Vagal Discharge Research Articles

Thermal acclimation and acute temperature effects on cardiac barostatic reflexes in rainbow trout (Oncorhynchus mykiss)

Acute warming raises the metabolism of fish, which is matched by increased heart rate. However, thermal acclimation may reduce heart rate through combinations of lowered intrinsic pacemaker rate and increased inhibitory vagal tone. This could affect the baroreflex, which regulates arterial blood pressure through heart rate changes via altered vagal tone. Using pharmacological tools, we assessed autonomic tones and baroreflex regulation of heart rate in rainbow trout (Oncorhynchus mykiss) at 11 °C, and after acute (24 h, 17°Cacute) or chronic (>7 weeks, 17°Cchronic) warming to 17 °C. We hypothesised that warm acclimation would manifest as reduced heart rate and elevated vagal tone in 17°Cchronic trout relative to 11 °C and 17°Cacute trout, which would increase baroreflex gain and the scope for fH increase through vagal release during hypotension. Compared to 11 °C, the 17°Cacute group exhibited slightly higher heart rate (Q10 = 1.5) and a strong trend for elevated vagal tone (54%). Surprisingly, however, routine heart rate was unaltered by warm acclimation (Q10 = 1.6), while intrinsic heart rate and vagal tone (22%) declined. Consequently, baroreflex sensitivity to reduced blood pressure was elevated in the 17°Cacute group but returned towards 11 °C conditions in the 17°Cchronic group. Atropine abolished nearly all chronotropic changes. Bradycardic responses to hypertension and cardiac adrenergic tone were unaltered across temperature treatments. The lack of a clear acclimation effect on routine heart rate in the present study is likely explained by a seasonal effect as the experiments were performed in early winter. Nonetheless, we conclude that baroreflex sensitivity in trout is thermally plastic; the heightened baroreflex sensitivity to hypotension following acute warming likely serves to safeguard tissue oxygen delivery as metabolism is elevated, while the reduced baroreflex sensitivity observed with warm acclimation may be linked to a pronounced metabolic down-regulation.

Immunomodulation of innate immunity by brachial plexus blockade: a crossover study

The autonomic nervous system regulates innate immune function in response to afferent pain signals from injured tissue.1 During acute inflammation, vagal release of acetylcholine suppresses the expression of CD11b, a surface integrin regulating neutrophil transmigration to injured tissue. Whether regional anaesthesia modulates innate neuroimmune control has not been tested. We tested the hypothesis that brachial plexus block modulates the innate immune response to ischaemic tissue injury.

Neuromodulation of innate immunity by remote ischaemic conditioning in humans: Experimental cross-over study

Experimental animal studies on the mechanisms of remote ischaemic conditioning (RIC)-induced cardioprotection against ischaemia/reperfusion injury demonstrate involvement of both neuronal and humoral pathways. Autonomic parasympathetic (vagal) pathways confer organ protection through both direct innervation and/or immunomodulation, but evidence in humans is lacking. During acute inflammation, vagal release of acetylcholine suppresses CD11b expression, a critical β2-integrin regulating neutrophil adhesion to the endothelium and transmigration to sites of injury. Here, we tested the hypothesis that RIC recruits vagal activity in humans and has an anti-inflammatory effect by reducing neutrophil CD11b expression. Participants (age:50 ​± ​19 years; 53% female) underwent ultrasound-guided injection of local anaesthetic within the brachial plexus before applying 3 ​× ​8 min cycles of brachial artery occlusion using a blood pressure cuff (RICblock). RIC was repeated 6 weeks later without brachial plexus block. Masked analysers quantified vagal activity (heart rate, heart rate variability (HRV)) before, and 10 ​min after, the last cycle of RIC. RR-interval increased after RIC (reduced heart rate) by 40 ​ms (95% confidence intervals (95%CI):13–66; n ​= ​17 subjects; P ​= ​0.003). RR-interval did not change after brachial plexus blockade (mean difference: 20 ​ms (95%CI:-11 to 50); P ​= ​0.19). The high-frequency component of HRV was reduced after RICblock, but remained unchanged after RIC (P ​< ​0.001), indicating that RIC preserved vagal activity. LPS-induced CD16+CD11b+ expression in whole blood (measured by flow cytometry) was reduced by RIC (3615 median fluorescence units (95%CI:475-6754); P = 0.026), compared with 2331 units (95%CI:-3921 to 8582); P = 0.726) after RICblock.These data suggest that in humans RIC recruits vagal cardiac and anti-inflammatory mechanisms via ischaemia/reperfusion-induced activation of sensory nerve fibres that innervate the organ undergoing RIC.

