Rapid Changes In Heart Rate Research Articles

Abstract Mo117: Investigation of Mechanisms to Modulate Contractility in 13-Lined Ground Squirrels

Introduction: During hibernation, 13-lined ground squirrels cycle between torpor and intermittent bouts of arousal (IBA). Bouts of IBA last 12-48 hours, during which heart rates rise from 2-4 bpm in torpor to 300 bpm during IBA before returning to torpor. Thus, rates of contractility and relaxation and their mechanisms must rapidly change. Phosphorylation of cardiac troponin I (cTnI) at serine 23/24 (pSer23/24) has been shown to decrease calcium sensitivity and increase the rate of myocardial relaxation, enabling faster heart rates. Heat shock protein 27 (HSP27) has been shown to protect contractility by stabilizing troponin. Hypothesis: We hypothesized that cTnI Ser23/24 phosphorylation would be higher in summer and IBA and that HSP27 would be found in higher quantities during torpor and IBA. Methods and Results: Left ventricular tissue (summer, n=8; torpor, n=8; IBA, n=8) was solubilized, separated by SDS-PAGE, and blotted with antibodies for quantification. The pSer23/24 to total troponin ratios were higher in summer compared to torpor (1.22±0.75 vs 0.32±0.19, p=0.003) and IBA (0.57±0.19, p=0.03), but not different between IBA and torpor. No significant season-dependence was observed for the serine 43 cTnI phosphorylation to total troponin ratio (torpor 1.45±0.69, summer 1.05±0.34, IBA 1.15±0.84). No significant season-dependence was observed in HSP27 (normalized to GAPDH) (summer 0.09±0.02, IBA 0.14±0.10, torpor 0.16±0.08). Nor was there a significant season-dependence observed in HSP90 (normalized to GAPDH) (summer 1.57±0.66, IBA 1.13±0.19, torpor 1.22±0.21). Conclusions: None of these mechanisms fully explain the rapid change in contractility observed during the hibernating periods of 13-lined ground squirrels. Other post-translational modifications of troponin or modifiers of HSP activity may modify the reported results. Such regulation may identify new treatments for humans where rapid changes in heart rate or contractility occur.

Wearable Multisensor Ring-Shaped Probe for Assessing Stress and Blood Oxygenation: Design and Preliminary Measurements

The increasing interest in innovative solutions for health and physiological monitoring has recently fostered the development of smaller biomedical devices. These devices are capable of recording an increasingly large number of biosignals simultaneously, while maximizing the user's comfort. In this study, we have designed and realized a novel wearable multisensor ring-shaped probe that enables synchronous, real-time acquisition of photoplethysmographic (PPG) and galvanic skin response (GSR) signals. The device integrates both the PPG and GSR sensors onto a single probe that can be easily placed on the finger, thereby minimizing the device footprint and overall size. The system enables the extraction of various physiological indices, including heart rate (HR) and its variability, oxygen saturation (SpO2), and GSR levels, as well as their dynamic changes over time, to facilitate the detection of different physiological states, e.g., rest and stress. After a preliminary SpO2 calibration procedure, measurements have been carried out in laboratory on healthy subjects to demonstrate the feasibility of using our system to detect rapid changes in HR, skin conductance, and SpO2 across various physiological conditions (i.e., rest, sudden stress-like situation and breath holding). The early findings encourage the use of the device in daily-life conditions for real-time monitoring of different physiological states.

Heart rate variability for the evaluation of patients with disorders of consciousness

ObjectiveClinical responsiveness of patients with a Disorder of Consciousness (DoC) correlates to sympathetic/parasympathetic homeostatic balance. Heart Rate Variability (HRV) metrics result in non-invasive proxies of modulation capabilities of visceral states. In this work, our aim was to evaluate whether HRV measures could improve the differential diagnosis between Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS) with respect to multivariate models based on standard clinical electroencephalography (EEG) labeling only in a rehabilitation setting. MethodsA prospective observational study was performed consecutively enrolling 82 DoC patients. Polygraphic recordings were performed. HRV-metrics and EEG descriptors derived from the American Clinical Neurophysiology Society's Standardized Critical Care terminology were included. Descriptors entered univariate and then multivariate logistic regressions with the target set to the UWS/MCS diagnosis. ResultsHRV measures resulted significantly different between UWS and MCS patients, with higher values being associated with better consciousness levels. Specifically, adding HRV-related metrics to ACNS EEG descriptors increased the Nagelkerke R2 from 0.350 (only EEG descriptors) to 0.565 (HRV-EEG combination) with the outcome set to the consciousness diagnosis. ConclusionsHRV changes across the lowest states of consciousness. Rapid changes in heart rate, occurring in better consciousness levels, confirm the mutual correlation between visceral state functioning patterns and consciousness alterations. SignificanceQuantitative analysis of heart rate in patients with a DoC paves the way for the implementation of low-cost pipelines supporting medical decisions within multimodal consciousness assessments.

