Tonic Vagal Activity Research Articles

The autonomic and nociceptive response to acute exercise is impaired in people with knee osteoarthritis

ObjectivesAn acute bout of exercise typically leads to short term exercise induced hypoalgesia (EIH), but this response is more variable in many chronic pain populations, including knee osteoarthritis (OA) and fibromyalgia (FM). There is evidence of autonomic nervous system (ANS) dysfunction in some chronic pain populations that may contribute to impaired EIH, but this has not been investigated in people with knee OA. The aim of this study was to assess the acute effects of isometric exercise on the nociceptive and autonomic nervous systems in people with knee OA and FM, compared to pain-free controls. MethodsA cross-sectional study was undertaken with 14 people with knee OA, 13 people with FM, and 15 pain free controls. Across two experimental sessions, baseline recordings and the response of the nociceptive and autonomic nervous systems to a 5-min submaximal isometric contraction of the quadriceps muscle was assessed. The nociceptive system was assessed using pressure pain thresholds at the knee and forearm. The ANS was assessed using high frequency heart rate variability, cardiac pre-ejection period, and electrodermal activity. Outcome measures were obtained before and during (ANS) or immediately after (nociceptive) the acute bout of exercise. ResultsSubmaximal isometric exercise led to EIH in the control group. EIH was absent in both chronic pain groups. Both chronic pain groups showed lower vagal activity at rest. Furthermore, people with knee OA demonstrated reduced vagal withdrawal in response to acute isometric exercise compared to controls. Sympathetic reactivity was similar across groups. DiscussionThe findings of reduced tonic vagal activity and reduced autonomic modulation in response to isometric exercise raise the potential of a blunted ability to adapt to acute exercise stress and modulate nociception in people with knee OA. The impairment of EIH in knee OA may, in part, be due to ANS dysfunction.

Direct measurement of vagal tone in rats does not show correlation to HRV

The vagus nerve is the largest autonomic nerve, innervating nearly every organ in the body. “Vagal tone” is a clinical measure believed to indicate overall levels of vagal activity, but is measured indirectly through the heart rate variability (HRV). Abnormal HRV has been associated with many severe conditions such as diabetes, heart failure, and hypertension. However, vagal tone has never been directly measured, leading to disagreements in its interpretation and influencing the effectiveness of vagal therapies. Using custom carbon nanotube yarn electrodes, we were able to chronically record neural activity from the left cervical vagus in both anesthetized and non-anesthetized rats. Here we show that tonic vagal activity does not correlate with common HRV metrics with or without anesthesia. Although we found that average vagal activity is increased during inspiration compared to expiration, this respiratory-linked signal was not correlated with HRV either. These results represent a clear advance in neural recording technology but also point to the need for a re-interpretation of the link between HRV and “vagal tone”.

Effect of deep inspiration on maximum expiratory flow (Vmax) depends on basal bronchomotor tone in young healthy females

The relationship between the effect of deep inspiration on Vmax and basal bronchomotor tone was studied by partial and maximum expiratory flow-volume curve in 16 young healthy females (20-21 years old). Effect of deep inspiration on Vmax (DI index; (PEF25-MEF25)/PEF25) significantly related to percent increase in PEF25 not only by inhalation of ipratropium bromide (r = 0.81, p less than 0.0002) but also by inhalation of salbutamol (r = -0.62, p less than 0.01). Furthermore, day to day variation of DI index significantly related to day to day variation of PEF25 (r = 0.68, p less than 0.005) but not to that of MEF25. These findings suggest that the bronchodilating effect of deep inspiration in young healthy females may depend on intensity of basal bronchomotor tone caused by tonic vagal nerve activity.

Prediction of unexpected sudden death among healthy dogs by a novel marker of autonomic neural activity

