Pharmacological Autonomic Blockade Research Articles

The role of the autonomic nervous system in the patterns of heart rate fragmentation

Although rapid oscillations in heart rate (HR) are commonly attributed to vagal modulation of the heart, an ultra-rapid pattern of HR variation has recently been studied and named heart rate fragmentation (HRF). ObjectiveConsidering that the underlying mechanisms of HRF are unknown, this study aims to evaluate the influence of the autonomic nervous system on HRF in rats. MethodsElectrocardiogram recordings were performed in awake rats at baseline conditions and after selective or combined pharmacological autonomic blockade. Series of RR intervals were calculated and HRF indices were computed, namely percentage of inflection points (PIP), percentage of patterns with zero (W0), one (W1), two (W2) or three (W3) inflection points, and percentage of patterns with only hard (WH), soft (WS) or mixed (WM) inflection points. Moreover, the correlations between HRF indices and several important heart rate variability (HRV) indices were estimated. ResultsPIP and W3 increased while W1 decreased after autonomic blockade (sympathetic, parasympathetic or combined). In contrast, the parasympathetic blockade noticeably decreased hard (WH) and increased soft (WS) HR transitions. Except for W0, HRF patterns grouped by the number of inflection points were not correlated to any studied HRV index. In contrast, patterns grouped by the type of inflection points are highly correlated to magnitude-dependent HRV indices. ConclusionCardiac sympathetic and parasympathetic influences similarly decrease HRF, while the parasympathetic control markedly increases the hard HR inflection points. Further studies should be conducted to verify whether the autonomic nervous system plays a different role in diseases marked by autonomic imbalance.

Baseline intrinsic heart rate and response to ivabradine treatment in patients with inappropriate sinus tachycardia.

BackgroundTreatment with ivabradine became a new therapeutic alternative for patients with inappropriate sinus tachycardia (IST). The aim was to determine a relation between intrinsic heart rate (IHR) and response to ivabradine treatment.MethodsTwenty‐seven patients (mean age 37 ± 11; 23 women) with symptomatic IST despite medical treatment were recruited into the study. Resting ECG, 24‐hr ECG monitoring (24hECG), exercise treadmill test, and symptoms evaluation were performed initially and after 60 days on ivabradine. IHR was acquired at baseline after pharmacological autonomic blockade.ResultsNineteen patients (70%) were classified as abnormal IHR group (AIHR) while eight showed normal IHR (NIHR). No significant differences in ECG parameters were found between NIHR and AIHR subgroups, while baseline exercise capacity was higher in AIHR patients (10.9 vs. 9.5 METs, p < .05). Ivabradine treatment resulted in significant reduction in resting heart rate, average 24hECG heart rate, improvement in exercise capacity and reduction of symptoms in both subgroups. Nevertheless, favorable influence of ivabradine was significantly more exaggerated in AIHR subgroup (HR 116 vs. 90 bpm, av. HR 98 vs. 79 bpm, 10.9 vs. 13.6 METS, EHRA score 3.1 vs. 1.1, p < .001 for all) than in NIHR patients (HR 112 vs. 98 bpm, av. HR 97 vs. 88 bpm, 9.5 vs. 11.1 METs, EHRA score 3.1 vs. 1.9; p < .05 for all).ConclusionsIntrinsic heart rate may be useful in predicting response to ivabradine in patients with IST. More intense response to ivabradine in patients with AIHR may be attributed to different pathophysiological mechanisms underlying IST in AIHR and NIHR groups.

Cardiovascular and ventilatory interactions in the facultative air-breathing teleost Pangasianodon hypophthalmus.

