Cold Face Test Research Articles

Cardiovascular reflex tests detect autonomic dysfunction in symptomatic and pre-symptomatic subjects with hereditary transthyretin amyloidosis.

Autonomic dysfunction is a distinctive but undervalued feature of hereditary transthyretin amyloidosis (ATTRv). It may predate the onset of polyneuropathy and cardiomyopathy, thereby providing crucial prognostic and therapeutic information. The objective of this study was to assess autonomic function by means of the standardized cardiovascular autonomic reflex tests (CRTs) in a cohort of subjects with genetically proven ATTRv from non-endemic areas who were in the symptomatic and pre-symptomatic stages. All subjects enrolled in this cross-sectional study had genetically proven ATTRv. They underwent the head-up tilt test, Valsalva manoeuvre, deep breathing test, cold face test and handgrip test while under continuous blood pressure and heart rate monitoring. Based on the results of the nerve conduction study, the subjects were divided into two groups: those with polyneuropathy (ATTRv-wPN) and those without polyneuropathy (ATTRv-woPN). Age- and sex-matched healthy controls (HC) were used for comparison. Thirty-seven ATTRv subjects (19 with ATTRv-wPN, 18 with ATTRv-woPN) and 41 HC performed the CRTs. Of these 37 subjects with ATTRv, four (11%) presented neurogenic orthostatic hypotension the during head-up tilt test. Based on the results of the CRTs, autonomic dysfunction characterized by either sympathetic or parasympathetic impairment was detected in 37% and 63% of ATTRv-wPN subjects, respectively. Subjects with ATTRv-woPN presented a significant impairment of autonomic responses to the Valsalva manoeuvre compared to the HC (overshoot p = 0.004; Valsalva ratio p = 0.001). Autonomic dysfunctions are frequent in subjectswith ATTRv when investigated by means of standardized CRTs, and are also relevant in the pre-symptomatic stage. Cardiovagal functions are the primary functions affected, among others. This may be crucial in defining the proper diagnostic workout for early diagnosis and improving the likelihood of providing the patient with prompt administration of disease-modifying treatments.

Vagus activation by Cold Face Test reduces acute psychosocial stress responses

Chronic stress is linked to dysregulations of the two major stress pathways—the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis, which could for example result from maladaptive responses to repeated acute stress. Improving recovery from acute stress could therefore help to prevent this dysregulation. One possibility of physiologically interfering with an acute stress reaction might be provided by applying a cold stimulus to the face (Cold Face Test, CFT) which activates the parasympathetic nervous system (PNS), leading to immediate heart rate decreases. Therefore, we investigated the use of the CFT protocol as an intervention to reduce acute stress responses. Twenty-eight healthy participants were exposed to acute psychosocial stress via the Montreal Imaging Stress Task (MIST) in a randomized between-subjects design while heart rate (HR), heart rate variability (HRV), and salivary cortisol were assessed. While both groups were equally stressed during the procedure, participants with CFT intervention showed better recovery, indicated by significant (p<0.05) differences in HR(V). We additionally found a significantly (p<0.05) lower cortisol response to the MIST and less overall cortisol secretion in the CFT condition. Both findings indicate that the CFT can successfully stimulate the PNS and inhibit the HPA axis. To the best of our knowledge, our experiment is the first to successfully use the CFT as a simple and easy-to-apply method to modify biological responses to acute stress.

Respiratory and heart rate dynamics during peripheral chemoreceptor deactivation compared to targeted sympathetic and sympathetic/parasympathetic (co-)activation.

