Cardiac Sympathetic Discharge Research Articles

Relationship of Heart Rate Variability to Sleepiness in Patients with Obstructive Sleep Apnea with and without Heart Failure

Many patients with severe obstructive sleep apnea (OSA) do not complain of excessive daytime sleepiness (EDS), possibly due to increased sympathetic nervous activity (SNA) and accompanying heightened alertness. We hypothesized that in patients with OSA, those without subjective EDS (Epworth Sleepiness Scale, ESS score < 11) would have higher very low frequency (VLF) heart rate variability (HRV) during sleep, reflecting greater sympathetic heart rate modulation than patients with an ESS score ≥ 11. Patients with severe OSA (AHI ≥ 30: 26 with and 65 without heart failure) were divided into those with and without EDS. Heart rate (HR) signals were acquired in stage 2 sleep during periods of recurrent apneas and hypopneas and submitted to coarse graining spectral analysis, which extracts harmonic, neurally mediated contributions to HRV from total spectral power. Because the apnea-hyperpnea cycle entrains muscle SNA at VLF (0 to 0.04 Hz), VLF power was our principal between-group comparison. Subjects without EDS had higher harmonic VLF power (944 ± 839 vs 447 ± 461 msec(2), p = 0.003) than those with EDS, irrespective of the presence or absence of heart failure (1218 ± 944 vs 426 ± 299 msec(2), p = 0.043, and 1029 ± 873 vs 503 ± 533 msec(2), p = 0.003, respectively). ESS scores correlated inversely with VLF power in all (r = -0.294, p = 0.005) and in heart failure subjects (r = -0.468, p = 0.016). Patients with severe OSA but without EDS have higher VLF-HRV than those with EDS. This finding suggests that patients with severe OSA but without EDS have greater sympathetic modulation of HRV than those with EDS that may reflect elevated adrenergically mediated alertness. Taranto Montemurro L; Floras JS; Picton P; Kasai T; Alshaer H; Gabriel JM; Bradley TD. Relationship of heart rate variability to sleepiness in patients with obstructive sleep apnea with and without heart failure.

Takotsubo cardiomyopathy after anti-influenza vaccination: catecholaminergic effects of immune system

Takotsubo cardiomyopathy (TTC) is a well-known condition, which leads to sudden transient regional systolic dysfunction. It mostly affects aging women and is usually precipitated by emotional or physical stress. Despite the tremendous amount of literature on TTC, cardiac sympathetic hyperactivity is the only thing known to be associated with pathogenesis. In our case, an elderly woman presented with an acute episode of TTC 24 hours after anti-influenza vaccination without any obvious stressor for sudden rise in the catecholamine level. Sudden postvaccination change in the cardiac sympathetic discharge is the most likely precipitant of TTC in this case.

Su2115 Altered Activation of Cardiac Sympathetic Discharge and Covariated Brain Region During Colorectal Distention With Corticotropin-Releasing Hormone in Irritable Bowel Syndrome

G A A b st ra ct s plasma ghrelin levels at 2 h after ICV UCN. UCN induces c-fos mRNA and Fos protein expression in the supraoptic nucleus, paraventricular nucleus of hypothalamus (PVN), locus coeruleus, solitary tract nucleus (NTS), and ventrolateral nucleus of medulla oblongata (VLM), known to influence sympathetic outflow. Fos expression in NTS was markedly suppressed by coadministration of RKT (control 84 ± 28, UCN 352 ± 130, UCN + RKT 48 ± 15; P , 0.05). UCN-induced Fos expression in VLM was also suppressed by RKT (control 35 ± 10, UCN 289 ± 94, UCN + RKT 133 ± 27), but not significant (P=0.08). RKT also suppressed UCN-induced c-fos expression in PVN. In contrast, the dorsal motor nucleus involved in vagal outflow did not show any changes in Fos and fos expression by RKT. Conclusions: These data indicate that a) RKT inhibits the activity of the neuron of NTS suggesting that RKT inhibits vagal input from the periphery to central nerves. b) As the result of inhibiton of vagal input, activity of hypothalamic satiety center, PVN is suppressed resulting in the inhibition of the sympathetic outflow from the central nerve to the periphery. RKT may restore disturbed appetite and ghrelin secretion through the restoration of balance of central autonomic nervous system.