All vertebrates possess baroreceptors monitoring arterial blood pressure and eliciting reflexive changes in vascular resistance and heart rate in response to blood pressure perturbations imposed by, e.g., exercise, hypoxia, or hemorrhage. There is considerable variation in the magnitude of the baroreflex amongst vertebrate groups, making phylogenetic trends and association with major evolutionary events such as air-breathing and endothermy, difficult to identify. In the present study, we quantified the baroreflex in the facultative air-breathing catfish Pangasianodon hypophthalmus. Using a pharmacological approach, we quantified the cardiac limb of the baroreflex and by subjecting fish to hypoxia and by stimulation with NaCN with and without pharmacological autonomic blockade; we also examined the cardiovascular regulation associated with air-breathing. As in most other air-breathing fish, air-breathing elicited a substantial tachycardia. This tachycardia was abolished by cholinergic muscarinic pharmacological blockade, which also abolished the cardiac limb of the baroreflex, and consequently such fish failed to maintain their arterial blood pressure when air-breathing. In higher vertebrate classes, baroreceptors elicit ventilatory changes; however, whether this is the case in fish has not previously been investigated. Pangasianodon hypophthalmus demonstrated a prominent increase in ventilation during imposed hypotension. Collectively, these results demonstrate, for the first time, an efficient baroreflex in an air-breathing fish, point towards involvement of baroreceptors in blood pressure regulation during air-breathing, and show a correlation between blood pressure and ventilation, providing additional information on the origin of this link.

Cardiac and behavioral effects of social isolation and experimental manipulation of autonomic balance.

Improved understanding of how depression and social isolation interact to increase cardiac morbidity and mortality will improve public health. This experiment evaluated the effect of pharmacological autonomic blockade on cardiac and behavioral reactivity following social isolation in prairie voles. Experiment 1 validated the dose and time course of pharmacological autonomic antagonism of peripheral β-adrenergic (atenolol) and muscarinic cholinergic receptors (atropine methyl nitrate), and Experiment 2 used a novel protocol to investigate behavioral responses in the tail suspension test during pharmacological autonomic blockade as a function of social isolation (vs. paired control). Prairie voles isolated for 4 weeks (vs. paired) displayed significantly elevated heart rate and reduced heart rate variability. Autonomic receptor antagonism by atenolol led to exaggerated reductions in heart rate and standard deviation of normal-to-normal intervals, and lower amplitude of respiratory sinus arrhythmia in the isolated group (vs. paired). Administration of atropine led to an attenuated increase in heart rate in the isolated group (vs. paired), and similar near-zero levels of respiratory sinus arrhythmia amplitude in both groups. During the tail suspension test, isolated animals (vs. paired) displayed significantly greater immobility. In paired animals, atenolol administration did not influence immobility; atropine administration increased the duration of immobility (vs. vehicle). In isolated animals, atenolol administration increased the duration of immobility; atropine did not influence immobility duration (vs. vehicle). The current study contributes to our understanding of differential effects of social isolation and autonomic imbalance on cardiac and behavioral reactivity.

Chronic treatment with angiotensin-converting enzyme inhibitor increases cardiac fibrosis in young rats submitted to early ovarian failure.

We investigated whether the treatment with enalapril maleate, combined with aerobic physical training, promotes positive effects on the autonomic balance, the morphology and the cardiac function in female rats submitted to early ovarian failure. Thirty-five female Wistar rats, ovariectomized at 10weeks of age, were assigned into Ovariectomized rats (OVX) and Ovariectomized rats treated with enalapril maleate (OVX-EM, 10mg-1·kg-1·d-1) Each group was subdivided into sedentary and trained (aerobic swimming training for 10weeks). All animals were submitted to a) double pharmacological autonomic blockade, b) study of morphology and cardiac function by echocardiography, and c) analysis of cardiac fibrosis. The OVX-EM sedentary group showed a significant increase in cardiac fibrosis, relative heart weight, interventricular septum thickness and increased sympathetic participation and reduced participation of the vagal tone in the determination of the basal heart rate when compared to the OVX sedentary group. Physical training reduced cardiac fibrosis in both groups, however, with less intensity in the OVX-EM group. It also increased the absolute and relative heart weight and the end-systolic volume. Finally, the OVX-EM trained group showed higher values for left ventricular end-systolic volume and lower values for ejection fraction and shortening fraction than the sedentary OVX-EM group. Enalapril maleate exacerbated cardiac fibrosis and increased sympathetic participation in the basal heart rate determination, without significantly affecting the cardiac function. Aerobic physical training did not change the cardiac autonomic control, but reduced cardiac fibrosis and had little effect on the cardiac function.

