High-frequency Heart Rate Research Articles

Contribution of haemodynamic side effects and associated autonomic reflexes to ventricular arrhythmias triggering by torsadogenic hERG blocking drugs.

Background and PurposeHERG blocking drugs known for their propensity to trigger Torsades de Pointes (TdP) were reported to induce a sympatho‐vagal coactivation and to enhance High Frequency heart rate (HFHR) and QT oscillations (HFQT) in telemetric data. The present work aimed to characterize the underlying mechanism(s) leading to these autonomic changes.Experimental ApproachEffects of 15 torsadogenic hERG blocking drugs (astemizole, chlorpromazine, cisapride, droperidol, ibutilide, dofetilide, haloperidol, moxifloxacin, pimozide, quinidine, risperidone, sotalol, sertindole, terfenadine, and thioridazine) were assessed by telemetry in beagle dogs. Haemodynamic effects on diastolic and systolic arterial pressure were analysed from the first doses causing QTc prolongation and/or HFQT oscillations enhancement. Autonomic control changes were analysed using the high frequency autonomic modulation (HFAM) model.Key ResultsExcept for moxifloxacin and quinidine, all torsadogenic hERG blockers induced parasympathetic activation or sympatho‐vagal coactivation combined with enhancement of HFQT oscillations. These autonomic effects result from reflex compensatory mechanisms in response to mild haemodynamic side effects. These haemodynamic mechanisms were characterized by transient HR acceleration during HF oscillations. A phenomenon of concealed QT prolongation was unmasked for several torsadogenic hERG blockers under β‐adrenoceptor blockade with atenolol. Resulting enhancement of HFQT oscillations was shown to contribute directly to triggering dofetilide‐induced ventricular arrhythmias.Conclusion and ImplicationsThis work supports for the first time a contribution of haemodynamic side properties to ventricular arrhythmias triggered by torsadogenic hERG blocking drugs. These haemodynamic side effects may constitute a second component of their arrhythmic profile, acting as a trigger alongside their intrinsic arrhythmogenic electrophysiological properties.

High-Frequency Heart Rate Variability Index: A Prospective, Observational Trial Assessing Utility as a Marker for the Balance Between Analgesia and Nociception Under General Anesthesia.

Maintaining a balance between nociception and analgesia perioperatively reduces morbidity and improves outcomes. Current intraoperative analgesic strategies are based on subjective and nonspecific parameters. The high-frequency heart rate (HR) variability index is purported to assess the balance between nociception and analgesia in patients under general anesthesia. This prospective observational study investigated whether intraoperative changes in the high-frequency HR variability index correlate with clinically relevant nociceptive stimulation and the addition of analgesics. Instantaneous and mean high-frequency HR variability indexes were measured continuously in 79 adult subjects undergoing general anesthesia for laparoscopic cholecystectomy. The indexes were compared just before and 2 minutes after direct laryngoscopy, orogastric tube placement, first skin incision, and abdominal insufflation and just before and 6 minutes after the administration of IV hydromorphone. Data from 65 subjects were included in the final analysis. The instantaneous index decreased after skin incision ([SEM], 58.7 [2.0] vs 47.5 [2.0]; P < .001) and abdominal insufflation (54.0 [2.0] vs 46.3 [2.0]; P = .002). There was no change in the instantaneous index after laryngoscopy (47.2 [2.2] vs 40.3 [2.3]; P = .026) and orogastric tube placement (49.8 [2.3] vs 45.4 [2.0]; P = .109). The instantaneous index increased after hydromorphone administration (58.2 [1.9] vs 64.8 [1.8]; P = .003). In adult subjects under general anesthesia for laparoscopic cholecystectomy, changes in the high-frequency HR variability index reflect alterations in the balance between nociception and analgesia. This index might be used intraoperatively to titrate analgesia for individual patients. Further testing is necessary to determine whether the intraoperative use of the index affects patient outcomes.

Abstract # 3199 Differences in Endothelial Progenitor Cell Outgrowth and Cardio-autonomic Function with Hypertension and HIV Disease Comorbidity

Peripheral blood mononuclear cell derived endothelial progenitor cells (EPCs) are associated with cardiovascular function and their numbers decline with older age hypertensive risk and HIV infectionisease burden. Emergent evidence suggests that their functionality and presence may be related to cardio-autonomic and psychological functioning. This study examined whether in a sample of post-menopausal (PM) women (n = 5 HIV+/HTN + mean PM age = 53, n = 11 HIV+/HTN- mean PM age = 57, n = 6 HIV-/HTN + mean PM age = 53, or n = 14 HIV-/HTN- mean PM age = 53) ex vivo expansion of EPC counts derived from peripheral blood mononuclear cells covary with measures of high and low frequency heart rate variability. Mononuclear cells were isolated from each subject’s blood sample and incubated for 15 days in a fibronectin coated flask at 37 degrees Celsius, with the EPC medium changed every 2–3 days. Total cell, cluster, and spindle counts were recorded every 5 days for 2 weeks at 3 different time points labeled (t1, t2, and t3). After 10 days, EPC counts were significantly lower in HIV + HTN + and HIV + HTN- women compared to HIV-HTN+ (ps

Do Changes in Hemodynamic Parameters Depend Upon Length of Sleep Deprivation? Comparison Between Subjects With Normal Blood Pressure, Prehypertension, and Hypertension.