The importance of peripheral chemoreceptors for cardiorespiratory neural control is known for decades. Pure oxygen inhalation deactivates chemoreceptors and increases parasympathetic outflow. However, the relationship between autonomic nervous system (ANS) activation and resulting respiratory as well as heart rate (HR) dynamics is still not fully understood. In young adults the impact of (1) 100% pure oxygen inhalation (hyperoxic cardiac chemoreflex sensitivity (CHRS) testing), (2) the cold face test (CFT) and (3) the cold pressor test (CPT) on heart rate variability (HRV), hemodynamics and respiratory rate was investigated in randomized order. Baseline ANS outflow was determined assessing respiratory sinus arrhythmia via deep breathing, baroreflex sensitivity and HRV. Baseline ANS outflow was normal in all participants (23±1years, 7 females, 3 males). Hyperoxic CHRS testing decreased HR (after 60±3 vs before 63±3min-1, p=0.004), while increasing total peripheral resistance (1053±87 vs 988±76dyne*s+m2/cm5, p=0.02) and mean arterial blood pressure (93±4 vs 91±4mmHg, p=0.02). HRV indicated increased parasympathetic outflow after hyperoxic CHRS testing accompanied by a decrease in respiratory rate (15±1vs 19±1min-1, p=0.001). In contrast, neither CFT nor CPT altered the respiratory rate (18±1 vs 18±2min-1, p=0.38 and 18±1 vs 18±1min-1, p=0.84, respectively). Changes in HR characteristics during deactivation of peripheral chemoreceptors but not during the CFT and CPT are related with a decrease in respiratory rate. This highlights the need of respiratory rate assessment when evaluating adaptations of cardiorespiratory chemoreceptor control.

Cardiovascular reactivity to and recovery from cold face test

The purpose of this study was to investigate reactivity and recovery to primarily parasympathetic stimulation by cold face test.Sixty five students with a mean age of 20.61±0.13 years take part in the study (86% women, 14% men). They were studied in the morning hours in a quiet room at a comfortable temperature. Time domain (SDNN, RMSSD, pNN50), frequency domain (TP, HF, VLF, LF and LF/HF ratio) and nonlinear (SD1, SD2, ApEn, SampEn, D2, DFA1, DFA2) parameters of HRV were obtained from all participants for 5 minutes before, 5 minutes during and 5 minutes after cold face test (0–1 °C cold compresses) in a supine position. Statistical analysis was performed using Mann‐Whitney test.Heart rate during cold face test was significantly lower than that during rest period (74.03±1.26 vs 76.74±1.21 beat/min, p=0.006). After cold face test cessation heart rate displayed significant decrease compared to cold face test period (71.96±1.17 vs 74.03±1.26 beat/min, p=0.001). Time domain parameters were found to be higher during cold face test than that during rest (SDNN: 52.6±2.85 vs 43.61±2.23 ms, p=0.006; RMSSD: 59.87±4.08 vs 44.99±2.93 ms, p=0.001 and pNN50: 30.49±2.38 vs 22.07±2.13 %, p=0.003). During recovery period time domain parameters remain to be higher, than that during rest: SDNN – 47.97±2.29 ms, RMSSD – 52.16±3.35 ms, pNN50 – 27.24±2.38%.There was no differences during rest period, cold face test and recovery period in TP (2097.89±249.98 vs 2517.24±301.8 vs 2176.12±204 ms2, p=0.744), VLF (83.59±9.99 vs 92.44±12.21 vs 88.33±7.85 ms2, p=0.359), LF (932.86±107.70 vs 1024.98±132.06 ms2, vs 928.54±83.35, p=0.896). High frequency parameter was significantly higher during cold face test than that during rest (1395.36±184.39 vs 1078.11±143.13 ms2, p=0.013). After cold test HF parameter was 1156.11±129.74 ms2(p&gt;0.05).Nonlinear measures were significantly higher during cold face test than that during rest (SD1: 42.39±2.89 vs 31.83±2.07 ms, p=0.001; SD2: 60.52±3.04 vs 52.45±2.50 ms, p=0.025). During recovery period nonlinear parameters remain to be higher, than that during rest: SD1 – 36.92±2.29 ms, SD2 – 56.34±2.44 ms, pNN50 – 27.24±2.38%. ApEn and DFA1 were significantly lower during cold face test than that during rest (respectively, 1.15±0.01 vs 1.40±0.01 and 0.87±0.03 vs 1.01±0.02, p&lt;0.001). During recovery period ApEn was 1.37±0.01 and DFA1 was 0.96±0.03.The other HRV parameters including D2, LF/HF ratio, pLF, pHF, SampEn, DFA2 were not significantly different.These results suggest that cold face test has been associated with increased vagal cardiac control and decrease entropy and DFA1.