Simultaneous cardiac and respiratory inhibition during seizure precedes death in the DBA/1 audiogenic mouse model of SUDEP.

This study was designed to evaluate cardiac and respiratory dysfunction in a mouse model of sudden unexpected death in epilepsy i.e., SUDEP. We simultaneously monitored respiration via plethysmography and the electrocardiogram via telemetry before, during, and after an audiogenic seizure. DBA/1 mice responded to an acoustic stimulus with one or two cycles of circling and jumping before entering a clonic/tonic seizure. This was followed by death unless the mice were resuscitated by mechanical ventilation using room air. During the initial clonic phase, respiration declined and cardiac rhythm is slowed. By the tonic phase, respiration had ceased, atrial P-waves were absent or dissociated from the QRS complex, and heart rate had decreased from 771±11 to 252±16 bpm. Heart rate further deteriorated terminating in asystole unless the mice were resuscitated at the end of the tonic phase which resulted in abrupt recovery of P-waves and a return to normal sinus rhythm, associated with gasping. Interestingly, P-waves were preserved in the mice treated with methylatropine during the pre-ictal period (to block parasympathetic stimulation) and heart rate remained unchanged through the end of the tonic phase (765±8 vs. 748±21 bpm), but as in control, methylatropine treated mice died from respiratory arrest. These results demonstrate that a clonic/tonic seizure in the DBA/1 mouse results in abrupt and simultaneous respiratory and cardiac depression. Although death clearly results from respiratory arrest, our results suggest that seizure activates two central nervous system pathways in this model—one inhibits respiratory drive, whereas the other inhibits cardiac function via vagal efferents. The abrupt and simultaneous recovery of both respiration and cardiac function with mechanical ventilation within an early post-ictal timeframe shows that the vagal discharge can be rapidly terminated. Understanding the central mechanism associated with the abrupt cardiorespiratory dysfunction and equally abrupt recovery may provide clues for therapeutic targets for SUDEP.

Association of stress with heart rate variability in different phases of the menstrual cycle

Background: The menstrual cycle signifies a fine balance of female sexual hormones and integrity of hypothalamohypophyseal-gonadal axis, during reproductive age. Many women experience unpredictable menstruation when they encounter various kinds of stress situations that often interrupt the normal cycle. Heart rate variability is the quantitative measure of autonomic tone. Aims and Objectives: The present study is aimed to observe the effect of stress and autonomic balance in different menstrual cycle phases of young adolescent female medical students. Materials and Methods: It is a cross-sectional study where 50 young medical female students aged between 18 and 25 years were recruited and their demographic features were measured. All the study procedures except cortisol collection (early morning) were done in between 9 AM and 11 PM after 1–2 h of light breakfast. Results: All parameters were measured in premenstrual phase (25th ± 4 days) and postmenstrual phase (10th ± 5 days). Low frequency (LF) increases from 0.07 ± 0.009Hz to 0.08 ± 0.005 Hz (P – 0.01). However, high frequency decreases from 0.27 ± 0.02Hz to 0.26 ± 0.01Hz (P - 0.01). The time domain parameters SDNN 59.11 ± 24.1 increase to 74.34 ± 52.7 (P – 0.04). STD HR significantly reduced from 69.58 ± 12.1 to 35.36 ± 16.4 (P - 0.01). RMSSD increased from 47.98 ± 5.5 to 75.24 ± 14.6 (P – 0.02). However, NN50 reduced from 64.65 ± 12.8 to 48.52 ± 12.4 statistically significant (P – 0.05). However, there is no significant change in cortisol levels in both phases. Conclusion: The results suggest that there is a significant difference in sympathovagal balance between pre- and post-menstrual phases. LF indicates that vagal discharge is more in premenstrual phase, whereas sympathetic tone increases in postmenstrual phase.