Unexpected sudden death among apparently healthy individuals remains a daunting problem. We have previously shown that autonomic modulation of cardiac arrhythmias and autonomic markers, such as baroreflex sensitivity (BRS) and heart rate variability (HRV), carry predictive power after myocardial infarction. We tested the hypothesis that a parameter combining BRS and HRV could predict risk for ventricular fibrillation (VF) during a first ischemic episode in otherwise healthy dogs. In 43 fully instrumented dogs, BRS and frequency domain analysis of HRV were determined, as well as the occurrence (n = 10, high-risk) or absence (n = 33, low-risk) of VF during 2 minutes of myocardial ischemia superimposed on submaximal exercise. TARVA (Tonic and Reflex Vagal Activity), expressed in units, is the parameter resulting from the multiplication of BRS by HF/LF (an index of tonic vagal activity). High-risk dogs had markedly lower TARVA values, reflecting lower cardiac vagal activity, than low-risk animals (12 +/- 5 versus 56 +/- 43 units, P < .001). The area under the receiver-operator characteristic curve for TARVA was 0.96 (95% confidence interval 0.86 to 0.99); its optimal cutoff had a 100% sensitivity and a 88% specificity with positive and negative predictive values of 71% and 100%, respectively. Differences in cardiac autonomic activity, present in healthy dogs, allow prediction of arrhythmic risk during a first ischemic episode. Increased risk is associated with reduced vagal activity. If confirmed in humans, this finding would open the way to the identification of those apparently healthy subjects at risk for sudden cardiac death during their first episode of myocardial ischemia.

Effects of hypercapnia and hypoxemia on respiratory sinus arrhythmia in conscious humans during spontaneous respiration

Normally, at rest, the amplitude of respiratory sinus arrhythmia (RSA) appears to correlate with cardiac vagal tone. However, recent studies showed that, under stress, RSA dissociates from vagal tone, indicating that separate mechanisms might regulate phasic and tonic vagal activity. This dissociation has been linked to the hypothesis that RSA improves pulmonary gas exchange through preferential distribution of heartbeats in inspiration. We examined the effects of hypercapnia and mild hypoxemia on RSA-vagal dissociation in relation to heartbeat distribution throughout the respiratory cycle in 12 volunteers. We found that hypercapnia, but not hypoxemia, was associated with significant increases in heart rate (HR), tidal volume, and RSA amplitude. The RSA amplitude increase remained statistically significant after adjustment for respiratory rate, tidal volume, and HR. Moreover, the RSA amplitude increase was associated with a paradoxical rise in HR and decrease in low-frequency-to-high-frequency mean amplitude ratio derived from spectral analysis, which is consistent with RSA-vagal dissociation. Although hypercapnia was associated with a significant increase in the percentage of heartbeats during inspiration, this association was largely secondary to increases in the inspiratory period-to-respiratory period ratio, rather than RSA amplitude. Additional model analyses of RSA were consistent with the experimental data. Heartbeat distribution did not change during hypoxemia. These results support the concept of RSA-vagal dissociation during hypercapnia; however, the putative role of RSA in optimizing pulmonary perfusion matching requires further experimental validation.

On the genesis of myocardial ischemia

About three quarters of myocardial ischemic events are triggered by the autonomic nervous system. The pathognomonic constellation is a combination of an almost complete withdrawal of tonic vagal activity with increased sympathetic activity. The reduction of tonic vagal activity, which is characteristic for ischemic heart disease, and the acute withdrawal of vagal drive preceding the onset of ischemia are not dependent on coronary artery disease. In this paper, the pathophysiological steps that lead from sympathetic-parasympathetic imbalance to myocardial ischemia shall be discussed. A considerable increase of aerobic glycolysis within the myocardium as a result of the autonomic imbalance is of special importance in this process.

Video-based spatio-temporal maps for analysis of gastric motility in vitro: effects of vagal stimulation in guinea-pigs.

Our aim was to evaluate topographically specific gastric motility changes induced by graded vagal activation. A recently developed method of constructing spatio-temporal maps of motility from video movies was adapted to the in vitro perfused guinea-pig stomach with an intact vagal nerve supply. In the unstimulated preparation, spontaneous activity was low or absent. Bilateral vagal stimulation with frequencies as low as 0.2 Hz triggered weak anally, and in some cases orally, propagating antral contractions at rates of about 5-6 min-1. Upon stimulation with higher frequencies, antral contractions increased significantly in length (starting more proximally) and amplitude, and produced large pressure peaks of up to 25 hPa, with maximal effects at 2-4 Hz. In contrast, the speed of propagation and the interval between peristaltic waves did not change with vagal stimulation at any frequency. Vagal stimulation also produced a significant and frequency-dependent enlargement of the fundus with a maximal effect at 4 Hz. It is concluded that a very low tonic vagal activity is apparently necessary and sufficient to express basic antral motility, while more sustained vagal activity is necessary for high-amplitude gastric contractions and significant sustained fundic relaxation. The constant interval between propagating contractions supports the concept that vagal input impinges on intrinsic enteric neural circuits that have a modulatory role in the myogenic mechanism underlying slow-wave peristalsis, rather than directly on gastric musculature.