Neurogenic orthostatic hypotension in early stage Parkinson's disease: New insights from the first 105 patients of the BoProPark study

ObjectivesThe prevalence of neurogenic orthostatic hypotension (NOH, due to cardiovascular autonomic failure) at early stage of Parkinson's disease (PD) is unknown. The aims of this study are to prospectively evaluate in a cohort of PD patients recruited within 3 years from motor onset (1) cardiovascular autonomic functions by means of cardiovascular reflex tests (CRTs) and the occurrence of NOH; (2) the frequency of orthostatic symptoms with a validated questionnaire. MethodsWe included the first 105 PD patients of the prospective “BoProPark” study. Each patient underwent CRTs (head up tilt test; Valsalva manoeuvre; deep breathing; cold face test and handgrip test) under continuous blood pressure monitoring according to standardized procedures and SCOPA-Aut questionnaire at baseline (T0) and after 16 months (T1). A group of 50 age- and sex-matched controls was used for comparison. ResultsAt T0 (mean age 61 ± 9 years, disease duration 19 ± 9 months) NOH was detected in 4/105 (3.8%) patients, whereas at T1 in 8/105 (7.6%). CRTs responses assessing sympathetic function were impaired at T0 in PD patients compared to controls and progressively worsened at T1. Only 1 patient at T0 and 3 at T1 with NOH reported orthostatic symptoms with low frequency, while the majority of patients reporting these symptoms did not have OH at testing. ConclusionsOur prospective study shows that NOH is not common at early PD stage. Asymptomatic mild sympathetic impairment was observed at first evaluation and progressed with disease evolution. Secondary OH may account for the higher prevalence of OH in PD reported so far.

Decreased Autonomic Reactivity and Psychiatric Comorbidities in Neurological Patients With Medically Unexplained Sensory Symptoms: A Case-Control Study

Up to 48% of patients with medically unexplained symptoms seen in neurological practice suffer from sensory symptoms, which could be of functional nature or secondary to psychiatric disorders. These patients show high medical care utilization causing elevated healthcare costs. Despite the high prevalence, little is known about clinical characteristics and pathophysiological mechanisms. For functional disorders such as irritable bowel syndrome, a reduction of heart rate variability (HRV) has been shown, suggesting a dysfunction of the autonomic nervous system (ANS). The aim of this study was to investigate psychological data and functional changes of the ANS in patients with medically unexplained sensory symptoms (MUSS). In this exploratory pilot study, 16 patients (11 females, 31.6 ± 11.9 years) with MUSS, who were recruited at a single tertiary neurological center, underwent a structured clinical interview (SCID) to evaluate psychiatric comorbidities. Patients and age- and sex-matched healthy volunteers filled in questionnaires, and individual sensory thresholds (perception, pain) were detected by quantitative sensory testing (QST). HRV was assessed at baseline and under three different experimental conditions (tonic pain stimulus, placebo application, cold-face test). All tests were repeated after 6–8 weeks. SCID interviews revealed clinical or subclinical diagnoses of psychiatric comorbidities for 12 patients. Questionnaires assessing somatization, depression, anxiety, and perceived stress significantly discriminated between patients with MUSS and healthy controls. While there was no difference in QST, reduced ANS reactivity was found in patients during experimental conditions, particularly with regard to vagally mediated HRV. Our pilot study of neurological patients with MUSS reveals a high prevalence of psychiatric comorbidities and provides evidence for altered ANS function. Our data thus give insight in possible underlying mechanisms for these symptoms and may open the door for a better diagnostic and therapeutic approach for these patients in the future.

Altered Cardiovascular Reactivity to and Recovery from Cold Face Test-Induced Parasympathetic Stimulation in Essential Hypertension.

Essential hypertension is associated with increased sympathetic and diminished parasympathetic activity as well as impaired reactivity to sympathetic stimulation. However, reactivity and recovery from parasympathetic stimulation in hypertension are unknown. We investigated reactivity and recovery to primarily parasympathetic stimulation by Cold Face Test (CFT) in essential hypertension. Moreover, we tested whether chronic stress modulates CFT-reactivity dependent on hypertension status. The CFT was conducted by applying a cold face-mask for 2 min in 24 unmedicated, otherwise healthy hypertensive men and in 24 normotensive controls. Systolic and diastolic blood pressure (BP) and heart rate (HR) were measured repeatedly. Chronic stress was assessed with the Trier-Inventory-for-Chronic-Stress-Screening-Scale. Hypertensives did not exhibit diastolic BP decreases after CFT-cessation (p = 0.59) as did normotensives (p = 0.002) and failed to show HR decreases in immediate response to CFT (p = 0.62) when compared to normotensives (p < 0.001). Systolic BP reactivity and recovery patterns did not differ between hypertensives and normotensives (p = 0.44). Chronic stress moderated HR (p = 0.045) but not BP CFT-reactivity (p′s > 0.64) with chronically stressed normotensives showing similar HR reactivity as hypertensives. Our findings indicate impaired diastolic BP and HR reactivity to and recovery from CFT in hypertensives and a moderating effect of chronic stress on HR reactivity potentially reflecting reduced relaxation ability of the cardiovascular system.