Electro-acupuncture regulates the cholinergic anti-inflammatory pathway in a rat model of chronic obstructive pulmonary disease

ObjectiveAcupuncture has a definite therapeutic effect on chronic obstructive pulmonary disease (COPD), and the cholinergic anti-inflammatory pathway (CAP) has been shown to be involved in regulation of inflammation. In this study, we investigated whether electro-acupuncture (EA) affects the CAP in COPD. MethodsSprague–Dawley rats were induced into COPD through exposure to cigarette smoke combined with lipopolysaccharide. EA treatment was applied at Zusanli (ST36) and Feishu (BL13) points for 30 min/d for 7 d. Seventy-two rats were randomly divided into six study groups, including normal, normal + EA, normal + α-bungarotoxin (α-BGT) (the antagonist of the nicotinic acetylcholine receptor α7 subunit (α7nAChR)) + EA, COPD, COPD + EA, and COPD + α-BGT + EA. Lung function, pathology and vagus nerve discharge were tested. The levels of acetylcholine (ACh), acetylcholinesterase (AChE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) and lung tissue were measured by enzyme-linked immunosorbent assay. The mRNA and protein expression and immunoreactivity of α7nAChR and its postreceptor inflammation signal pathway, including janus kinase 2 (JAK2), signal transducers and activators of transcription 3 (STAT3), nuclear factor-κB (NF-κB), were observed by quantitative reverse transcription-polymerase chain reaction, Western blot and immunohistochemistry. ResultsCompared with normal rats, there were a significant decline in lung function and discharge of the vagus nerve (P < 0.01), a marked sign of lung inflammation and an increase of ACh, AChE, IL-6 and TNF-α level in BALF or lung tissue (P < 0.05, P < 0.01) and higher expression of α7nAChR, JAK2, STAT3 and NF-κB (P < 0.05, P < 0.01) in the COPD rats. In rats receiving EA, the lung function and vagal discharge were enhanced (P < 0.01), lung inflammation was improved and the levels of ACh, AChE, IL-6 and TNF-α were decreased (P < 0.01). Further, the expression of α7nAChR, JAK2, STAT3 and NF-κB was downregulated (P < 0.05, P < 0.01). However, the above effects of EA were blocked in rats injected with α-BGT (P < 0.01). ConclusionEA treatment can reduce the lung inflammatory response and improve lung function in COPD, which may be related to its involvement in the regulation of CAP.

Pyridostigmine protects against cardiomyopathy associated with adipose tissue browning and improvement of vagal activity in high-fat diet rats

Obesity, a major contributor to the development of cardiovascular diseases, is associated with an autonomic imbalance characterized by sympathetic hyperactivity and diminished vagal activity. Vagal activation plays important roles in weight loss and improvement of cardiac function. Pyridostigmine is a reversible acetylcholinesterase inhibitor, but whether it ameliorates cardiac lipid accumulation and cardiac remodeling in rats fed a high-fat diet has not been determined. This study investigated the effects of pyridostigmine on high-fat diet-induced cardiac dysfunction and explored the potential mechanisms. Rats were fed a normal or high-fat diet and treated with pyridostigmine. Vagal discharge was evaluated using the BL-420S system, and cardiac function by echocardiograms. Lipid deposition and cardiac remodeling were determined histologically. Lipid utility was assessed by qPCR. A high-fat diet led to a significant reduction in vagal discharge and lipid utility and a marked increase in lipid accumulation, cardiac remodeling, and cardiac dysfunction. Pyridostigmine improved vagal activity and lipid metabolism disorder and cardiac remodeling, accompanied by an improvement of cardiac function in high-fat diet-fed rats. An increase in the browning of white adipose tissue in pyridostigmine-treated rats was also observed and linked to the expression of UCP-1 and CIDEA. Additionally, pyridostigmine facilitated activation of brown adipose tissue via activation of the SIRT-1/AMPK/PGC-1α pathway. In conclusion, a high-fat diet resulted in cardiac lipid accumulation, cardiac remodeling, and a significant decrease in vagal discharge. Pyridostigmine ameliorated cardiomyopathy, an effect related to reduced cardiac lipid accumulation, and facilitated the browning of white adipose tissue while activating brown adipose tissue.

Long-term administration of pyridostigmine attenuates pressure overload-induced cardiac hypertrophy by inhibiting calcineurin signalling.

Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload‐induced cardiac hypertrophy and identify the underlying mechanisms. Rats were subjected to either sham or constriction of abdominal aorta surgery and treated with or without pyridostigmine for 8 weeks. Vagal activity and cardiac function were determined using PowerLab. Cardiac hypertrophy was evaluated using various histological stains. Protein markers for cardiac hypertrophy were quantitated by Western blot and immunoprecipitation. Pressure overload resulted in a marked reduction in vagal discharge and a profound increase in cardiac hypertrophy index and cardiac dysfunction. Pyridostigmine increased the acetylcholine levels by inhibiting acetylcholinesterase in rats with pressure overload. Pyridostigmine significantly attenuated cardiac hypertrophy based on reduction in left ventricular weight/body weight, suppression of the levels of atrial natriuretic peptide, brain natriuretic peptide and β‐myosin heavy chain, and a reduction in cardiac fibrosis. These effects were accompanied by marked improvement of cardiac function. Additionally, pyridostigmine inhibited the CaN/NFAT3/GATA4 pathway and suppressed Orai1/STIM1 complex formation. In conclusion, pressure overload resulted in cardiac hypertrophy, cardiac dysfunction and a significant reduction in vagal discharge. Pyridostigmine attenuated cardiac hypertrophy and improved cardiac function, which was related to improved cholinergic transmission efficiency (decreased acetylcholinesterase and increased acetylcholine), inhibition of the CaN/NFAT3/GATA4 pathway and suppression of the interaction of Orai1/STIM1.

Effect of grouped ST36 or RN12 on gastric motility and sensation

Objective: To investigate the effects of paired ST36 and RN12 acupuncture stimulation on gastric motility and the firing rate of responsible neurons in anesthetized rats. Methods: Using electrophysiological methods, we measured the effects of acupuncture at RN12, ST36, or RN12+ST36 on gastric motility as well as nerve discharges from the gastric sympathetic, vagal nerve, and wide dynamic range (WDR) neurons in the spinal dorsal horn T7-9 in anesthetized rats. Results: 1) Acupuncture at RN12 inhibited gastric motility (83.84±4.49)% and vagal nerve discharge (65.64±5.67)%, but promoted sympathetic nerve activity (243.70±40.67)%; acupuncture at ST36 induced opposing effects on gastric motility (111.31±2.01)% and vagal nerve discharge (166.98±15.92)%. Interestingly, acupuncture at RN12+ST36 together yielded effects similar to that of acupuncture at RN12 alone (93.59±2.05)%, (54.52±7.12)%. 2) WDR neuron discharges induced by gastric distension were inhibited by acupuncture at RN12 (194.56 ± 18.79)%. However, acupuncture at ST36 induced a more significant inhibitory effect. Conclusion: Acupuncture at RN12 inhibits gastric motility by activation of the sympathetic reflex at the spinal level; acupuncture at ST36 promotes gastric motility by activation of the parasympathetic reflex at the supraspinal level, and acupuncture at RN12+ST36 produces a similar decrease in gastric motility as RN12 stimulation alone. Both acupoints decrease the effect of noxious gastric distention on WDR neuron activity, but paired RN12+ST36 stimulation does not significantly affect WDR neuron discharge.

Brainstem sources of cardiac vagal tone and respiratory sinus arrhythmia.

Key points Cardiac vagal tone is a strong predictor of health, although its central origins are unknown.Respiratory‐linked fluctuations in cardiac vagal tone give rise to respiratory sinus arryhthmia (RSA), with maximum tone in the post‐inspiratory phase of respiration.In the present study, we investigated whether respiratory modulation of cardiac vagal tone is intrinsically linked to post‐inspiratory respiratory control using the unanaesthetized working heart‐brainstem preparation of the rat.Abolition of post‐inspiration, achieved by inhibition of the pontine Kolliker‐Fuse nucleus, removed post‐inspiratory peaks in efferent cardiac vagal activity and suppressed RSA, whereas substantial cardiac vagal tone persisted. After transection of the caudal pons, part of the remaining tone was removed by inhibition of nucleus of the solitary tract.We conclude that cardiac vagal tone depends upon at least 3 sites of the pontomedullary brainstem and that a significant proportion arises independently of RSA. Cardiac vagal tone is a strong predictor of health, although its central origins are unknown. The rat working heart‐brainstem preparation shows strong cardiac vagal tone and pronounced respiratory sinus arrhythmia. In this preparation, recordings from the cut left cardiac vagal branch showed efferent activity that peaked in post‐inspiration, ∼0.5 s before the cyclic minimum in heart rate (HR). We hypothesized that respiratory modulation of cardiac vagal tone and HR is intrinsically linked to the generation of post‐inspiration. Neurons in the pontine Kölliker‐Fuse nucleus (KF) were inhibited with bilateral microinjections of isoguvacine (50–70 nl, 10 mm) to remove the post‐inspiratory phase of respiration. This also abolished the post‐inspiratory peak of cardiac vagal discharge (and cyclical HR modulation), although a substantial level of activity remained. In separate preparations with intact cardiac vagal branches but sympathetically denervated by thoracic spinal pithing, cardiac chronotropic vagal tone was quantified by HR compared to its final level after systemic atropine (0.5 μm). Bilateral KF inhibition removed 88% of the cyclical fluctuation in HR but, on average, only 52% of the chronotropic vagal tone. Substantial chronotropic vagal tone also remained after transection of the brainstem through the caudal pons. Subsequent bilateral isoguvacine injections into the nucleus of the solitary tract further reduced vagal tone: remaining sources were untraced. We conclude that cardiac vagal tone depends on neurons in at least three sites of the pontomedullary brainstem, and much of it arises independently of respiratory sinus arrhythmia.