The bradycardic agent zatebradine enhances baroreflex sensitivity and heart rate variability in rats early after myocardial infarction.

The bradycardic agent zatebradine (UL-FS 49) reduces heart rate without negative inotropic or proarrhythmic effects. The aim was to experimentally characterize the influence of zatebradine on arterial baroreflex sensitivity (BRS) and heart rate variability (HRV) which are generally considered as estimates of vagal activity and have prognostic value in patients after myocardial infarction (MI). Conscious rats were studied 3 days after left coronary artery ligation or sham-operation (SH). BRS was determined by linear regression analysis of RR-interval and mean arterial pressure changes evoked by intravenous (i.v.) injections of methoxamine and nitroprusside. HRV at rest was calculated from high-resolution electrocardiogram-recordings. In MI-rats heart rate was similar to SH-rats, mean arterial pressure was lower and both BRS and HRV were markedly reduced. Zatebradine (0.5 mg/kg i.v.) reduced heart rate in MI-rats from 400 +/- 15 to 350 +/- 19 and in SH-rats from 390 +/- 19 to 324 +/- 6 beats/min without changing mean arterial pressure. Both BRS and HRV were restored in MI- and further increased in SH-rats by the drug. Effects of 0.05, 0.5 and 5 mg/kg zatebradine revealed a dose-dependency of heart rate reduction. The lowest dose enhanced reflex bradycardia despite little effect on heart rate and lack of effect on both reflex tachycardia and HRV. Both BRS and HRV are reduced in rats early after MI, indicating a depressed reflex and tonic vagal activity. Treatment with zatebradine enhances both BRS and HRV. These data suggest that the drug has both peripheral and central effects, leading to an increase of vagal control of heart rate.

Cardiac autonomic tone and its relation to nonsustained ventricular tachyarrhythmias in idiopathic dilated cardiomyopathy.

In contrast to postinfarct patients, little is known about cardiac autonomic tone and its relation to spontaneous ventricular tachyarrhythmias in idiopathic dilated cardiomyopathy (IDC). Both heart rate variability (HRV) and baroreflex sensitivity (BRS) are indices of autonomic innervation of the heart. The aim of the present study was to determine the relation between cardiac autonomic tone assessed by HRV and BRS and spontaneous nonsustained ventricular tachycardia (NSVT) on Holter in a large patient population with IDC. 24-h digital Holter recordings including HRV analysis and BRS testing were prospectively performed in 137 patients with IDC and preserved sinus rhythm. Mean age was 48 +/- 12 years, and mean left ventricular (LV) ejection fraction was 32 +/- 9%. The HRV analysis on Holter included the mean RR interval (RRm), the standard deviation of all normal RR intervals (SDNN), the square root of the mean of the squared differences between adjacent normal RR intervals (rMSSD), and the proportion of adjacent normal RR intervals differing more than 50 ms (pNN50). Testing for BRS was performed noninvasively using the phenylephrine method. Of 137 study patients, 42 (31%) had spontaneous NSVT on 24-h Holter. Compared with patients without NSVT, patients with NSVT on Holter had a higher New York Heart Association (NYHA) functional class (NYHA III: 40 vs. 18%, p < 0.01), a lower ejection fraction (29 +/- 9 vs. 34 +/- 9%, p = 0.01), and an increased LV end-diastolic diameter (69 +/- 8 mm vs. 66 +/- 7 mm, p = 0.03). The HRV variables rMSSD, pNN50, RRm, and BRS did not differ significantly between patients with and without spontaneous NSVT. Only SDNN on Holter was slightly lower in patients with versus without NSVT (106 +/- 45 vs. 121 +/- 46 ms, p = 0.08). Patients with IDC and spontaneous NSVT on Holter are characterized by a higher NYHA functional class, a lower LV ejection fraction, an increased LV end-diastolic diameter, and a tendency toward a lower SDNN value compared with patients without NSVT. The remaining measures of HRV including rMSSD and pNN50 reflecting primarily tonic vagal activity, as well as BRS reflecting predominantly reflex vagal activity, were similar in patients with and without NSVT. The prognostic significance of these findings in patients with IDC is currently under investigation in the Marburg Cardiomyopathy Study (MACAS) at our institution.