Self-Reported Emotion Regulation Is Associated With Response to Test of Cardiac Vagal Function

Abstract. Parasympathetic function and emotional self-regulation (ESR) share neuroanatomic structures. Based on Porges’ Polyvagal Theory and the Neurovisceral Integration Model (NIM), we compared vagally mediated heart-rate variability (vmHRV) with psychometrically assessed ESR. We hypothesized that vmHRV and ESR would be associated during rest, a vagal function test, and recovery from that test. A significant association would justify the psychometric measuring of parasympathetic health, which is less burdensome than its psychophysiological assessment. Two hundred thirteen healthy males (aged: 18–26 years, M = 20.29 years) took part in the present study. They completed the Emotion Regulation Questionnaire (ERQ) and underwent the Cold Face Test (CFT) for 4 min wearing ambulatory electrocardiograms. A High frequency (HF) band was used as a measure of vmHRV before, during, and after the CFT. Associations between the HF band and ESR were analyzed with partial rank correlations. There was no significant association between ERQ scores and the response to the CFT itself. But there was an almost significant association between the ERQ scale Cognitive Appraisal and baseline vmHRV, and a significant association between Cognitive Appraisal and cardiac recovery from the CFT, that is, participants with higher scores on that ESR scale revealed a tendency to exhibit greater vmHRV during baseline and they exhibited greater vagal withdrawal during recovery from the CFT. Cognitive appraisal as a psychometrically assessed emotion regulatory process was reflected in a more flexible parasympathetic activity (i.e., better cardiac vagal health) during recovery from an exclusively physiological stressor. This lends convergent validity to self-reported emotion regulation, and justification for its use as a measure of ESR as a trait, offering further support for the Polyvagal Theory and NIM.

Effects of the cold face test on heart rate variability in students

The purpose of this study was to determine the effects of the cold pressor test on heart rate variability in students. Sixty five students with a mean age of 20.61±0.13 years take part in the study (86% women, 14% men). They were studied in the morning hours in a quiet room at a comfortable temperature. Time domain (SDNN, RMSSD, pNN50), frequency domain (TP, HF, VLF, LF and LF/HF ratio) and nonlinear (SD1, SD2, ApEn, SampEn, D2, DFA1, DFA2) parameters of HRV were obtained from all participants for 5 minutes before and 5 minutes during cold face test (0–1 °C cold compresses) in a supine position. Statistical analysis was performed using Mann-Whitney test. Heart rate during cold face test was significantly lower than that during rest period (74.03±1.26 vs 76.74±1.21 beat/min, p=0.006). Time domain parameters were found to be higher during cold face test than that during rest (SDNN: 52.6±2.85 vs 43,61±2,23 ms, p=0.006; RMSSD: 59.87±4.08 vs 44.99±2.93 ms, p=0.001 and pNN50: 30.49±2.38 vs 22.07±2.13 %, p=0.003). There was no differences during cold face test period and rest period in TP (2517.24±301.8 vs 2097.89±249.98 ms2, p=0.456; VLF: 92.44±12.21 vs 83.59±9.99 ms2, p=0.452; LF: 1024.98±132.06 vs 932.86±107.70 ms2, p=0.896. High frequency parameter was significantly higher during cold face test than that during rest (1395.36±184.39 vs 1078.11±143.13 ms2, p=0.013). Nonlinear measures were significantly higher during cold face test than that during rest (SD1: 42.39±2.89 vs 31.83±2.07 ms, p=0.001; SD2: 60.52±3.04 vs 52.45±2.50 ms, p=0.025). ApEn and D1 were significantly lower during cold face test than that during rest (respectively, 1.15±0.01 vs 1.40±0.01 and 0.87±0.03 vs 1.01±0.02, p<0.001). The other HRV parameters including D2, LF/HF ratio, pLF, pHF, SampEn, DFA2 were not significantly different. These results suggest that cold face test has been associated with increased vagal cardiac control and decrease entropy and D1.