A study of pharmacological vs. pathological autonomic nervous system blockade in humans, using heart rate chaotic dynamics.

Pathological blocking of the Autonomous Nervous System (ANS) is diagnosed for patients having Autonomic Neuropathy passing a well-defined set of criteria. In this work, It is shown that standard analysis can be complemented by a study of the chaotic dynamics of the Heart Rate (HR), over a period of 12 min in the resting position. It was found that patients who suffering from ANS blockade, typically exhibit a smaller degree of fractality and complexity of the chaotic attractor reconstructed from the time series of the HR signal. These dynamical measures are more evident in normal human subjects that have been subjected to pharmacological ANS blockade.

Progressive development of cardiomyopathy following altered autonomic activity in status epilepticus.

Seizures are associated with altered autonomic activity, which has been implicated in the development of cardiac dysfunction and structural damage. This study aimed to investigate the involvement of the autonomic nervous system in seizure-induced cardiomyopathy. Male Sprague-Dawley rats (320-350 g) were implanted with EEG/ECG electrodes to allow simultaneous telemetric recordings during seizures induced by intrahippocampal (2 nmol, 1 μl/min) kainic acid and monitored for 7 days. Seizure activity occurred in conjunction with increased heart rate (20%), blood pressure (25%), and QTc prolongation (15%). This increased sympathetic activity was confirmed by the presence of raised plasma noradrenaline levels at 3 h post-seizure induction. By 48 h post-seizure induction, sympathovagal balance was shifted in favor of sympathetic dominance, as indicated by both heart rate variability (LF/HF ratio of 3.5 ± 1.0) and pharmacological autonomic blockade. Functional cardiac deficits were evident at 7 and 28 days, as demonstrated by echocardiography showing a decreased ejection fraction (14% compared with control, P < 0.05) and dilated cardiomyopathy present at 28 days following seizure induction. Histological changes, including cardiomyocyte vacuolization, cardiac fibrosis, and inflammatory cell infiltration, were evident within 48 h of seizure induction and remained present for up to 28 days. These structural changes most probably contributed to an increased susceptibility to aconitine-induced arrhythmias. This study confirms that prolonged seizure activity results in acute and chronic alterations in cardiovascular control, leading to a deterioration in cardiac structure and function. This study further supports the need for modulation of sympathetic activity as a promising therapeutic approach in seizure-induced cardiomyopathy.

Cardiovascular function alterations induced by acute paradoxical sleep deprivation in rats

Sleep loss has been implicated in triggering the hypertension. The goal of the present study was investigated the possible mechanisms underlying cardiovascular alterations after acute paradoxical sleep deprivation (PSD). Male Wistar rats were assigned in two experimental groups: (1) control and (2) PSD for 24 h using the modified single platform method. Paradoxical sleep deprived rats exhibited higher blood pressure, heart rate (HR) and impaired baroreceptor sensitivity. After pharmacological autonomic double blockade (propranolol and methylatropine administration), intrinsic heart rate was decreased after PSD. The PSD rats showed a reduction in the vagal tone without affecting sympathetic tone. Isoproterenol administration (0.001, 0.01 and 1 µg/kg) induced an increase in ΔHR responses in PSD group. Electrocardiographic analysis in response to β-adrenergic stimulation indicated that PSD contributed to ventricular cardiac arrhythmias. Our findings suggest that acute paradoxical sleep loss induce cardiovascular alterations, autonomic imbalance accompanied by impaired baroreflex sensitivity and increased arrhythmia susceptibility.