The main objective of the study was to analyze the impact of sleep deprivation upon hemodynamic and autonomic parameters in subjects with normal blood pressure (BP) compared to prehypertension and hypertension at 24, 28, and 32 h of total sleep deprivation (TSD). Thirty volunteers, healthy men with current medical tests indicating the absence of disease took part in the study. After physical examination (basic neurological, clinical examination, echocardiography and doppler ultrasound of the renal arteries, evaluation of the autonomic nervous system) subjects were divided into three groups: I – normotensive, II – pre-hypertensive, III – hypertensive (age: 31.2 ± 2.1 vs. 33.5 ± 2.7 vs. 36.8 ± 2.7 years, p > 0.05; BMI: 25.2 ± 0.8 vs. 29.0 ± 1.5 vs. 26.4 ± 1.0 kg/m2, p > 0.05). Hemodynamic and autonomic parameters were automatically measured at rest and in a tilted position with a Task Force Monitor. The Task Force Monitor consists of electrocardiography, impedance cardiography, oscillometric, and continuous BP measurement. Mixed models with random effects was applied in order to analyze the parameters’ dependence on the time and the group of patients. One-way ANOVA or Kruskal–Wallis test were used to detect differences between normotensive, pre-hypertensive and hypertensive groups in each time point. In the pre-hypertensive group 28-h TSD resulted in increased vagal outflow [changes in high frequency heart rate (HR) variability, p = 0.0189], as evidenced by decreased HR (p = 0.0293). Moreover after 24-h TSD and 28-h TSD we observed changes in BP parameters. In hypertensive group, the most important changes in hemodynamic parameters: systolic blood pressure (sBP, p = 0.0031), diastolic blood pressure (dBP, p = 0.0136), cardiac output (CO, p = 0.0439) and changes in HR (p = 0.0063) after tilt test were observed after 32-h TSD. In conclusion, our results show that changes in hemodynamic parameters during sleep deprivation depend on the baseline BP and duration of TSD. What is important, both groups reported a decrease of sBP and dBP during the TSD (pre-hypertensive group after 24, 28-h TSD; hypertensive group after 32-h TSD. In our opinion, this is the first study which considers three homogenous groups in terms of gender: only men, during different points of acute TSD: 24, 28, and 32 h of TSD in laboratory condition.

Autonomic responses to physiological stressors in women with type 2 diabetes

To compare autonomic function, measured during handgrip (HG) and cold pressor (CP), between obese with and without type 2 diabetes and non-obese women in fasting and post-glucose load states. Twelve obese women with type 2 diabetes (50 +/- 1 years), 15 obese women without type 2 diabetes (48 +/- 2 years), and 12 non-obese women (49 +/- 2 years) participated in this study. Heart rate variability (HRV) was determined during autonomic function tests, conducted in both the fasting state and after a glucose challenge (oral glucose tolerance test-OGTT). Obese women with and without diabetes and non-obese women responded similarly fasted and post-glucose challenge, such that in the fasted state low frequency power normalized (LF(nu)) to total power (TP), log transformed (Ln) low frequency to high frequency ratio (LnLF/HF) and heart rate (HR) significantly increased with the autonomic functional tasks (P < 0.05), whereas HF(nu) significantly decreased with the tasks (P < 0.05). Handgrip elicited a lower LnTP and a higher HR (P < 0.05) when compared to CP in the fasted state. In the glucose challenged state LF(nu), LnLF/HF and HR increased (P < 0.05) and HF(nu) significantly decreased (P < 0.05). Results of autonomic testing did not differ between obese women, with and without diabetes, and non-obese women. The HG test elicited a greater reduction in HRV total power compared to the CP. This suggests that HG may be more useful when examining autonomic function in women with complicated diabetes.

Sevoflurane anesthesia decreases cardiac vagal activity and heart rate variability

We evaluated cardiac vagal activity during sevoflurane anesthesia in neurosurgical patients. Heart rate variability was determined by power spectral analysis and entropy with the patient awake and during sevoflurane anesthesia. High frequency power (0.15-0.50 Hz) and heart rate entropy decreased during sevoflurane and these effects were significantly correlated (r = 0.71 +/- 0.12, P < 0.05). The results confirm that cardiac vagal activity was the primary determinant of heart rate variability, which was attenuated by sevoflurane.

Respiratory sinus arrhythmia, cardiac vagal control, and daily activity.

Ambulatory respiratory sinus arrhythmia (RSA) or high-frequency heart rate (HR) variability is frequently employed as an index of cardiac parasympathetic control and related to risk or severity of cardiovascular disease. However, laboratory studies indicate variations in physical activity and respiratory parameters of rate and tidal volume may confound estimation of vagal activity. Because little is known about these relations outside the laboratory, we examined ambulatory relations among RSA, respiration, physical activity, and HR during waking hours by employing a multichannel monitoring system. Forty healthy young-to-middle aged adults underwent daytime monitoring that included continuous registration of the ECG, respiration (inductance plethysmography), and accelerometry motion activity. Within-individual regression analyses were performed to examine minute-to-minute relations between RSA and respiration, HR, and indexes of physical activity (minute ventilation and motion). HR changes were assumed to be strongly related to within-individual variations of vagal tone. RSA adjusted for respiratory parameters and unadjusted RSA were compared for strength of prediction of other measures. Unadjusted RSA was related to respiratory parameters (R = 0.80) and moderately predicted minute-to-minute HR and activity variances (means = 56%, HR; 48%, minute ventilation; and 37%, motion). Adjusted RSA predicted significantly more HR and activity variance (means = 75%, 76%, and 57%, respectively) with narrower confidence intervals. We conclude that ambulatory RSA magnitude is associated with respiratory variations and physical activity. Adjustment for respiratory parameters substantially improves relations between RSA and significantly vagally mediated HR and physical activity. Concurrent monitoring of respiration and physical activity may enhance HR variability accuracy to predict autonomic control.