Baroreflex sensitivity and heart rate variability in conscious rats with myocardial infarction.

The baroreflex sensitivity (BRS) and the heart rate variability (HRV) were studied in conscious rats after myocardial infarction (MI; induced by coronary artery ligation) and after sham operation (SH). BRS was determined by linear regression of R-R interval vs. arterial pressure changes induced by nitroprusside or methoxamine (intravenous bolus). HRV was calculated from 3-min electrocardiogram recordings. Left ventricular end-diastolic pressure and plasma atrial natriuretic peptide were increased after MI; plasma norepinephrine and basal heart rate (HR) remained unchanged. At 3 and 28 days after MI, BRS was reduced as indicated by decreased reflex bradycardia (RB) (MI, 0.66 +/- 0.13 and 0.78 +/- 0.07 ms/mmHg; SH, 1.27 +/- 0.16 and 1.48 +/- 0.14 ms/mmHg, respectively; P < 0.05 MI vs. SH). At 56 days after MI, BRS was normalized. RB was unaffected by atropine 3 and 28 days after MI but reduced in all other groups. The increase of basal HR by atropine 3 and 28 days after MI was less than in all other groups. HRV (SD of mean N-N interval, coefficient of variance, low- and high-frequency power; studied at 28 and 56 days) was similar in all groups. It is concluded that BRS is transiently depressed in rats with left ventricular dysfunction after MI probably due to a reduced reflex vagal activity. Even though basal HR and HRV are unchanged after MI, a temporary attenuation of tonic vagal activity is unmasked after autonomic blockade.

Triazolam and melatonin effects on cardiac autonomic function during sleep.

After benzodiazepine (BDZ) administration, a decrease in cardiac vagal tone has been described during wakefulness, but data on cardiac autonomic function during sleep are lacking. Melatonin (MLT), reported to have hypnotic properties, caused an increase in vagal tone in animals. The aim of this study was to evaluate heart rate (HR) variability during sleep after a single bedtime dose of triazolam (TRI, 0.125 mg) and MLT (100 mg) in six healthy young subjects. We evaluated tonic (vagal activity) HR modifications in relation to sleep as well as phasic (sympathetic activity) HR modifications in relation to spontaneous body movements during rapid-eye-movement (REM) and non-REM (NREM) sleep. No significant change in sympathetic activity was observed after TRI and MLT in comparison with placebo, whereas TRI caused a significant decrease in vagal tone during sleep. Our nocturnal study seems to confirm previous diurnal findings about a decrease in vagal tone by BDZs.

976-12 Reduced Reflex Vagal Activity in Patients with AV Nodal Reentrant Tachycardia Compared to Patients with Atrioventricular Reentrant Tachycardia

Decreased heart rate variability, a manifestation of reduced tonic vagal activity. has been reported following radiofrequency catheter ablation (RFCA) for AV nodal reentrant tachycardia (AVNRT). Disruption of parasympathetic fibers in the posteroseptal region is the proposed mechanism. Baroreflex sensitivity (BRS). an index of reflex vagal activity. has not been evaluated in patients with AVNRT. We studied BRS prior to and immediately following RFCA in 20 patients with AVNRT(age 13–65 years, mean 42; 15 females. 5 males). Fourteen patients with atrioventricular reentrant tachycardia (AVRT) and free wall accessory pathways (age 14–46 years. mean 25; 6 females. 8 males) were evaluated as controls (RFCA site far from posteroseptal region I. BRS (msec/mmHg) was assessed with continuous femoral artery blood pressure (BP) and ECG recordings during the bolus administration of phenylephrine (400 μg). BRS was calculated as the slope of the change in cycle length vs the change in systolic BP during the first sustained rise in BP. At baseline. prior to RFCA. mean BRS for patients with AVNRT was significantly less than for patients with AVRT (8.3 ± 5.9 vs 22.1 ± 10.3; P &lt; 0.0002). This difference remained significant when controlled for age (p &lt; 0.0002) and male gender (p &lt; 0.0003). but not for female gender (p &lt; 0.09). Following RFCA there was no significant change in BRS for patients with AVNRT (9.3 ± 7.6) or AVRT (17.3 ± 9.6) compared to pre-RFCA values. This comparison remained insignificant when controlled for age or gender. These results suggest that in the baseline state, patients with AVNRT have lower reflex vagal activity than patients with AVRT. Reduced reflex vagal activity may contribute to the development of sustained AVNRT in patients with dual AV nodal physiology. RFCA did not alter BRS in either patient group.