Resting heart rate variability and heart rate recovery after submaximal exercise

Aerobic training accelerates Heart Rate Recovery after exercise in healthy subjects and in patients with coronary disease. As shown by pharmacological autonomic blockade, HRR early after exercise is dependent primarily on parasympathetic reactivation. Thus, accelerated HRR early after exercise in endurance-trained athletes may be attributed to augmented parasympathetic reactivation. In the present study, we tested the hypothesis that the HRR early after submaximal exercise is related to the pre-exercise parasympathetic modulation. Thirty endurance-trained athletes (20 males, 50 ± 7 years) and thirty control subjects (20 males, 52 ± 6 years) performed a submaximal exercise on a cyclo-ergometer. Pre-exercise resting short-term heart rate variability (HRV) parameters in time and frequency-domains were correlated with HRR during the first 30 s, 1 and 2 min after cessation of exercise. We found that HRR was statistically significantly faster in athletes than in controls at all examination time points (p < 0.05). HF, SDNN and RMSSD were statistically significantly higher in athletes than in controls (p < 0.05), but other resting HRV parameters were not statistically different between groups. After 30 s, 1 and 2 min of recovery, HRR correlation with total power, HF, HFnu and RMSSD was positive, while the correlation with LF/HF was negative for small and positive for larger values. The opposite was true for SDNN. These findings support the hypothesis that HRR early after submaximal exercise is related to resting parasympathetic modulation in the middle-aged subjects. In addition, they suggested an optimal range of HRV for maximal HRR after exercise.

Regulation of the Intracerebroventricular Administration of Brain-Derived Neurotrophic Factor on Baroreflex Function and Insulin Sensitivity in Rats

"In addition to its well-established neurotrophic effects, brain-derived neurotrophic factor (BDNF) has also been shown to regulate glucose metabolism. The present study was conducted to determine whether BDNF has effects on baroreflex sensitivity (BRS) and whole-body insulin sensitivity through modulation of autonomic nervous function in normal rats. Male Sprague-Dawley rats were treated with intracerebroventricular BDNF (20 μg per rat, 10μl; BDNF) or artificial cerebrospinal fluid (10 μl; control) at an infusion rate of 1 μl/min in conscious state. The whole-body insulin sensitivity was determined by the euglycemic hyperinsulinemic clamp technique. BRS in response to phenylephrine (PE-BRS) or sodium nitroprusside (NP-BRS) was assessed using linear regression analysis. The sympathetic and parasympathetic influences on BRS were investigated by pharmacological autonomic blockade. When compared to the control rats, blood glucose levels were slightly but significantly decreased in BDNF-treated rats. However, plasma insulin levels were reduced by about 30%. The whole-body insulin sensitivity was increased in BDNF-treated rats. In addition, blood pressure was increased but heart rate remained unchanged after BDNF treatment. Enhanced PE-BRS was also observed in the BDNF-treated rats, which was attributed to the abnormal parasympathetic activation as revealed by the results of the pharmacological blockade study with methylatropine. Results of the present demonstrate that central BDNF plays an important role in the regulation of whole-body insulin sensitivity and baroreflex function. The data indicate that the alteration of autonomic nervous function may play a role in the effects of BDNF."

Determinants of atrial fibrillation in an animal model of obesity and acute obstructive sleep apnea