Inspiratory muscle training reduces blood pressure and sympathetic activity in hypertensive patients: A randomized controlled trial

BackgroundAutonomic imbalance, characterized by sympathetic hyperactivity and diminished vagal tone, is a known mechanism for essential hypertension. Inspiratory muscle training (IMT) demonstrates beneficial outcomes in a number of cardiovascular populations, which may potentially extend to patients with hypertension. The aim of this study was to further elucidate the effects of IMT on blood pressure and autonomic cardiovascular control in patients with essential hypertension. MethodsThirteen patients with hypertension were randomly assigned to an eight-week IMT program (6 patients) or to a placebo-IMT (P-IMT, 7 patients) protocol. We recorded RR interval for posterior analysis of heart rate variability and blood pressure, by ambulatory blood pressure monitoring (ABPM), before and after the program. ResultsThere was a significant increase in inspiratory muscle strength in the IMT group (82.7±28.8 vs 121.5±21.8 cmH2O, P<0.001), which was not demonstrated by P-IMT (93.3±25.3 vs 106.1±25.3 cmH2O, P>0.05). There was also a reduction in 24-hour measurement of systolic (133.2±9.9 vs 125.2±13.0mmHg, P=0.02) and diastolic (80.7±12.3 vs 75.2±1.0mmHg, P=0.02) blood pressure, as well as in daytime systolic (136.8±12.2 vs 127.6±14.2mmHg, P=0.008) and diastolic (83.3±13.1 vs. 77.2±12.2mmHg, P =0.01) blood pressure in the IMT group. In relation to autonomic cardiovascular control, we found increased parasympathetic modulation (HF: 75.5±14.6 vs. 84.74±7.55 n.u, P=0.028) and reduced sympathetic modulation (LF: 34.67±20.38 vs. 12.81±6.68 n.u; P=0.005). Moreover, there was reduction of cardiac sympathetic discharge (fLF) in IMT group (P=0.01). ConclusionsIMT demonstrates beneficial effects on systolic and diastolic blood pressure as well as autonomic cardiovascular control in hypertensive patients.

The relationship of the lock-step phenomenon and precipitous changes in mean arterial blood pressure

The lock-step phenomenon (LSP) is the occurrence of postganglionic cardiac sympathetic discharge (PCSD) and cortical epileptiform activity (EA) in a time-locked fashion. The relationship between the LSP and precipitous changes in blood pressure (PCBP: > 23 mm Hg in 10 sec) was determined in 9 cats after EA was induced with pentylenetetrazol following pretreatment with phenobarbital (20 mg/kg, i.v.). Electrocorticogram (ECoG), PCSD, lead II EKG, and mean arterial blood pressure (MAP) were monitored. Since an interspike interval of 2.8 sec was frequently found to exist between ECoG spikes when the LSP was present, 4 categories of LSP were defined: LSP absent; stable LSP with 2.8 sec interval; stable LSP without 2.8 sec interval; and unstable LSP with increasing or decreasing rates of discharge. The duration of each LSP pattern and the proportion of time spent in PCBP were determined. A one-way repeated measures ANOVA and the Newman-Keuls post-hoc test showed that a higher mean proportion of time spent in PCBP was associated with the unstable LSP pattern ( P < 0.05). The LSP and associated patterns as related to precipitous changes in MAP are indicators of changes in autonomic function. Autonomic dysfunction with EA, causing cardiac arrhythmias, has been postulated as a cause of sudden unexplained death (SUD) in persons with epilepsy. Thus, an understanding of the autonomic changes, as indicated by PCBP associated with LSP, may contribute to the understanding and prevention of SUD in persons with epilepsy.

Physiological characterization of the renal-sympathetic reflex in rabbits.

