt.MethodsThirteen healthy volunteers were exposed to central hypovolemia by 45° head-up tilt while breathing through a facemask with 7.5 cmH2O inspiratory and/or expiratory resistors. A brachial arterial catheter was used to measure blood pressure and thus systolic pressure variation (SPV), pulse pressure variation and stroke volume variation . Pulse contour analysis determined stroke volume (SV) and CO and we evaluated whether APV could detect a 10 % decrease in CO.ResultsDuring head-up tilt SV decreased form 91 (±46) to 55 (±24) mL (mean ± SD) and CO from 5.8 (±2.9) to 4.0 (±1.8) L/min (p < 0.05), while heart rate increased (65 (±11) to 75 (±13) bpm; P < 0.05). Systolic pressure decreased from 127 (±14) to 121 (±13) mmHg during head-up tilt, while SPV tended to increase (from 21 (±15)% to 30 (±13)%). Yet during head-up tilt, a SPV ≥ 37 % predicted a decrease in CO ≥ 10 % with a sensitivity and specificity of 78 % and 100 %, respectively.ConclusionIn spontaneously breathing healthy volunteers combined inspiratory and expiratory resistors enhance SPV during head-up tilted induced central hypovolemia and allow identifying a 10 % reduction in CO. Applying inspiratory and expiratory resistors might detect a fluid deficit in spontaneously breathing patients.Trial registrationClinicalTrials.gov number NCT02549482 Registered September 10th 2015.

A Prospective Randomised Study of Postoperative Prophylactic Application of Sildenafil After Pediatric Cardiac Surgery

Postoperative aggravation of pulmonary hypertension after pediatric cardiac surgery due to temporary endothelial dysfunction may lead to sudden pulmonary arterial pressure rise with compromise of right ventricular function. Though treatment with inhaled nitric oxid (NO) has been successful, rebound pulmonary hypertension has been observed after NO withdrawal due to supression of endogenous NO sythase. Sildenafil has been shown to prevent this reaction and is widely used after pediatric cardiac surgery. The aim of our study was to evaluate the effectively of postoperative administration of oral sildenafil (1 mg/kg/day) in preventing postoperative pulmonary hypertensive crises. 21 patients after repair of complete atrioventricular canal (n=10) or ventricular septal defect (n=11) were randomly assigned to the study group or control group. The study group received sildenafil after surgery via nasogastric tube every eight hours for 48 hours, the control group received placebo. The primary outcome parameter was the number of pulmonary hypertensive events (spontaneous pulmonary arterial pressure rise to or above systemic arterial pressure). Secondary outcome parameters were: need for inotropic drugs, fluid balance, urinary output, days on the ventilator or in the intensive care unit (ICU). There was no difference in the number of pulmonary hypertensive events between both groups: median (IQR); 2 (0-6,5) sildenafil, 1 (0-2) placebo, p=0,67. Neither inotrope score, time on the ventilator, ICU length of stay, nor fluid balance differed significantly. Urinary output was significantly lower in the sildenafil group.

Cardiac output is not a significant source of low frequency mean arterial pressure variability

Spontaneous mean arterial pressure (MAP) variability may be mainly due to fluctuations in cardiac output (CO) and total peripheral resistance (TPR). While high frequency (HF ∼ 0.25 Hz) oscillations in MAP are ultimately driven by respiration, the source of low frequency (LF ∼ 0.1 Hz) fluctuations has not been fully elucidated. It is known that CO buffers these oscillations, but there is no evidence on its potential role in also generating them. The main goal was to determine whether CO is a source of LF variability in MAP. Six dogs were chronically instrumented to obtain beat-to-beat measurements of CO and MAP while the dogs were fully awake and at rest. A causal dynamic model was identified to relate the fluctuations in CO to MAP. The model was then used to predict the MAP fluctuations from the CO fluctuations. The CO fluctuations were able to predict about 70% of the MAP oscillations in the HF band but showed no predictive value in the LF band. Hence, respiration induces CO fluctuations in the HF band that, in turn, cause MAP oscillations, while TPR fluctuations appear to be the dominant mediator of LF fluctuations of MAP. CO is not a significant source of these oscillations, and it may only be responsible for dampening them, likely through the baroreflex.

ONE-SHOCK VERSUS CONTINUOUS DEFIBRILLATION IN AN 8-MIN VENTRICULAR FIBRILLATION CANINE MODEL OF CARDIAC ARREST

ObjectivesTo investigate the resuscitation effect of a one-shock defibrillation protocol versus conventional continuous defibrillation with treatment variation imposed by active compression-decompression CPR (ACD CPR) or standard CPR (STD CPR).Methods and...