Obesity and obstructive sleep apnea (OSA) are risk factors for atrial fibrillation (AF), but the underlying mechanisms are poorly understood. The purpose of this study was to assess the mechanisms underlying AF promotion by obesity and OSA in rat models. Zucker obese rats (ORs) and lean rats (LRs) were intubated and ventilated with air and 2% isoflurane. OSA was mimicked by stopping the ventilator and closing the airway for 40 seconds. For nonobstructive control periods, the protocol was repeated with an open airway. Fifteen seconds after apnea onset, AF susceptibility was tested with 6 atrial burst pacing cycles (25 Hz, 3 seconds, 1-second intercycle pauses). AF was not inducible in ORs or LRs at baseline or in nonobstructive control periods. AF was induced in 24 of 28 ORs (85.7%) vs 5 of 18 LRs (27.8%) during obstructive apnea (P <.001). Negative intrathoracic pressure generation (esophageal pressure monitoring) was substantial during obstructive apnea. Echocardiography showed left ventricular hypertrophy with diastolic dysfunction in ORs. Obstructive apnea caused acute left atrial (LA) dilation, increasing LA diameter significantly more in ORs than in LRs. To clarify AF mechanisms, 24 AF-inducible ORs were divided into 4 groups: saline (n = 5), pharmacologic autonomic blockade (n = 7), respiratory muscle paralysis with rocuronium (n = 6), and inferior vena cava (IVC) balloon occlusion to unload the LA (n = 6). Balloon catheter-induced IVC occlusion prevented LA distension during obstructive apnea, leading to 83.3% AF prevention (P <.05). Rocuronium also was protective (66.7%), but autonomic blockade had smaller effects (42.9% prevention). Obesity and acute obstructive apnea interacted to promote AF in this model. Forced inspiration-induced acute LA distension related to diastolic dysfunction may be an important component of the arrhythmogenic substrate for AF during OSA episodes in obese patients.

The Impact of Pharmacologic Sympathetic and Parasympathetic Blockade on Atrial Electrogram Characteristics in Patients with Atrial Fibrillation

Ablation of atrial autonomic inputs exerts antifibrillatory effects. However, because ablation destroys both myocardium and nerve cells, the effect of autonomic withdrawal alone remains unclear. We therefore examined the effects of pharmacologic autonomic blockade (PAB) on frequency and fractionation in patients with atrial fibrillation (AF). Esmolol and atropine were administered and electrograms were recorded simultaneously from both atria and the coronary sinus. In 17 patients, AF was recorded for 5 minutes and dominant frequency (DF) and continuous activity (CA) were compared before and during PAB. Examination of the pooled data (537 sites, 17 patients) revealed a statistically significant decrease in mean DF (5.61–5.43Hz, P < 0.001) during PAB. Site-by-site analysis showed that 67% of sites slowed (0.45 ± 0.59 Hz), whereas 32% accelerated (0.49 ± 0.59Hz). Fractionation was reduced: median CA decreased from 31% to 26% (P < 0.001). In patient-by-patient analysis, mean DF/median CA decreased in 13 of 17 patients and increased in four. The spatial heterogeneity of DF decreased in nine of 17 patients (spatial coefficient of variation of DF at "nondriver sites" decreased by a mean of 2%). PAB decreases DF and CA in the majority of sites. Given the complexity of interactions between atrial cells during AF, the effects of PAB on DF and fractionation are more heterogeneous than the effects of PAB on isolated cells.

Identification of low and high frequency ranges for heart rate variability and blood pressure variability analyses using pharmacological autonomic blockade with atropine and propranolol in swine.