Hypertension depresses arterial baroreflex control of both heart rate and cardiac output during rest, exercise, and metaboreflex activation.

Rapid regulation of arterial blood pressure on a beat-by-beat basis occurs primarily via arterial baroreflex control of cardiac output (CO) via rapid changes in heart rate (HR). Previous studies have shown that changes in HR do not always cause changes in CO, because stroke volume may vary. Whether these relationships are altered in hypertension is unknown. Using the spontaneous baroreflex sensitivity (SBRS) approach, we investigated whether baroreflex control of HR and CO were impaired after the induction of hypertension in conscious, chronically instrumented canines at rest, during mild exercise, and during exercise with metaboreflex activation (induced via reductions in hindlimb blood flow) both before and after induction of hypertension (induced via a modified Goldblatt approach-unilateral reduction in renal blood flow to ∼30% of control values until systolic pressure ≥ 140 mmHg and a diastolic pressure ≥ 90 mmHg for >30 days). After induction of hypertension, SBRS control of both HR and CO was reduced in all settings. In control, only about 50% of SBRS changes in HR caused changes in CO. This pattern was sustained in hypertension. Thus, in hypertension, the reduced SBRS in the control of HR caused reduced SBRS control of CO and this likely contributes to the increased incidence of orthostatic hypotension seen in hypertensive patients.

Pediatric Advanced Life Support in a Neonatal Context.

Pediatric Advanced Life Support in a Neonatal Context.

Abstract 433: Regulatory and Elastic Protein Modifications in the Myocardium of Hibernating 13-lined Ground Squirrels

The 13-lined ground squirrel exhibits remarkable cardiac adaptation during hibernation, periods of torpor being interrupted by repeated inter-bout arousal (IBA). During IBA heart rate rises from 2-4 bpm to as great as 300 bpm. This rise in heart rate occurs over just 5 hours and remains elevated for 12-24 hours before returning to the lower heart rate. With such rapid and marked changes in heart rate, and thus filling time, myocardial stiffness and relaxation must be regulated within a short timeframe. The objective of this work was to establish post-translational modifications (PTMs) in two proteins critical to myocardial stiffness and relaxation; titin and cardiac troponin I (TnI). It was specifically hypothesized that phosphorylation during IBA would be similar to that of summer tissue and distinct from tissue isolated during torpor. Left ventricular tissue (summer, n=9; torpor, n=10; IBA, n=7) was solubilized and separated by either 2-12% gradient SDS-Page (titin) or 12.5% SDS-PAGE (TnI). Total titin phosphorylation was measured via Pro-Q Diamond Phosphoprotein/SYPRO Ruby staining. PKA-specific TnI phosphorylation was quantified via western blotting, using a primary antibody specific to Ser 23,24. While there was a tendency toward decreased total titin phosphorylation in IBA, the difference was not significant. In contrast, there were significant group effects in PKA-specific TnI phosphorylation. Phospho-TnI/Total TnI ratios were lower in torpor when compared to summer (0.22±0.12 vs. 0.68±0.,34, p<0.05). While there was no significant difference between summer and IBA (0.62±0.35), the difference between torpor and IBA failed to reach significance. This data supports the hypothesis that rapid changes in heart rates are associated with changes in cardiac troponin-I phosphorylation, a modification that contributes to rapid rates of relaxation. Further dissection of site specific titin phosphorylation will be required to assess the extent to which PTM modify titin associated stiffness. Results from this work may have significant implications in our understanding of altered compliance in human heart failure.

Potential strategy for assessing QT/QTc interval for drugs that produce rapid changes in heart rate: Electrocardiographic assessment of the effects of intravenous remimazolam on cardiac repolarization.

AimsRemimazolam is a new, ultra‐short‐acting benzodiazepine developed for intravenous (IV) use during procedural sedation and in general anaesthesia. Two trials were conducted to characterize its effects on cardiac repolarization.MethodsA thorough QT/QTc (TQT) study assessed electrocardiography effects of therapeutic and supratherapeutic doses of remimazolam and midazolam. To investigate whether RR‐QT hysteresis effects due to rapid heart rate changes might have confounded the QTc assessments in the TQT trial, a second trial used continuous IV remimazolam infusion to achieve stable heart rates during periods of stable remimazolam plasma concentration.ResultsDuring the TQT, both compounds produced a 10–20‐beats/min increase in heart rate within 30 seconds, persisting for 5–10 minutes. Within 30 seconds, the upper bound of the 2‐sided 90% confidence interval for the placebo‐corrected change from baseline for QTcI (ΔΔQTcI) exceeded 10 ms for both doses of remimazolam (ΔΔQTcI 7.2 [3.2, 11.2] ms for the 10 mg dose and 10.4 [6.5, 14.3] ms for the 20 mg dose) as well as for the 7.5‐mg dose of midazolam (8.2 [4.4, 12.1] ms). At 2 minutes after IV bolus, the upper bound of the 2‐sided 90% confidence interval for ΔΔQTcI exceeded 10 ms only for the remimazolam 20‐mg dose (6.3 [2.3, 10.2] ms). During the second study, during periods of stable heart rate, remimazolam had no clinically significant effect on QTc (peak ΔΔQTcI 3.4 [−1.1, 7.6] ms).ConclusionRemimazolam does not prolong cardiac repolarization (QTc). The methods reported here may allow assessment of the QTc effects of other drugs given by IV bolus.