Decreased Autonomic Reactivity and Psychiatric Comorbidities in Neurological Patients with Medically Unexplained Sensory Symptoms: A Case-Control Study

Background: Up to 48% of patients with medically unexplained symptoms seen in neurological practice suffer from sensory symptoms, which could be of functional nature or secondary to mental disorders. These patients show high medical care utilization causing elevated health care costs. Despite the high prevalence, little is known about clinical characteristics and pathophysiological mechanisms. For functional disorders such as irritable bowel syndrome a reduction of heart rate variability (HRV) has been shown, suggesting a dysfunction of the autonomic nervous system (ANS). The aim of this study was to investigate psychological data and functional changes of the ANS in patients with medically unexplained sensory symptoms (MUSS). Methods: In this exploratory pilot study, 16 patients (11 females, 31·6 ± 11·9 years) with MUSS, who were recruited at a single tertiary neurological centre, underwent a structured clinical interview (SCID) to evaluate psychiatric comorbidities. Patients and age- and sex-matched healthy volunteers filled in questionnaires, and individual sensory thresholds (perception, pain) were detected by quantitative sensory testing (QST). HRV was assessed at baseline and under three different experimental conditions (tonic pain stimulus, placebo application, cold face test). All tests were repeated after 6-8 weeks. Findings: SCID interviews revealed clinical or subclinical diagnoses of psychiatric comorbidities for 12 patients. Questionnaires assessing somatization, depression, anxiety, and perceived stress significantly discriminated between patients and controls. While there was no difference in QST, reduced ANS reactivity was found in patients during experimental conditions, particularly with regard to vagally-mediated HRV. Interpretation: Our pilot study of neurological patients with MUSS reveals a high prevalence of psychiatric comorbidities and provides evidence for altered ANS function. Our data thus give insight in possible underlying mechanisms for these symptoms and may open the door for a better diagnostic and therapeutic approach for these patients in the future. Funding: No external funding was obtained for this study. Declaration of Interest: All authors declare to have no conflicts of interest. Ethical Approval: Approval for the study was obtained by the Ethics Committee of the medical faculty of Tubingen University (Project No. 765/2015BO2).

Cardiovascular Autonomic Dysfunction in Spinal Cord Injury: Epidemiology, Diagnosis, and Management.

Spinal cord injury (SCI) disrupts autonomic circuits and impairs synchronistic functioning of the autonomic nervous system, leading to inadequate cardiovascular regulation. Individuals with SCI, particularly at or above the sixth thoracic vertebral level (T6), often have impaired regulation of sympathetic vasoconstriction of the peripheral vasculature and the splanchnic circulation, and diminished control of heart rate and cardiac output. In addition, impaired descending sympathetic control results in changes in circulating levels of plasma catecholamines, which can have a profound effect on cardiovascular function. Although individuals with lesions below T6 often have normal resting blood pressures, there is evidence of increases in resting heart rate and inadequate cardiovascular response to autonomic provocations such as the head-up tilt and cold face tests. This manuscript reviews the prevalence of cardiovascular disorders given the level, duration and severity of SCI, the clinical presentation, diagnostic workup, short- and long-term consequences, and empirical evidence supporting management strategies to treat cardiovascular dysfunction following a SCI.

Autonomic symptoms, cardiovascular and sudomotor evaluation in de novo type 1 narcolepsy.