Understanding autonomic nervous system functioning, which mediates behavioral and physiological responses to stress, offers great potential for assessing farm animal stress and welfare. Evaluation of heart rate variability (HRV) and blood pressure variability (BPV), using time and frequency domain analyses may provide a sensitive and reliable measure of affective states and stress-mediated changes in sympathetic and parasympathetic tones. The aim of this research was to define low (LF) and high frequency (HF) power spectral ranges using pharmacological autonomic blockade, and to examine HRV and BPV parameter changes in response to atropine and propranolol in swine. Ten, 13-week old, barrows (n=6) and gilts (n=4) underwent surgery to place an intra-cardiac electrode and a blood pressure catheter attached to a biotelemetric transmitter; pigs had a 3-week recovery period prior to data collection. Each pig was subjected to administration of 4 intravenous (i.v.) drug treatments: a control treatment, 3 mL of saline, and 3 blockade treatments; 0.1 mg/kg of atropine, 1.0 mg/kg of propranolol, and .1 mg/kg of atropine together with 1.0 mg/kg of propranolol. All treatments were delivered by injection in the jugular vein with a minimum of 48 h between individual treatments. Behavior, ECG and blood pressure data were recorded continuously for a total of 1h, from 30 min pre-injection to 30 min post-injection. For data analyses, two 512-beat intervals were selected for each treatment while the pig was lying and inactive. The first interval was selected from the pre-injection period (baseline), and the second was selected between 10 and 30 min post-injection. Time and frequency domain (power spectral density) analyses were performed on each data interval. Subsequent, LF and HF bands from the power spectral densities were defined based on general linear and regression analyses. The HRV and BPV were computed with a covariate (baseline) factorial analysis of treatment by sex interaction, and day of injection, with mixed models and Tukey's post-hoc tests. The best-fit range for LF was 0.0-0.09 Hz, and HF was 0.09-2.0 Hz (r²: 0.41 and 0.43, respectively). Propranolol and saline injections led to a greater overall total power and overall higher inter-beat interval, HF and LF power. Atropine led to a dominant sympathovagal balance of the cardiac activity in pigs. In addition, atropine led to an increase in LF power of both systolic and diastolic blood pressures in gilts suggesting vagal tone mediation of BPV. The understanding of autonomic regulation of HRV and BPV in domestic swine facilitates our ability to detect and quantify stress responses, and broadens its application in assessing farm animal welfare.

Electrophysiological features in patients with sinus node dysfunction and vasovagal syncope

IntroductionSyncope is a common presentation of sinus node dysfunction (SND). Some patients who receive a permanent pacemaker due to SND do not benefit from it and further diagnostic workup leads to the diagnosis of vasovagal syncope (VVS). The aim of the study was to identify electrophysiological criteria that can be used for identification of patients with SND and concurrent VVS.Material and methodsTransoesophageal atrial pacing (TAP) was performed in 100 patients divided into four groups depending on symptoms and TAP results. Standard electrophysiological parameters of sinus node function and their variability were obtained in the basal state and after pharmacological autonomic blockade (AB).ResultsPatients with concurrent SND and VVS had a greater variability of sinoatrial conduction time assessed by Strauss’ method than patients without incidents of syncope (83.2 ±53.9 vs. 34.1 ±19.6, 47.8 ±33.6 and 32.1 ±22.99). Apart from abnormal sinus node recovery time and second pause, patients with SND had bigger basal state variability of these parameters. In patients with SND and concurrent vasovagal syncope the variability of sinus node recovery time (SNRT), corrected SNRT (cSNRT) and second pause (IIP) decreased after autonomic blockade.ConclusionsPatients with concurrent SND and VVS have distinct electrophysiological features – greater sinoatrial conduction time (SACT) variability and the decrease of SNRT, cSNRT and IIP variability after AB. However, further studies in larger study groups are needed to validate our findings. Transoesophageal atrial pacing is a useful procedure in patients with syncope, especially when the coexistence of more than one cardiac cause is suspected.

Electrophysiology of anterograde right-atrial and left-atrial inputs to the atrioventricular node in patients with atrioventricular nodal re-entrant tachycardia