In urethane-anesthetized and vagotomized rabbits, electrical stimulation of the afferent renal nerve (RN) elicited reflex changes in renal nerve activity (RNA) and arterial pressure (AP). The responses were attributable mostly to excitation of nonmyelinated afferent fibers, although, in about 30% of the animals, they were contributed slightly by myelinated afferents. In about 70% of rabbits, the peristimulus time histogram (PTH) of RNA following stimulation of the RN consisted of a long-lasting inhibitory (I) component occasionally accompanied, during its recovery phase, by a transient excitatory (E) component. In these animals, tetanic stimulation of the RN resulted in a depressor response, either alone or, if an E component was present in the PTH, followed by a slight pressor response. In the remaining rabbits, the PTH was composed exclusively of an E component and tetanic stimulation caused a pressor response. Stimulation of the RN evoked reflex changes in cardiac sympathetic discharges comparable to that of RNA, whereas the change in cervical sympathetic discharges was much smaller. The sympathetic response remained intact after a total transection of the rostral medulla near the ponto-medullary junction; the I component was even augmented. However, it usually disappeared following a transection at the high cervical cord. Bilateral lesions of the nucl. tractus solitarius (NTS) near the obex failed to appreciably affect the response. Among chemical and mechanical stimuli examined, nociceptive stimulation of the kidney elicited a sympathetic response comparable to that following nerve stimulation. In conclusion, the renal-sympathetic reflex in rabbits (1) originates predominantly from nonmyelinated afferent renal fibers activated effectively by nociceptive stimulation applied to the kidney; (2) depends critically on medullary structures other than the NTS; and (3) evokes changes of the same temporal pattern but of nonuniform magnitude in sympathetic discharges to different organs.

The effect of acute and chronic administration of timolol on cardiac sympathetic neural discharge, arrhythmia, and beta adrenergic receptor density associated with coronary occlusion in the cat

The effect of timolol (5 mg/kg, p.o., b.i.d. 7 or 14 days) on cardiac beta adrenergic receptor density, the times to arrhythmia (AR) and death (D), heart rate, mean arterial blood pressure, and postganglionic cardiac sympathetic neural discharge after acute coronary occlusion in cats was examined. In the control animals, receptor densities in the left and right atria did not differ, but were lower than the right ventricle. Left ventricle and septum receptor densities were higher, with the left ventricle the highest. The importance of the gradation of beta receptors with increasing density from base to apex appears to be its relation to cardiac contractile function. Occlusion in cats not treated with timolol did not alter the cardiac beta receptor densities. After timolol for 7 or 14 days, no occlusion, receptor density increased in left ventricle and septum although the increase was only significant after 14 days. A comparison of the beta adrenergic receptor densities in cats pretreated with timolol for 7 or 14 days with or without occlusion revealed that, in general, a decrease (p>0.05) occurred for the occlusion group. Timolol decreased heart rate and blood pressure prior to occlusion. The mean times to AR and D were not significantly increased by either dosing regimen of timolol, although the trend was for an increase in the time to D after 7 days of timolol and an increase in the time to AR and D after 14 days of timolol. When compared with data obtained in saline cats, chronic timolol produced minimal changes in postganglionic cardiac sympathetic neural discharge. Timolol given chronically (p.o.) or acutely (5 mg/kg, i.v. given 15 min prior to occlusion) also did not prevent the cardiac sympathetic discharge associated with the development of AR. The time to AR and D in the acutely treated cats was increased but not significantly. Since cardiac sympathetic neural discharge increased as blood pressure fell in the control period but did not increase after occlusion in the timolol treated animals, the combination of timolol and occlusion may have modified neural discharge via an action on the baro-receptor mechanism. That chronic administration of timolol produces an effect not present in cats in which only occlusion was done is supported by the observation that chronic treatment produced an occlusion-induced decrease in beta adrenergic receptor density. Since pretreatment with timolol for 7 or 14 days did not increase the time to occlusion-induced AR and D, the data suggest that the clinical protective effect reported for timolol after myocardial infarction seems to be due to a factor or factors other than an action on the autonomic cardiac sympathetic neural discharge or on cardiac beta receptor density.

α2-adrenoceptor-mediated coronary vasoconstriction persists after exhaustion of coronary dilator reserve

The effect of intracoronary administration of the selective α 2-adrenoceptor agonist B-HT 920 on coronary resistance was tested in 14 open-chest dogs before and after exhaustion of coronary dilator reserve. Under both conditions B-HT 920 increased coronary resistance to the same extent: 27 ± 4% before and 32 ± 3% after. Administration of B-HT 920 did not affect cardiovascular haemodynamics significantly, although after exhaustion of coronary dilator reserve left ventricular dP dt max decreased slightly by 12 ± 5%. While efferent cardiac sympathetic discharge remained constant during control conditions it increased by 27 ± 7% when B-HT 920 was administered into a stenotic coronary artery. We conclude that, in contrast to observations made on α 1-adrenoceptors, activation of coronary α 2-adrenoceptors may have deleterious effects after exhaustion of coronary dilator reserve because these receptors mediate a comparable constriction in well- and under-perfused coronary vessels. Thus they are unlikely to favour a redistribution of coronary blood flow into under-perfused myocardial regions. In addition, this unfavourable effect of B-HT 920 on coronary perfusion after coronary dilator reserve has been exhausted may be further exacerbated by an increase in efferent sympathetic discharge.