To evaluate cardiovascular and sudomotor function during wakefulness and to assess autonomic symptoms in de novo patients with type 1 narcolepsy compared to healthy controls. De novo patients with type 1 narcolepsy (NT1) and healthy controls underwent cardiovascular function tests including head-up tilt test, Valsalva maneuver, deep breathing, hand grip, and cold face, and sudomotor function was assessed through Sudoscan. Autonomic symptoms were investigated using the Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction (SCOPA-AUT) questionnaire. Twelve de novo patients with NT1 and 14 healthy controls were included. In supine rest condition and at 3min and 10min head-up tilt test, the systolic blood pressure values were significantly higher in the NT1 group than in controls (p < 0.05). A lower Valsalva ratio (p < 0.01), significantly smaller inspiratory-expiratory difference in deep breathing (p < 0.05), and lower delta heart rate in the cold face test (p < 0.01) were also observed in the NT1 group. The mean hand electrochemical skin conductance values were significantly lower (p < 0.05) and the mean SCOPA-AUT total scores were significantly higher in patients with NT1 than in healthy subjects (p < 0.001), with greater involvement of cardiovascular and thermoregulatory items. De novo patients with NT1 exhibit blunted parasympathetic activity during wakefulness, mild sudomotor dysfunction, and a large variety of autonomic symptoms.

Non-invasive Recording of Parasympathetic Nervous System Activity on Auricular Vagal Nerve Branch.

The function of the autonomic nervous system (ANS) influences most of the physiological mechanisms. The popular non-invasive method to estimate the activities of the autonomic nervous system (ANS) is the heart rate variability (HRV). However, the HRV cannot provide real-time information of the ANS function. The skin sympathetic nerve activity (SKNA) is a novel method to evaluate sympathetic nerve system (SNS) activity. The SKNA technique has shown promise in clinical applications but is limited to evaluating SNS activities. To date, a direct non-invasive method for measuring the parasympathetic nerve system (PNS) function is urgently needed. According to anatomy, the auricular branch of the vagus nerve (aVN) is near the concha surface. In this study, we hypothesize that we can measure the aVN activity (aVNA) with the same technique developed for SKNA recording. Flexible auricular electrodes were developed for continuous long-term recording of aVN activity. The SKNA and aVNA were simultaneously recorded during the experiment. The cold face test and cold pressor test were performed to physiologically activate ANS. The SKNA and aVNA can be obtained simultaneously, and they are correlated with the heart rate change during the physiological challenge. The aVNA has a high potential to be developed into a novel method to measure the PNS activity.

Treatment with Dimethyl Fumarate Enhances Cholinergic Transmission in Multiple Sclerosis.

Dimethyl fumarate (DMF) exerts anti-inflammatory effects in multiple sclerosis by activating the Nrf2 antioxidant pathway, which is also stimulated by acetylcholine via alpha-7 nicotinic acetylcholine receptors. In animal models, Nrf2 potentiates cholinergic synaptic plasticity. The aim of this study was to test whether treatment with DMF modulates cholinergic pathways in relapsing-remitting multiple sclerosis (RRMS). Patients starting DMF (20) or IFN-β 1a (20) and healthy subjects (20) were enrolled. Short-latency afferent inhibition (SAI), which is a transcranial stimulation measure of central cholinergic transmission, was recorded in patients and controls at baseline and, in patients only, after 6months of treatment. Patients treated with DMF also underwent autonomic function testing to further explore peripheral and central cholinergic tone. At baseline, SAI was similar in patients and in controls (p = 0.983). Treatment with DMF significantly increased SAI (p = 0.01), while IFNβ had no effect (p = 0.80). In the cold face test, DMF treatment also increased reflex bradycardia (p = 0.013), and reduced diastolic blood pressure variation (p = 0.010), further indicating its ability to stimulate cholinergic transmission. Treatment of MS patients with DMF results in increased cholinergic stimulation, with possible implications for neuroinflammation and neuroprotection.

Respiratory sinus arrhythmia is reduced after pulmonary vein isolation in patients with paroxysmal atrial fibrillation.