To study anterograde atrioventricular (A-V) nodal electrophysiological properties through the right-atrial (Ri) and left-atrial inputs (Li) under the pharmacological autonomic blockade (AUB) in patients with slow-fast A-V nodal re-entrant tachycardia (AVNRT) and in controls. Twenty-nine patients with slow-fast AVNRT and 15 control subjects were included. Programmed stimulation with single extrastimulus was performed from the right atrial appendage to test the Ri, and from the posterolateral coronary sinus to test the Li. The AUB was induced with intravenous atropine (0.04 mg/kg) and metoprolol (0.15 mg/kg). The A-V nodal conduction times, refractoriness, discontinuous conduction (≥ 40 ms atrial-His interval 'jump'), and inducibility of AVNRT or reciprocating beats were compared. The A-V nodal conduction times were longer: (i) through the Ri than Li, (ii) in patients than controls, and (iii) in baseline than after AUB--at slow rates in both groups and at fast rates in patients through the right input only (P < 0.05-0.001). A significantly longer slow pathway effective refractory period was demonstrated through the Li than the Ri in patients in baseline (P < 0.05). The discontinuous conduction was demonstrated 94 times in 25 of 29 (83%) patients and 15 times in 6 of 15 (40%) controls (P < 0.01), and was most frequently encountered with the Ri testing. Likewise, inducibility was manifested most frequently with the Ri testing (P = 0.08), and decreased after AUB during this testing only (P = 0.05). The inherent magnitude of discordance of A-V nodal conduction velocity, refractoriness, and parasympathetic modulation between the Ri and Li to the A-V node may play a role in the aetiology of AVNRT.

Impact of Pharmacological Autonomic Blockade on Complex Fractionated Atrial Electrograms

The influence of the autonomic nervous system on the pathogenesis of complex fractionated atrial electrograms (CFAE) during atrial fibrillation (AF) is incompletely understood. This study evaluated the impact of pharmacological autonomic blockade on CFAE characteristics. Autonomic blockade was achieved with propanolol and atropine in 29 patients during AF. Three-dimensional maps of the fractionation degree were made before and after autonomic blockade using the Ensite Navx system. In 2 patients, AF terminated following autonomic blockade. In the remaining 27 patients, 20,113 electrogram samples of 5 seconds duration were collected randomly throughout the left atrium (10,054 at baseline and 10,059 after autonomic blockade). The impact of autonomic blockade on fractionation was assessed by blinded investigators and related to the type of AF and AF cycle length. Globally, CFAE as a proportion of all atrial electrogram samples were reduced after autonomic blockade: 61.6 +/- 20.3% versus 57.9 +/- 23.7%, P = 0.027. This was true/significant for paroxysmal AF (47 +/- 23% vs 40 +/- 22%, P = 0.003), but not for persistent AF (65 +/- 22% vs 62 +/- 25%, respectively, P = 0.166). Left atrial AF cycle length prolonged with autonomic blockade from 170 +/- 33 ms to 180 +/- 40 ms (P = 0.001). Fractionation decreases only in the 14 of 27 patients with a significant (>6 ms) prolongation of the AF cycle length (64 +/- 20% vs 59 +/- 24%, P = 0.027), whereas fractionation did not reduce when autonomic blockade did not affect the AF cycle length (58 +/- 21% vs 56 +/- 25%, P = 0.419). Pharmacological autonomic blockade reduces CFAE in paroxysmal AF, but not persistent AF. This effect appears to be mediated by prolongation of the AF cycle length.

Effects of remifentanil on the cardiac electrophysiologic system under pharmacologic autonomic blockade. Study in an experimental porcine model

Effects of remifentanil on the cardiac electrophysiologic system under pharmacologic autonomic blockade. Study in an experimental porcine model

O exercício físico atenua o déficit autonômico cardíaco induzido pelo bloqueio da síntese do óxido nítrico