Baroreflex Sensitivity

Arterial baroreceptors play an important role among the large number of physiological mechanisms governing the adjustment of cardiovascular system to several surrounding conditions. By baroreceptor stimulation, arterial pressure changes can modulate both sympathetical and vagal activity and, as a consequence, heart rate, contractility and vascular resistance. In the last years, many experimental and clinical observations have shown that ischemic heart disease and heart failure can change baroreceptor reflex sensitivity and cause excessive or inappropriate activity of the sympathetic system. Several methods have been developed to measure baroreceptor sensitivity by estimating the extent of change in heart rate following blood pressure oscillations being them spontaneous or brought about by application of pharmacological or mechanical stimuli. Under normal clinical conditions these measurements can be taken as the ability to activate a sympathetic answer (hypotension) or a parasympathetic one (hypertension), with the interplay of tonic vagal or sympathetic activity. The methodology most extensively used in the clinical setting relies on intravenous administration of phenylephrine, a pure alpha-agonist drug that activates arterial baroreceptors and leads to a reflex bradycardia, which can be measured as RR interval prolongation. Baroreflex sensitivity is quantified in ms of RR interval prolongation for each mmHg of arterial pressure increase. Compared to values obtained in normal subjects (average 15 ms/mmHg) baroreflex sensitivity is significantly depressed in post-infarction patients and in patients with heart failure. The application of a mechanical stimulus is carried out by means of a positive or negative pneumatic pressure through a collar around the neck. A decrease in neck chamber pressure, by stretching carotid receptors, is sensed as an arterial pressure increase and activates reflex bradycardia at the sinus node. Finally, the analysis of spontaneous oscillations of arterial pressure and heart rate can also provide information about baroreflex control of the cardiovascular system: indeed, even small physiological variations in arterial pressure can evoke a reflex heart rate response brought about by arterial baroreceptor. The potential clinical interest of these measurements (completely non-invasive) must be still studied in large populations to define both range of normality and prognostic significance.

Single cardiac vagal fiber activity, acute myocardial ischemia, and risk for sudden death.

Experimental and clinical evidence indicates that high risk for sudden death is significantly correlated with post-myocardial infarction depression in two "markers" of vagal activity, heart rate variability and baroreflex sensitivity. The present experiments were designed to answer some of the questions generated by those findings. In 33 anesthetized cats, the neural activity of single cardiac vagal efferent fibers was recorded in control conditions and after injection of phenylephrine (n = 33), before and during a 1-hour coronary artery occlusion (CAO) (n = 17), and before and after removal of the left stellate ganglion (n = 16). In the first minute after CAO, vagal activity increased by 35% from 1.66 +/- 0.37 to 2.57 +/- 0.62 impulses/sec (p less than 0.01); despite a slight decline, it remained for the entire CAO above the control values, to which it returned after CAO release. Of 17 cats, ventricular fibrillation occurred in nine (susceptible) and eight survived (resistant). Resistant and susceptible cats had different reflex vagal responses to CAO. Whereas the resistant cats had a 48% (p less than 0.01) increase by the second minute of CAO, susceptible cats had no change (-18%, p = NS) in vagal activity. These differences were independent of blood pressure changes. The increase in vagal efferent activity in response to the blood pressure rise induced by phenylephrine (baroreceptive reflex) was more marked in the resistant cats compared with the susceptible cats (+246 +/- 66% versus +80 +/- 14%, p less than 0.025). Just before the injection of phenylephrine, vagal activity was not different between resistant and susceptible cats (1.58 +/- 0.35 versus 1.48 +/- 0.30 impulses/sec, p = NS). In 16 cats, left stellectomy increased cardiac vagal efferent activity by 75% (p less than 0.01), and the reflex vagal activation secondary to phenylephrine was further enhanced (from 2.2 +/- 0.4 to 4.7 +/- 0.7 impulses/sec, p less than 0.001). These data demonstrate that 1) cardiac vagal efferent activity increases in response to acute myocardial ischemia--much more so among the animals destined to survive, 2) before CAO, susceptible and resistant animals can be identified by the vagal response to blood pressure increase (assessed clinically by baroreflex sensitivity) and not by tonic vagal activity (assessed clinically by heart rate variability), and 3) the findings with left stellectomy support the hypothesis that vagal activity decreases after myocardial infarction because of an increase, secondary to abnormal stretch of the cardiac mechanoreceptors, in cardiac sympathetic afferent traffic, which exerts a tonic restraint on vagal outflow.