IntroductionRespiratory sinus arrhythmia (RSA) describes heart rate (HR) changes in synchrony with respiration. It is relevant for exercise capacity and mechanistically linked with the cardiac autonomic nervous system. After pulmonary vein isolation (PVI), the current therapy of choice for patients with paroxysmal atrial fibrillation (AF), the cardiac vagal tone is often diminished. We hypothesized that RSA is modulated by PVI in patients with paroxysmal AF.Material and methodsRespiratory sinus arrhythmia, measured by using a deep breathing test and heart rate variability parameters, was studied in 10 patients (64 ±3 years) with paroxysmal AF presenting in stable sinus rhythm for their first catheter-based PVI. Additionally, heart rate dynamics before and after PVI were studied during sympathetic/parasympathetic coactivation by using a cold-face test. All tests were performed within 24 h before and 48 h after PVI.ResultsAfter PVI RSA (E/I difference: 7.9 ±1.0 vs. 3.5 ±0.6 bpm, p = 0.006; E/I ratio: 1.14 ±0.02 vs. 1.05 ±0.01, p = 0.003), heart rate variability (SDNN: 31 ±3 vs. 14 ±3 ms, p = 0.006; RMSSD: 17 ±2 vs. 8 ±2 ms, p = 0.002) and the HR response to sympathetic/parasympathetic coactivation (10.2 ±0.7% vs. 5.7 ±1.1%, p = 0.014) were diminished. The PVI-related changes in RSA correlated with the heart rate change during sympathetic/parasympathetic coactivation before vs. after PVI (E/I difference: r = 0.849, p = 0.002; E/I ratio: r = 0.786, p = 0.007). One patient with vagal driven arrhythmia experienced AF recurrence during follow-up (mean: 6.5 ±0.6 months).ConclusionsRespiratory sinus arrhythmia is reduced after PVI in patients with paroxysmal AF. Our findings suggest that this is related to a decrease in cardiac vagal tone. Whether and how this affects the clinical outcome including exercise capacity need to be determined.

Cardiac parasympathetic activity and ventricular diastolic interactions in individuals with spinal cord injury.

Cohort cross-sectional study. To investigate the relationship between cardiac vagal activity and left ventricular filling at rest and during vagal stimulation, via the cold face test (CFT), in individuals with spinal cord injury (SCI). University-based laboratory at Brock University, St. Catharines, ON, Canada. A total of 12 able-bodied (age: 40 ± 8.5 years) and 13 SCI individuals (age: 41 ± 8.5 years; C4-T6; AIS: A-D) were recruited. Cardiac parasympathetic activity was assessed via heart rate variability (HRV) while LV filling was assessed by conventional echocardiography. All indices of HRV and diastolic function were obtained at rest and during cardiac vagal stimulation via the CFT. At baseline, the able-bodied group demonstrated strong positive correlations between HRV and early diastolic filling; however, such correlations were absent in the SCI group. The CFT resulted in elevated HRV with concomitant bradycardia in the able-bodied group, while the SCI group experienced no change in HRV or heart rate during the CFT. Able-bodied individuals showed a positive correlation between the change in HRV and the change in LV diastole during the CFT, which was attributed to increased cardiac vagal tone and not the change in heart rate, however, no relationships were observed in the SCI group. In able-bodied individuals, cardiac parasympathetic activity is associated with LV filling at rest and during elevated cardiac vagal tone. After SCI, there is a discord between vagal and LV diastolic activity, where changes in autonomic function do not influence LV filling, suggesting a disconnect between parasympathetic and cardiac function.

A call to reevaluate cardiac autonomic assessment after spinal cord injury

This "Perspectives" article puts forward the notion that measuring heart rate variability, or other forms of cardiac autonomic regulation, after spinal cord injury must be performed during a test of autonomic stress. Resting values of heart rate variability are often similar to those obtained from able-bodied individuals, which may therefore be falsely interpreted as normal or healthy autonomic regulation. However, evidence shows that despite normal resting values, cardiac autonomic control is impaired when individual with spinal cord injury are subjected to a cold face test, head-up tilt, or recovery from exercise. Accordingly, examination of cardiac autonomic function must be performed during an autonomic challenge, as resting measures do not accurately reflect the state of cardiovascular regulation after spinal cord injury and can provide false information.

Cardiovascular Effects of Stress During Acutely Increased Free Fatty Acids in a Randomized, Double-Blind, Cross-Over Study in Humans.