Brainstem-mediated sniffing and respiratory modulation during odor stimulation

The trigeminal and olfactory systems interact during sensory processing of odor. Here, we investigate odor-evoked modulations of brainstem respiratory networks in a decerebrated perfused brainstem preparation of rat with intact olfactory bulbs. Intranasal application of non-trigeminal odors (rose) did not evoke respiratory modulation in absence of cortico-limbic circuits. Conversely, trigeminal odors such as menthol or lavender evoked robust respiratory modulations via direct activation of preserved brainstem circuits. Trigeminal odors consistently triggered short phrenic nerve bursts (fictive sniff), and the strong trigeminal odor menthol also triggered a slowing of phrenic nerve frequency. Phrenic and vagal nerve recordings reveal that fictive sniffs transiently interrupted odor evoked tonic postinspiratory vagal discharge. This motor pattern is significantly different from normal (eupneic) respiratory activity. In conclusion, we show for the first time the direct involvement of brainstem circuits in primary odor processing to evoke protective sniffs and respiratory modulation in the complete absence of forebrain commands.

Cardiac reflexes in a warming world: thermal plasticity of barostatic control and autonomic tones in a temperate fish.

Thermal plasticity of cardiorespiratory function allows ectotherms like fish to cope with seasonal temperature changes and is critical for resilience to climate change. Yet, the chronic thermal effects on cardiovascular homeostatic reflexes in fish are little understood although this may have important implications for physiological performance and overall resilience to climate warming. We compared cardiac autonomic control and baroreflex regulation of heart rate in perch (Perca fluviatilis L.) from a reference area in the Baltic Sea at 18-19°C with conspecifics from the Biotest enclosure, a chronically heated ecosystem receiving warmed effluent water (24-25°C) from a nuclear power plant. Resting heart rate of Biotest fish displayed clear thermal compensation and was 58.3±2.3 beatsmin-1 compared with 52.4±2.6 beatsmin-1 in reference fish at their respective environmental temperatures (Q10=1.2). The thermally compensated heart rate of Biotest fish was a combined effect of elevated inhibitory cholinergic tone (105% in Biotest fish versus 70% in reference fish) and reduced intrinsic cardiac pacemaker rate. A barostatic response was evident in both groups, as pharmacologically induced increases and decreases in blood pressure resulted in atropine-sensitive bradycardia and tachycardia, respectively. Yet, the tachycardia in Biotest fish was significantly greater, presumably due to the larger scope for vagal release. Acclimation of Biotest fish to 18°C for 3 weeks abolished differences in intrinsic heart rate and autonomic tone, suggesting considerable short-term thermal plasticity of cardiovascular control in this species. The heightened hypotensive tachycardia in Biotest perch may represent an important mechanism of ectothermic vertebrates that safeguards tissue perfusion pressure when tissue oxygen demand is elevated by environmental warming.

Pharmacological Evidence that Histamine H3 Receptors Mediate Histamine-Induced Inhibition of the Vagal Bradycardic Out-flow in Pithed Rats.