Effect of atenolol and diltiazem on heart period variability in normal persons

Several time and frequency domain measures of heart period variability are reduced 1 to 2 weeks after myocardial infarction, and a reduced standard deviation of normal RR intervals over a 24 h period (SDNN) is associated with increased mortality. The predictive accuracy of heart period variability may be reduced by drugs used to treat patients after myocardial infarction. Accordingly, a randomized, three period, placebo-controlled, crossover (Latin square) design was used to determine the effect of atenolol and diltiazem on time and frequency measures of heart period variability calculated from 24 h continuous electrocardiographic recordings during treatment with atenolol, diltiazem and placebo in 18 normal volunteers. During atenolol treatment, the 24 h average normal RR (NN) interval increased 24% (p less than 0.001). The three measures of tonic vagal activity were significantly increased (p less than 0.001) during atenolol treatment: percent of successive normal RR intervals greater than 50 ms = 69%, root mean square successive difference of normal RR intervals = 61% and high frequency power in the heart period power spectrum = 84%. Low frequency power also increased 45% (p less than 0.01), indicating that this variable also is an indicator of tonic vagal activity over 24 h. Diltiazem had no significant effect on the 24 h average NN interval or on any measure of heart period variability. The decreased mortality rate after myocardial infarction associated with beta-adrenergic blocker but not calcium channel blocker therapy may be attributed in part to an increase in vagal tone caused by beta-blockers.

Effect on breathing of raising end-expiratory lung volume in sleeping laryngectomized man

In animals, tonic vagal activity from lung receptors provides a means by which changes in end-expiratory lung volume can influence respiratory timing. We wished to examine whether increasing the end-expiratory lung volume within the tidal volume range had a similar effect in man. In order to minimize behavioral influences on breathing, the study was performed in subjects during deep non-rapid eye movement sleep. Five laryngectomized subjects were chosen for the study since their permanent tracheal stomata allow simple, airtight connection to respiratory apparatus and avoided problems with glottic closure. During EEG-documented sleep, end-expiratory volume was increased by up to 350 ml with the addition of expiratory threshold loads of 1 to 10 cm H 2O. End-expiratory volume increased linearly with expiratory pressure. Inspiratory and expiratory times (T I and T E) were not affected by increases in end-expiratory volume. Tidal volume (V T) was decreased such that end-inspiratory volume remained unchanged. The decrease in V T may result from a reduction in inspiratory muscle efficiency at a higher lung volume. The results of the study provide no evidence that tonic vagal afferent information from the lungs is important in controlling respiratory rhythm within the tidal volume range in man when behavioral control of breathing is minimized.

Comparison of baroreflex sensitivity and heart period variability after myocardial infarction

In animals, baroreflex sensitivity is inversely related to the likelihood of ventricular fibrillation during myocardial ischemia. After myocardial infarction in human patients, reduced baroreflex sensitivity is associated with increased mortality. A reduced standard deviation of normal RR intervals over a 24 h period is also associated with reduced survival after myocardial infarction. Therefore, 32 normotensive men who had survived their first myocardial infarction were studied to define the relation between baroreflex sensitivity assessed with phenylephrine injection and three Hotter electrocardiographic measures of tonic vagal activity: the percent of successive normal RR intervals >50 ms, the root mean square successive difference of normal RR intervals and the power in the high frequency energy of the normal RR interval power spectrum.Correlations among the Holter measures of heart period variability were ≥0.94, indicating that these measures are so strongly correlated that any one of them can be used to represent the others. Baroreflex sensitivity showed weaker correlations with the three Holter variables (0.57 to 0.63), indicating that the Holter measures did not accurately predict baroreflex sensitivity. Baroreflex sensitivity showed a stronger correlation with the three Hotter variables during the night than during the day. Baroreflex sensitivity and tonic vagal activity reflected by Holter variables were reduced more in patients with inferior myocardial infarction than in those with anterior infarction. The relative utility of baroreflex sensitivity and Holter measures of tonic vagal activity in predicting sudden cardiac death after myocardial infarction needs to be evaluated in a large prospective study.