BACKGROUND: The nitric oxide (NO) synthesis blockade is characterized by an increase in the cardiac sympathetic activity and the physical training promotes the decrease in the sympathetic activity. OBJECTIVE: We investigated the effect of the NO synthesis blockade on the autonomic cardiovascular control in rats submitted to aerobic exercises during a 10-week period. METHODS: Male Wistar rats were divided in four groups: control rats, treated with chow food and water ad libitum for 10 weeks (CR); control rats, treated with NG-nitro-L-arginine methyl ester (L-NAME) during the last week (CRL); rats trained during 10 weeks on an electrical treadmill (TR); rats trained for 10 weeks and treated with L-NAME during the last week (TRL). The autonomic cardiovascular control was investigated in all groups with the use of a double blockade with methylatropine and propranolol and analysis of variability. RESULTS: The CRL and TRL groups presented hypertension. The CRL group presented tachycardia and predominance of the sympathetic tonus in heat rate (HR) measurement after the pharmacological autonomic blockade. The TR group presented bradycardia and lower intrinsic HR when compared to the others. The evaluation of the HR variability showed lower absolute and normalized values in the low frequency (LF) band in the CRL group. On the other hand, the TRL presented an increase in the LF band in absolute values. The analysis of variability of the systemic arterial pressure (SAP) showed that the CRL and TRL groups presented higher values in the LF band. CONCLUSION: The previous physical exercise prevented the deficit in the autonomic cardiac control induced by the treatment with L-NAME, but did not prevent the increase in the SAP variability.

New squatting test indices are useful for assessing baroreflex sensitivity in diabetes mellitus

AimsThe heart rate (HR) responses after performance of the squatting and standing manoeuvre are thought to be a useful tool to assess autonomic neuropathy in diabetics. Our aim was to develop new simple squatting test indices and to analyse their applicability to the assessment of baroreflex sensitivity (BRS) in patients with diabetes.MethodsTwenty healthy volunteers (mean age 23.2 ± 3.8 years) and 51 patients with diabetes (mean age 55.9 ± 10.6 years) were enrolled in study 1 and study 2, respectively. Each subject stood for 3 min (basal period), then squatted down for 1 min (Sq) and stood up again for 1 min (St). In study 1, the squatting test was performed before and after pharmacological autonomic blockade. In study 2, we measured HR in each period and calculated the difference between basal HR and HRSq (ΔHRSq) and between HRSt and HRSq (ΔHRSt). BRS was also measured using the phenylephrine method in diabetic patients.ResultsIn healthy individuals during autonomic blockade, HR changes were mainly controlled by the vagal tone during squatting and by the sympathetic tone during standing. In diabetic patients, ΔHRSq and ΔHRSt positively correlated (r = 0.86, P < 0.0001) and both ΔHRSq and ΔHRSt significantly correlated with BRS (r = 0.66, P < 0.0001 and r = 0.61, P < 0.0001, respectively).ConclusionsThe new squatting test indices provide useful information for assessing autonomic neuropathy and for identifying diabetic patients at high risk of cardiovascular events.

Selective quantification of the cardiac sympathetic and parasympathetic nervous systems by multisignal analysis of cardiorespiratory variability

Heart rate (HR) power spectral indexes are limited as measures of the cardiac autonomic nervous systems (CANS) in that they neither offer an effective marker of the beta-sympathetic nervous system (SNS) due to its overlap with the parasympathetic nervous system (PNS) in the low-frequency (LF) band nor afford specific measures of the CANS due to input contributions to HR [e.g., arterial blood pressure (ABP) and instantaneous lung volume (ILV)]. We derived new PNS and SNS indexes by multisignal analysis of cardiorespiratory variability. The basic idea was to identify the autonomically mediated transfer functions relating fluctuations in ILV to HR (ILV-->HR) and fluctuations in ABP to HR (ABP-->HR) so as to eliminate the input contributions to HR and then separate each estimated transfer function in the time domain into PNS and SNS indexes using physiological knowledge. We evaluated these indexes with respect to selective pharmacological autonomic nervous blockade in 14 humans. Our results showed that the PNS index derived from the ABP-->HR transfer function was correctly decreased after vagal and double (vagal + beta-sympathetic) blockade (P < 0.01) and did not change after beta-sympathetic blockade, whereas the SNS index derived from the same transfer function was correctly reduced after beta-sympathetic blockade in the standing posture and double blockade (P < 0.05) and remained the same after vagal blockade. However, this SNS index did not significantly decrease after beta-sympathetic blockade in the supine posture. Overall, these predictions were better than those provided by the traditional high-frequency (HF) power, LF-to-HF ratio, and normalized LF power of HR variability.