In vivo stimulation of cardiac vagal neurons induces bradycardia by acetylcholine (ACh) release. As vagal release of ACh may be modulated by autoreceptors (muscarinic M2 ) and heteroreceptors (including serotonin 5-HT1 ), this study has analysed the pharmacological profile of the receptors involved in histamine-induced inhibition of the vagal bradycardic out-flow in pithed rats. For this purpose, 180 male Wistar rats were pithed, artificially ventilated and pre-treated (i.v.) with 1mg/kg atenolol, followed by i.v. administration of physiological saline (1ml/kg), histamine (10, 50, 100 and 200μg/kg) or the selective histamine H1 (2-pyridylethylamine), H2 (dimaprit), H3 (methimepip) and H4 (VUF 8430) receptor agonists (1, 10, 50 and 100μg/kg each). Under these conditions, electrical stimulation (3, 6 and 9Hz; 15±3V and 1ms) of the vagus nerve resulted in frequency-dependent bradycardic responses, which were (i) unchanged during the infusions of saline, 2-pyridylethylamine, dimaprit or VUF 8430; and (ii) dose-dependently inhibited by histamine or methimepip. Moreover, the inhibition of the bradycardia caused by 50μg/kg of either histamine or methimepip (which failed to inhibit the bradycardic responses to i.v. bolus injections of acetylcholine; 1-10μg/kg) was abolished by the H3 receptor antagonist JNJ10181457 (1mg/kg, i.v.). In conclusion, our results suggest that histamine-induced inhibition of the vagal bradycardic out-flow in pithed rats is mainly mediated by pre-junctional activation of histamine H3 receptors, as previously demonstrated for the vasopressor sympathetic out-flow and the vasodepressor sensory CGRPergic (calcitonin gene-related peptide) out-flow.

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.

Cardiac arrest after spinal anesthesia in a patient with neurally mediated syncope

We present the case of cardiac arrest in a patient with neurally mediated syncope (NMS). A 66-year-old male patient was scheduled to undergo right inguinal hernioplasty. He had a history of syncope, which occurred a few times a year in childhood and once a year recently. One minute after the second spinal injection, cardiac arrest (asystole) developed. Sinus rhythm was restored by cardiac massage and intravenous administration of atropine and ephedrine. The operation was cancelled. The patient was diagnosed as NMS by a cardiologist. Four months later, right inguinal hernioplasty was performed, uneventfully, under general anesthesia. High sympathetic blockade due to spinal anesthesia and transient withdrawal of sympathetic tone and increase in vagal discharge due to NMS could be the main causes of the cardiac arrest. If the patient has any possibility of NMS, anesthesiologists should consider the possibility of cardiac arrest after spinal anesthesia.

TRPA1 underlies a sensing mechanism for O2

Oxygen (O(2)) is a prerequisite for cellular respiration in aerobic organisms but also elicits toxicity. To understand how animals cope with the ambivalent physiological nature of O(2), it is critical to elucidate the molecular mechanisms responsible for O(2) sensing. Here our systematic evaluation of transient receptor potential (TRP) cation channels using reactive disulfides with different redox potentials reveals the capability of TRPA1 to sense O(2). O(2) sensing is based upon disparate processes: whereas prolyl hydroxylases (PHDs) exert O(2)-dependent inhibition on TRPA1 activity in normoxia, direct O(2) action overrides the inhibition via the prominent sensitivity of TRPA1 to cysteine-mediated oxidation in hyperoxia. Unexpectedly, TRPA1 is activated through relief from the same PHD-mediated inhibition in hypoxia. In mice, disruption of the Trpa1 gene abolishes hyperoxia- and hypoxia-induced cationic currents in vagal and sensory neurons and thereby impedes enhancement of in vivo vagal discharges induced by hyperoxia and hypoxia. The results suggest a new O(2)-sensing mechanism mediated by TRPA1.

Cardiac Vagal Efferent Discharge Does Not Decrease During Spontaneous Fictive Motor Activity In Decerebrate Cats

Cardiac Vagal Efferent Discharge Does Not Decrease During Spontaneous Fictive Motor Activity In Decerebrate Cats