Increased free fatty acids stimulate sympathetic nervous system activity, impair endothelium-dependent vasodilation, and increase regional blood flow. The aim of this study was to assess if fatty acids acutely elevated by infusion of intralipid/heparin affect cardiovascular reactivity employing two stressors eliciting either a cardiac (Stroop test) or vascular (Cold Face test) dominated pressor response. Two stress tasks were performed in 20 healthy subjects (10 women, 10 men) before and during a 180-min intralipid/heparin or saline infusion as placebo on alternate trial days in a randomized crossover study design. Blood pressure, heart rate, cardiac index, and total peripheral resistance index were measured. At baseline, the Stroop test did not affect hemodynamic parameters, and the Cold Face test had an impact on hemodynamic parameters except for heart rate. Plasma fatty acids concentrations increased to 810% (t=11.0, p<0.001) of baseline and C-peptide increased by 17% (t=4.66, p<0.001) during intralipid/heparin infusion. This was paralleled by increased cardiac index (F=9.98; p<0.005 vs. saline) and reduced total peripheral resistance index (F=4.46; p<0.05 vs saline). There was no effect of intralipid/heparin or saline infusion on Stroop test or Cold Face test reactivity of hemodynamic parameters. An acute increase in free fatty acids does not affect the magnitude or pattern of stress response in healthy volunteers, but primarily alter the underlying cardiovascular tone by decreasing total peripheral resistance index and increasing cardiac index to maintain a constant blood pressure.

Sympathetic and Parasympathetic Coactivation Induces Perturbed Heart Rate Dynamics in Patients with Paroxysmal Atrial Fibrillation.

BackgroundRecent evidence indicates that sympathetic/parasympathetic coactivation (CoA) is causally linked to changes in heart rate (HR) dynamics. Whether this is relevant for patients with atrial fibrillation (AF) is unknown.Material/MethodsIn patients with paroxysmal AF (n=26) and age-matched controls, (n=10) we investigated basal autonomic outflow and HR dynamics during separate sympathetic (cold hand immersion) and parasympathetic activation (O2-inhalation), as well as during CoA (cold face test). In an additional cohort (n=7), HR response was assessed before and after catheter-based pulmonary vein isolation (PVI). Ultra-high-density endocardial mapping was performed in patients (n=6) before and after CoA.ResultsSympathetic activation increased (control: 74±3 vs. 77±3 bpm, p=0.0098; AF: 60±2 vs. 64±2 bpm, p=0.0076) and parasympathetic activation decreased HR (control: 71±3 vs. 69±3 bpm, p=0.0547; AF: 60±1 vs. 58±2 bpm, p<0.0009), while CoA induced a paradoxical HR increase in patients with AF (control: 73±3 vs. 71±3 bpm, p=0.084; AF: 59±2 vs. 61±2 bpm, p=0.0006), which was abolished after PVI. Non-linear parameters of HR variability (SD1) were impaired during coactivation in patients with AF (control: 61±7 vs. 69±6 ms, p=0.042, AF: 44±32 vs. 32±5 ms, p=0.3929). CoA was associated with a shift of the earliest activation site (18±4 mm) of the sinoatrial nodal region, as documented by ultra-high-density mapping (3442±343 points per map).ConclusionsCoA perturbs HR dynamics and shifts the site of earliest endocardial activation in patients with paroxysmal AF. This effect is abolished by PVI, supporting the value of emerging methods targeting the intrinsic cardiac autonomic nervous system to treat AF. CoA might be a valuable tool to assess cardiac autonomic function in a clinical setting.

31. Does continuous positive airway pressure treatment affect autonomic nervous system in patients with severe obstructive sleep apnea?

To evaluate whether Continuous Positive Airway Pressure treatment (CPAP) affect autonomic nervous system (ANS) in patients with severe obstructive sleep apnea (OSAS). We compared de novo OSAS patients, OSAS patients on chronic CPAP treatment and controls using the Scales for Outcome in Parkinson disease-Autonomic (SCOPA-AUT) questionnaire. All groups underwent autonomic function tests including head-up tilt test (HUTT), Valsalva maneuver, deep breathing, handgrip and cold face test. Twelve untreated OSAS, 17 OSAS on CPAP and 14 controls were studied. SCOPA-AUT total score was significantly higher in untreated OSAS compared with controls. The baseline values of systolic and diastolic blood pressure were significantly increased in untreated OSAS and in CPAP patients respectively, compared to controls. At HUTT, diastolic blood pressure changes were significantly higher in controls compared to both OSAS groups. Untreated OSAS showed a reduced response at deep-breathing compared to controls. Both OSAS groups had a significant reduction of reflex bradycardia at cold-face test. Treated and untreated OSAS patients complaint subjective autonomic symptoms reinforcing the close relationship between sleep and ANS. Cardiovascular reflexes indicate a tendency to hypertension and a reduced sensitivity to stimuli during wakefulness in both groups, suggesting a high risk of cardiovascular and cerebrovascular diseases.