Initial defibrillation versus initial chest compression in a 4-minute ventricular fibrillation canine model of cardiac arrest*

Previous laboratory and clinical studies have demonstrated that chest compression preceding defibrillation in prolonged ventricular fibrillation (VF) increases the likelihood of successful cardiac resuscitation. The lower limit of VF duration when preshock chest compression provides no benefit has not been specifically studied. We aimed to study the effect of order of defibrillation and chest compression on defibrillation and cardiac resuscitation in a 4-minute VF canine model of cardiac arrest. Prospective, randomized animal study. Key Laboratory of Cardiovascular Remodeling and Function Research and Department of Cardiology, QiLu Hospital. Twenty-four domestic dogs. VF was induced in anesthetized and ventilated canines. After 4 minutes of untreated VF, animals were randomly assigned to receive shock first or chest compression first. Animals in the shock-first group received an immediate single countershock of 360 J for <10 seconds, then 200 immediate compressions before pulse check or rhythm reanalysis. The ratio of compression to ventilation was 30:2. Interruptions to deliver rescue breaths were eliminated in this study. Animals in the chest compression-first group received 200 chest compressions before a single countershock; the other interventions were the same as for the shock-first group. End points were restoration of spontaneous circulation (ROSC), defined as spontaneous systolic arterial pressure >50 mm Hg, when epinephrine (0.02 mg/kg intravenously) was given, and resuscitation, defined as maintaining systolic arterial pressure >50 mm Hg at the 24-hour study end point. In the shock-first group, all animals achieved ROSC, and ten of 12 survived at the 24-hour study end point. In the chest compression-first group, 11 of 12 animals achieved ROSC, and nine of 12 survived at the 24-hour study end point. In this 4-minute VF canine model of cardiac arrest, the order of initial defibrillation or initial chest compression does not affect cardiac resuscitation.

Investigating feedforward neural regulation of circulation from analysis of spontaneous arterial pressure and heart rate fluctuations in conscious rats

It has been suggested in anesthetized animals that the occurrence of sequences of consecutive beats characterized by systolic arterial pressure (SAP) and RR or pulse interval (PI) changing in the opposite direction (SAP(+)/RR(-) and SAP(-)/RR(+), nonbaroreflex sequences) might represent the expression of neural cardiovascular regulatory mechanisms operating with feedforward characteristics. The aim of the present study was to study nonbaroreflex sequences in a more physiological experimental model, i.e., in conscious freely moving rats. We studied conscious rats before and after 1) complete autonomic blockade (n = 12), 2) sympathetic blockade (n = 10), 3) alpha (n = 7)- and beta (n = 8)-adrenergic blockade, and 4) parasympathetic blockade (n = 10). Nonbaroreflex sequences were defined as three or more beats in which SAP and PI of the following beat changed in the opposite direction. Complete autonomic blockade reduced the number of nonbaroreflex sequences (95.6 +/- 9.0 vs. 45.2 +/- 4.1, P < 0.001), as did sympathetic blockade (80.9 +/- 12.6 vs. 30.9 +/- 6.1, P < 0.001). The selective alpha-receptor blockade did not induce significant changes (80.9 +/- 12.5 in baseline vs. 79.0 +/- 14.7 after prazosin), whereas beta-receptor blockade significantly reduced nonbaroreflex sequence occurrence (80.9 +/- 12.5 in baseline vs. 48.9 +/- 15.3 after propranolol). Parasympathetic blockade produced a significant increase of nonbaroreflex sequences (95.1 +/- 6.9 vs. 136.0 +/- 12.4, P < 0.01). These results demonstrate the physiological role of the nonbaroreflex sequences as an expression of a feedforward type of short-term cardiovascular regulation able to interact dynamically with the feedback mechanisms of baroreflex origin in the neural control of the sinus node.

Online correlation of spontaneous arterial and intracranial pressure fluctuations in patients with diffuse severe head injury

Determination of relevant clinical monitoring parameters for helping guide the intensive care therapy in patients with severe head injury, is one of the most demanding issues in neurotrauma research. New insights into cerebral autoregulation and metabolism have revealed that a rigid cerebral perfusion pressure (CPP) regimen might not be suitable for all severe head injured patients. We thus developed an online analysis technique to monitor the correlation (AIρ) between the spontaneous fluctuations of the mean arterial blood pressure (MABP) and the intracranial pressure (ICP). In addition, brain tissue oxygen (PtiO2) and metabolic microdialysate measures including glucose and lactate were registered. We found that in patients with good outcome, the AIρ values were significantly lower as compared with patients with poor outcome. Accordingly, microdialysate glucose and lactate were significantly higher in the good outcome group. We conclude that online determination of AIρ offers a valuable additional and technically easily performable tool for guidance of therapy in patients with severe head injury.