Arrhythmogenic Foci and the Mechanisms of Atrial Fibrillation

In this issue of the Circulation: Arrhythmia and Electrophysiology , Kurotobi et al1 determined the number of arrhythmogenic foci in atria provocable with isoproterenol infusion in patients with paroxysmal, persistent, and permanent atrial fibrillation (AF). The results show that persistent AF has more foci than paroxysmal AF. However, when AF persists for >12 months, the number of foci were reduced. The authors suggest that the increased number of foci probably is involved in the development of persistent AF. However, because this association is not observed for AF that persists for >12 months, the importance of these foci in AF maintenance remains unclear. Article see p 39 In ambulatory canine models, simultaneous sympathovagal discharges (rather than isolated sympathetic activation) are typical triggers of paroxysmal atrial tachycardia (AT) and AF.2,3⇓ These observations are explained by the late phase-3 early afterdepolarization (EAD), which depends on the coexistence of increased amplitude and duration of intracellular calcium (Cai) transient and the shortened action potential duration (APD).4,5⇓ Vagal stimulation shortens APD and therefore is needed to promote the late phase-3 EAD. In the Kurotobi study, however, arrhythmogenic foci were induced by isoproterenol alone, without the need of vagal stimulation or the use of parasympathomimetic agents. These results are different from that obtained in canine studies. The first possible explanation is that the pulmonary veins (PVs) naturally have shorter APDs with elevated (less negative) membrane potentials.6,7⇓ Rapid activation may further shorten the APD in the PVs.8 These changes are independent of the vagal tone. Jais et al9 reported the effective refractory periods of the PVs were shorter …

Cardiovascular effects induced by Cymbopogon winterianus essential oil in rats: involvement of calcium channels and vagal pathway

This study has investigated the cardiovascular effects of the Cymbopogon winterianus essential oil (EOCW) in rats. C. winterianus is a plant used in folk medicine for the treatment of hypertension. For the measurement of haemodynamic and ECG parameters, male Wistar rats under anaesthesia were cannulated in the abdominal aorta and lower vena cava and electrodes were subcutaneously implanted in their paws. For an in-vitro approach, the rats were killed and the superior mesenteric artery was removed and cut into rings (1-2 mm). These rings were then mounted in organ baths containing Tyrode's solution at 37 degrees C and gassed with carbogen. In rats, EOCW (1-20 mg/kg, i.v.) induced dose-dependent hypotension and tachycardia. These effects were not affected by L-NAME or indometacin, but were partially reduced after atropine administration. EOCW (20 mg/kg only) also induced bradycardia-associated sinoatrial blockade, junctional rhythm, and first-degree atrioventricular block, which was abolished after atropine administration or vagotomy. In arterial rings, EOCW (0.1-3000 microg/ml) induced relaxation of phenylephrine tonus that was not affected by removal of the endothelium. These relaxations were similar to those observed in rings without endothelium precontracted with KCl 80 mm. EOCW was able to antagonize the CaCl(2) (30-300 mum) induced contractions in depolarizing solution (KCl 60 mm). These results demonstrated that EOCW induced hypotension and vasorelaxation. These effects appeared to be mainly mediated by Ca(+2)-channel blocking. Furthermore, the higher dose of EOCW induced transient bradycardia and arrhythmias due to a cardiac muscarinic activation secondary to a vagal discharge.

Effect of Electroacupuncture on St. 36 (Zusanli) and LI. 10 (Shousanli) Acupuncture Points on Heart Rate Variability

Electrical stimulation of St. 36 (Zusanli) has been shown to enhance the regularity of gastric myoelectrical activity in healthy subjects. However, the underlying mechanism by which acupuncture alters gastric myoelectrical activity is still not clear. To elucidate the possible role of the autonomic nervous system in mediating the effect of acupuncture, we monitored heart rate variability (HRV), a widely used index of vagal discharge at the sinoatrial node of the heart before, during and after electroacupuncture. In this study, we applied two different frequencies (2 Hz and 100 Hz) of electrical stimulation at St. 36 (Zusanli) and LI. 10 (Shousanli) in 15 healthy volunteers. Low frequency (LF, sympathetic activity), high frequency (HF, vagal activity) and LF/HF ratio (sympathovagal balance) were analyzed and compared at the two different frequencies. The results showed an increase in the LF/HF ratio (indicating greater sympathetic activity) during the post-acupuncture period using 2 Hz of electrical stimulation at St. 36 (Zusanli). However, the overall change was not statistically significant. In addition, the power of LF and HF did not change significantly with electroacupuncture at St. 36 (Zusanli) and LI. 10 (Shousanli). In conclusion, applying 2 Hz or 100 Hz electroacupuncture at St. 36 (Zusanli) or LI. 10 (Shousanli) did not affect cardiovagal activity in normal volunteers. This phenomenon might be due to a difference in presentation in the autonomic nervous system between cardiac and abdominal vagal activity.