Failure of methylprednisolone to prevent nonuniform cardiac accelerator nerve discharge associated with coronary occlusion-induced arrhythmia: Evidence against prostaglandin modulation of autonomic cardioaccelerator neural discharge in the anesthetized cat

Postganglionic cardiac sympathetic neural discharge in the minute prior to arrhythmia produced by acute occlusion of the left anterior descending coronary artery was nonuniform, i.e., both increases or decreases occurred. It is hypothesized that the nonuniform neural discharge is transmitted to the heart, causing nonuniform changes in excitability and conduction which produce ventricular arrhythmias. Prostaglandins have been shown to exhibit both arrhythmogenic as well as antiarrhythmic actions. Methylprednisolone (30 or 50 mg/kg, i.v., a known inhibitor of prostaglandin synthesis) was given 30 minutes prior to coronary occlusion of the left anterior descending artery. Both doses of methylprednisolone failed to: exert any effect on the mean postganglionic cardiac sympathetic nerve discharge prior to coronary occlusion; eliminate the nonuniform neural discharge associated with occlusion-induced arrhythmia; increase the time to arrhythmia or death; and decrease the number of cats dying after acute coronary occlusion. Thus, it is hypothesized that methylprednisolone failed to prevent the arrhythmogenic actions of prostaglandins. The failure of methylprednisolone to decrease the time to arrhythmia suggests that, in this study, an antiarrhythmic mechanism for prostaglandins does not exist. The failure of methylprednisolone to prevent the occlusion-induced nonuniform cardiac sympathetic discharge suggests that prostaglandin modulation of the autonomic balance on the heart is not due to a direct action on the postganglionic cardiac sympathetic nerve.

Nature of differential sympathetic discharges in chemoreceptor reflexes

In a study of autonomic reflexes it was found that some produce a generalized, bilaterally uniform response whereas others have an asymmetric or laterality of action. Recordings from vertebral nerve fibers (mainly vasoconstrictors to forelimb muscles), right and left cardiac sympathetics, and renal nerves show that baroreceptors evoke a bilaterally uniform inhibition but chemoreceptors of the carotid sinus and aortic arch initiate a differential discharge. In the chemoreceptor reflex the vagi are activated and bradycardia generally occurs. Vertebral and renal sympathetic fibers increase their activity bilaterally commensurate with the increase in arterial pressure. Sympathetic discharges to the heart, however, are not uniform; they show ipsilateral inhibition and a strong contralateral increase in activity. Stabilization of blood pressure or inactivation of baroreceptors abolishes the ipsilateral inhibition. In isolation, therefore, the chemoreceptor-induced cardiac sympathetic discharge is just quantitatively stronger contralaterally. In the absence of vagi, heart rate changes differ depending on which chemoreceptors are stimulated, because the pacemaker is on the right. Asymmetrical discharges do occur and, in the eventual response to stimulation of chemoreceptors, reflex interactions actually augment the laterality of effects. Peripheral interactions, in the sense that changes effected by one may induce another reflex, are responsible in part for the balances of autonomic activity ultimately seen as the body reacts to stimuli.

Baroreceptor and chemoreceptor influences on sympathetic discharge to the heart

Baroreceptor and chemoreceptor influences in the regulation of sympathetic discharge to the heart were investigated, utilizing electroneurographic recordings from the left inferior cardiac nerve in the cat. Spontaneous discharge patterns exhibited phasic inhibition with the heartbeat and with inflation of the lungs. This was shown to be the consequence of baroreceptor and afferent vagal activity, respectively. Increasing blood pressure with epinephrine or angiotensin II caused marked inhibition of discharge which was abolished by baroreceptor deafferentation. No increase of cardiac sympathetic discharge occurred after the introduction of hypoxic blood into the isolated carotid sinus. Systemic hypoxia caused a marked increase in sympathetic discharge to the heart despite a large increase of systemic blood pressure. This response persisted after denervation of the peripheral chemoreceptors. A similar but less pronounced response to systemic hypercapnia was found. Systemic hypoxia frequently produced bradycardia which could be converted to tachycardia by atropine. This was associated with a large and continuous increase of cardiac sympathetic discharge to the heart. It is concluded that in systemic hypoxia both sympathetic and parasympathetic discharge to the heart is enhanced.