Comparison of time- and frequency domain-based measures of cardiac parasympathetic activity in Holter recordings after myocardial infarction

The standard deviation of normal RR intervals predicts mortality after acute myocardial infarction independently of left ventricular function and ventricular arrhythmias. 1 Myers et al 2 suggested that this measure of heart period variability is a broad-band measure composed of high and low frequency components, and suggested that patients with malignant arrhythmias have reduced power in the high frequency band of the heart period or heart rate power spectrum. The high frequency band of the heart rate power spectrum reflects vagally mediated respiratory sinus arrhythmia. 3–5 Also, 2 time domain measures—the percent of absolute differences between successive normal RR intervals that exceed 50 ms (pNN50) and the root mean square successive difference (r-MSSD)—have been used as measures of tonic vagal activity. 6 The objective of this study was to determine the strength of association among 3 measures of tonic vagal activity: the high frequency band (0.15 to 0.50 Hz) in the heart period power spectrum, pNN50 and r-MSSD. We expected strong correlations among these 3 variables, and hoped that the correlations would be strong enough to permit their interchangeable use for assessing tonic vagal activity in long duration electrocardiographic recordings. We expected weaker correlations of these 3 measures with measures of total heart rate or heart period variability, such as the standard deviation of normal RR intervals or the total power in the heart period power spectrum.

Effects of tonic vagal input on breathing pattern in newborn rabbits.

Respiratory effects of positive and negative pressure breathing were studied in 1- and 4-day-old rabbit pups anesthetized with ketamine (50 mg/kg, im) and acepromazine (3 mg/kg, im). We recorded tidal volume (VT), tracheal pressure (Ptr), and integrated diaphragmatic EMG (DiEMG). Inspiratory (TI) and expiratory time (TE) were measured from the records of DiEMG. During breathing with increased Ptr by 1 or 2 cmH2O, VT, minute ventilation (VE), and respiratory rate (f) decreased. Changes in f relied on a TE prolongation. Neither DiEMG nor its rate of rise (DiEMGt) were affected. Except for VT decrease during positive Ptr, all other effects disappeared after vagotomy. Our results indicate that an increase in tonic vagal activity interacts with the mechanisms controlling TE and has no effect on depth and duration of inspiration. When Ptr decreased by 1 and 2 cmH2O, VE increased due to an increase in f. Increase in f relied on shortening of both TI and TE; the TE effect being more pronounced. DiEMG and DiEMGt also increased. Adverse effects of lung deflation and vagotomy strongly suggest that the respiratory reflex stimulation due to decrease in Ptr does not rely on inhibition of the slowly adapting stretch receptor activity. Therefore other excitatory vagal inputs must be responsible for this response. We propose two vagally mediated inputs: the irritant and/or the cardiac receptors.

Effect of extragastric and truncal vagotomy on pancreatic secretion in the dog.

In four dogs with chronic pancreatic and gastric fistulas, dose-response studies of pancreatic bicarbonate and protein secretion were done with intravenous infusions of secretin, octapeptide of cholecystokinin (OP-CCK), and 2-deoxyglucose (2-DG). The pancreatic response to a meal and to duodenal perfusion of graded concentrations of HCl, sodium oleate, and tryptophan were also studied. These observations were repeated after division of both the hepatic and celiac vagal branches to produce extragastric vagotomy, and subsequently after transthoracic truncal vagotomy. The responses to secretin, OP-CCK, and to duodenal perfusion of HCl were either unaltered or only slightly decreased by either extragastric or truncal vagotomy. Basal pancreatic secretion and the responses to duodenal perfusion of oleate and tryptophan were markedly depressed by extragastric vagotomy. These findings indicate that tonic vagal activity contributes to basal pancreatic secretion but has little effect on the response of the pancreas to secretin or CCK or on the release of secretin from the intestine. The decreased pancreatic response to intestinally perfused oleate and tryptophan seen after extragastric vagotomy could be caused either by interruption of reflex paths between gut and pancreas or by interference with CCK release. Extragastric vagotomy reduced pancreatic responses to a meal and to 2-DG and subsequent truncal vagotomy caused still further reduction, possibly, at least in part, by depressing release of antral gastrin.