Baroreceptor Reflex Sensitivity Estimated by the Sequence Technique is Reliable in Rats

The following is the abstract of the article discussed in the subsequent letter: 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 heart beats (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.

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.

Muscle sympathetic baroreflex sensitivity is different at rest and during evoked hypotension.

Arterial muscle sympathetic baroreflexes are frequently assessed using pharmacologically evoked decrements in arterial blood pressure. Since drugs administered for baroreflex tests may themselves alter the sympathetic response to evoked pressure variations we proposed a method to determine sympathetic baroreflex gain during spontaneous fluctuations in arterial pressure at rest and tested the null hypothesis that baroreflex gain assessed during spontaneous fluctuations in arterial pressure equals baroreflex gain determined during evoked hypotension. Muscle sympathetic nerve activity (MSA), arterial blood pressure, and heart rate were assessed at rest in 15 healthy volunteers (age: 29 years +/- 5, mean +/- SD). All diastolic pressures sampled during a 5 min period were grouped in intervals of 1 mmHg and the burst incidence per interval was calculated. The slope of the regression line of burst incidence and diastolic pressure represents baroreflex gain during spontaneous fluctuations in arterial pressure. In the same volunteers, burst incidence was also determined over 30 s periods before and after a decrease in arterial pressure evoked by nitroprusside (SNP, 2-3 micro g kg(-1) i. v.). The relationship between mean MSA burst incidence and diastolic arterial pressure was compared before and after the pressure decrease yielding an average baroreflex "gain" during evoked hypotension. Average baroreflex "gain" assessed by this conventional method was compared to baroreflex gain assessed during spontaneous arterial pressure fluctuations by Bland-Altman analysis and correlation analysis. Resting MSA was 28 bursts/100 heart beats +/- 10 at a diastolic pressure of 71 mmHg +/- 11. Baroreflex gain during spontaneous arterial pressure fluctuations was 4.0% mmHg(-1) +/- 1.9 and was significantly greater than the average "gain" assessed during evoked hypotension (2.1% mmHg(-1) +/- 1.6). Individual values for baroreflex gain determined with both methods did not correlate (r = 0.1, p = 0.8). Baroreflex gain as determined during spontaneous arterial pressure fluctuations differs from that assessed during SNP-evoked hypotension, possibly due to intrinsic effects of SNP on the baroreflex. Thus, caution should be exercised when interpreting baroreflex gain derived during SNP-evoked hypotension.

Time-varying properties of renal autoregulatory mechanisms

In order to assess the possible time-varying properties of renal autoregulation, time-frequency and time-scaling methods were applied to renal blood flow under broad-band forced arterial blood pressure fluctuations and single-nephron renal blood flow with spontaneous oscillations obtained from normotensive (Sprague-Dawley, Wistar, and Long-Evans) rats, and spontaneously hypertensive rats. Time-frequency analyses of normotensive and hypertensive blood flow data obtained from either the whole kidney or the single-nephron show that indeed both the myogenic and tubuloglomerular feedback (TGF) mechanisms have time-varying characteristics. Furthermore, we utilized the Renyi entropy to measure the complexity of blood-flow dynamics in the time-frequency plane in an effort to discern differences between normotensive and hypertensive recordings. We found a clear difference in Renyi entropy between normotensive and hypertensive blood flow recordings at the whole kidney level for both forced (p < 0.037) and spontaneous arterial pressure fluctuations (p < 0.033), and at the single-nephron level (p < 0.008). Especially at the single-nephron level, the mean Renyi entropy is significantly larger for hypertensive than normotensive rats, suggesting more complex dynamics in the hypertensive condition. To further evaluate whether or not the separation of dynamics between normotensive and hypertensive rats is found in the prescribed frequency ranges of the myogenic and TGF mechanisms, we employed multiresolution wavelet transform. Our analysis revealed that exclusively over scale ranges corresponding to the frequency intervals of the myogenic and TGF mechanisms, the widths of the blood flow wavelet coefficients fall into disjoint sets for normotensive and hypertensive rats. The separation of the scales at the myogenic and TGF frequency ranges is distinct and obtained with 100% accuracy. However, this observation remains valid only for the whole kidney blood pressure/flow data. The results suggest that understanding of the time-varying properties of the two mechanisms is required for a complete description of renal autoregulation.

Spontaneous renal blood flow autoregulation curves in conscious sinoaortic baroreceptor-denervated rats.

These experiments examined whether the conscious sinoaortic baroreceptor-denervated (SAD) rat, owing to its high spontaneous arterial pressure (AP) variability, might represent a model for renal blood flow (RBF) autoregulation studies. In eight SAD and six baroreceptor-intact rats, AP and RBF were recorded (1-h periods) before and after furosemide (10 mg/kg followed by 10 mg. kg(-1). h(-1) iv) administration. In control conditions, AP variability was markedly enhanced in SAD rats (coefficient of variation: 16.0 +/- 1.2 vs. 5.4 +/- 0.5% in intact rats), whereas RBF variability was only slightly increased (8.7 +/- 0.6 vs. 6.1 +/- 0.5% in intact rats), suggesting buffering by autoregulatory mechanisms. In SAD rats, but not in intact rats, the AP-RBF relationships could be modeled with a four-parameter sigmoid Weibull equation (r(2) = 0.24 +/- 0.07, 3,600 data pairs/rat), allowing for estimation of an autoregulatory plateau (10.1 +/- 0.7 ml/min) and a lower limit of RBF autoregulation (P(LL) = 93 +/- 6 mmHg, defined as AP at RBF 5% below the plateau). After furosemide treatment, autoregulation curves (r(2) = 0.49 +/- 0.07) in SAD rats were shifted downward (plateau = 8.6 +/- 0.8 ml/min) and rightward (P(LL) = 102 +/- 5 mmHg). In five of six intact rats, P(LL) became measurable (104 +/- 1 mmHg), albeit with limited accuracy (r(2) = 0.09 +/- 0.03). In conclusion, the conscious SAD rat offers the possibility of describing RBF autoregulation curves under dynamic, unforced conditions. The tubuloglomerular feedback and myogenic mechanisms cooperate in setting P(LL) and thus in stabilizing RBF during spontaneous depressor episodes.

Spontaneous baroreflex modulation of heart rate and heart rate variability during orthostatic stress in tetraplegics and healthy subjects.

This study was addressed to investigate the contribution of vagal and sympathetic mechanisms to the genesis of low-frequency (LF) oscillations of RR-interval. To this aim, we utilized the pathophysiological model of tetraplegics, who have intact vagal afferent and efferent pathways of the baroreceptor reflex arc but interrupted medullary-spinal sympathetic pathways. We studied nine complete, traumatic, tetraplegics (C4-C7, TET) and 10 normally healthy subjects (NR) at rest and during physiological baroreceptors unloading induced by 70 degrees head-up tilt. Autoregressive power spectral analysis was used to investigate RR-interval and systolic arterial pressure (SAP) variabilities. Baroreflex modulation of sinus node was assessed by the spontaneous baroreflex sequences method. Both at-rest and during-tilt LF and high frequency (HF) components were detected in RR-interval of NR, whereas in TET only the HF component was observed in both conditions (with one exception). Baroreflex sensitivity (BRS) did not significantly differ between TET and NR at rest, and underwent a significant and similar decrease during tilt in both groups, being accompanied in NR by a significant increase in LF relative power. Spectral analysis of SAP provided results similar to RR-interval. Tilt also slowed the centre frequency of the LF components of RR-interval and SAP. During unperturbed physiological conditions, a change in efferent vagal activity to the heart from baroreflex stimulation by spontaneous arterial pressure changes, is unlikely to contribute on its own to the genesis of LF heart period oscillations in humans who lack the ability to modulate sympathetic nerve traffic to the heart. However, the possibility that a baroreflex modulation of LF oscillations require an intact sympathetic control should be carefully considered.

Effect of desipramine on spontaneous arterial pressure oscillations in the rat

There has been no previous report on the effect of the noradrenaline uptake inhibitor desipramine on short-term variability of arterial pressure. Mean arterial pressure was recorded in 9 conscious resting rats during 4 consecutive 30-min periods: (1) under baseline conditions, (2) after desipramine administration (2 mg/kg i.v., followed by 1 mg/kg every hour), then after (3) cardiac autonomic blockade with methylatropine and atenolol, and (4) α-adrenoceptor blockade with phentolamine. Fast Fourier transform analysis was applied to beat-to-beat data after resampling at 10 Hz of consecutive 205-s time series. Desipramine did not change the mean level and overall variability of mean arterial pressure. However, spectral power in the mid-frequency (0.3–0.5 Hz) band containing the Mayer waves was reduced by more than 80%, and power in the low-frequency (0.05–0.2 Hz) band was enhanced by approximately 50%, especially due to the appearance of a major oscillation centred at 0.095±0.005 Hz. This slow oscillation was further enhanced after cardiac autonomic blockade and was abolished after α-adrenoceptor blockade. In conclusion, desipramine profoundly alters short-term arterial pressure variability in resting rats, mainly by shifting vasomotor waves from 0.4 to 0.1 Hz. Desipramine may prove a valuable pharmacological tool to study the dynamic aspects of arterial pressure control.

Investigating feed-forward neural regulation of circulation from analysis of spontaneous arterial pressure and heart rate fluctuations.

Analysis of spontaneous fluctuations in systolic arterial pressure (SAP) and pulse interval (PI) reveals the occurrence of sequences of consecutive beats characterized by SAP and PI changing in the same (+PI/+SAP and -PI/-SAP) or opposite (-PI/+SAP and +PI/-SAP) direction. Although the former reflects baroreflex regulatory mechanisms, the physiological meaning of -PI/+SAP and +PI/-SAP is unclear. We tested the hypothesis that -PI/+SAP and +PI/-SAP "nonbaroreflex" sequences represent a phenomenon modulated by the autonomic nervous system reflecting a feed-forward mechanism of cardiovascular regulation. We studied anesthetized rabbits before and after (1) complete autonomic blockade (guanethidine+propranolol+atropine, n=13; CAB), (2) sympathetic blockade (guanethidine+propranolol, n=15; SB), (3) parasympathetic blockade (atropine, n=16), (4) sinoaortic denervation (n=10; SAD), and (5) controlled respiration (n=10; CR). Nonbaroreflex sequences were defined as >/=3 beats in which SAP and PI of the following beat changed in the opposite direction. CAB reduced the number of nonbaroreflex sequences (19. 1+/-12.3 versus 88.7+/-36.6, P<0.05), as did SB (25.3+/-11.7 versus 84.6+/-23.9, P<0.001) and atropine (11.2+/-6.8 versus 94.1+/-32.4, P<0.05). SB concomitantly increased baroreflex sensitivity (1.18+/-0. 11 versus 0.47+/-0.09 ms/mm Hg, P<0.01). SAD and CR did not significantly affect their occurrence. These results suggest that nonbaroreflex sequences represent the expression of an integrated, neurally mediated, feed-forward type of short-term cardiovascular regulation able to interact dynamically with the feedback mechanisms of baroreflex origin in the control of heart period.

Synergism Between Sevoflurane and Intravenous Fentanyl on A delta and C Somatosympathetic Reflexes in Dogs

In this study, we defined the nature of the interactions between sevoflurane and fentanyl on spontaneous and reflex-evoked sympathetic activity, resting heart rate (HR), and mean arterial pressure (MAP). Spontaneous renal sympathetic nerve activity (RSNA) and A delta- and C-fiber-mediated somatosympathetic reflexes, evoked by electrical stimulation of radial nerves, and HR and MAP were recorded in anesthetized dogs. In one group, the effects of incremental doses of 2-64 micrograms/kg fentanyl i.v. were observed. It had a greater inhibitory effect on C than on A delta reflexes, which were abolished by mean cumulative doses of 64 micrograms/kg and approximately 128 micrograms/kg, respectively. Although 1.5% sevoflurane reduced C reflexes by 28% and A delta reflexes by only 12%, it reduced the total doses of fentanyl required for their abolition to 32 micrograms/kg and 64 micrograms/kg, respectively. Mean RSNA, HR, and MAP values were reduced by 46%, 54%, and 30%, respectively, by fentanyl alone and by 23%, 11%, and 17%, respectively, in response to 1.5% sevoflurane. The combination of fentanyl and sevoflurane caused reductions of 44%, 54%, and 41%, respectively, which indicates a less than additive effect. These results indicate that sevoflurane interacts synergistically with fentanyl to depress A delta and C somatosympathetic reflexes, whereas for RSNA, HR, and MAP, their effects were less than the additive. Although fentanyl caused a greater depression of C than of A delta reflexes to the point of abolition, the maximal depression of spontaneous sympathetic activity, heart rate, and arterial pressure occurred at smaller doses. The combined depressant effects of sevoflurane and fentanyl were synergistic on somatosympathetic reflexes but were less than additive on spontaneous sympathetic activity, heart rate, and arterial pressure.