Novel zebrafish behavioral assay to identify modifiers of the rapid, nongenomic stress response.

When vertebrates face acute stressors, their bodies rapidly undergo a repertoire of physiological and behavioral adaptations, which is termed the stress response. Rapid changes in heart rate and blood glucose levels occur via the interaction of glucocorticoids and their cognate receptors following hypothalamic‐pituitary‐adrenal axis activation. These physiological changes are observed within minutes of encountering a stressor and the rapid time domain rules out genomic responses that require gene expression changes. Although behavioral changes corresponding to physiological changes are commonly observed, it is not clearly understood to what extent hypothalamic‐pituitary‐adrenal axis activation dictates adaptive behavior. We hypothesized that rapid locomotor response to acute stressors in zebrafish requires hypothalamic‐pituitary‐interrenal (HPI) axis activation. In teleost fish, interrenal cells are functionally homologous to the adrenocortical layer. We derived eight frameshift mutants in genes involved in HPI axis function: two mutants in exon 2 of mc2r (adrenocorticotropic hormone receptor), five in exon 2 or 5 of nr3c1 (glucocorticoid receptor [GR]) and two in exon 2 of nr3c2 (mineralocorticoid receptor [MR]). Exposing larval zebrafish to mild environmental stressors, acute changes in salinity or light illumination, results in a rapid locomotor response. We show that this locomotor response requires a functioning HPI axis via the action of mc2r and the canonical GR encoded by nr3c1 gene, but not MR (nr3c2). Our rapid behavioral assay paradigm based on HPI axis biology can be used to screen for genetic and environmental modifiers of the hypothalamic‐pituitary‐adrenal axis and to investigate the effects of corticosteroids and their cognate receptor interactions on behavior.

Response of QT interval in methadone maintenance treated patients to the rapid changes in heart rate provoked by brisk standing: Comparison to healthy controls and patients with long QT syndrome

BackgroundPatients on methadone maintenance therapy are somehow similar to patients with congenital long QT syndrome (LQTS) because they have malfunction of potassium channels caused by a drug that cannot be easily discontinued. We tested patients on methadone therapy with the “stand-up” test, which has been shown to unravel pathologic QT-prolongation in congenital long-QT patients. Methods“Stand-up” test results of methadone-users, healthy volunteers and congenital LQTS patients were compared. Methadone serum levels and doses were collected. The prognostic value of the test was evaluated after 4years of follow-up. ResultsThe QT-response of methadone-users to the “stand-up” test resembled that of healthy volunteers more than the response of LQTS-patients. Differences in the QTc of methadone treated patients and controls, which were statistically significant at baseline, became no longer significant after standing. Within 52months of follow-up, one patient had suffered unexplained death and one had documented ventricular tachycardia. ConclusionsThe QT-response of methadone-users to the “stand-up” test is similar to that of healthy volunteers, not to that of LQTS-patients.

Abstract 9687: Vagal Reflexes as a Simple Clinical Tool to Stratify Risk Among LQT1 Patients

Background We demonstrated that lower baroreflex sensitivity (BRS) values can identify Long QT Syndrome 1(LQT1) patients at lower risk for life-threatening arrhythmias, suggesting a protective role of “blunted” autonomic responses. However, the complexities of the phenylephrine method to assess BRS have limited its use for risk stratification in clinical practice. Objectives To identify an easily quantifiable marker of reflex vagal activation that might perform as well as BRS in predicting a differential risk for life-threatening arrhythmias in LQT1 patients. Specifically, to test the predictive value of heart rate (HR) recovery during the first minute after cessation of an exercise stress test. Methods In a South African LQT1 founder population segregating KCNQ1-A341V, 44 mutation carriers (MCs) underwent an exercise stress test and a phenylephrine test off-β-blockers. The HR decrease during the first minute of recovery from the peak of exercise (Δ 1min-rec ) was measured and subsequently correlated with BRS values among symptomatic (syncope, cardiac arrest, sudden death) and asymptomatic patients. Results Asymptomatic MCs had a smaller decrease in HR during the first minute of recovery from peak exercise (Δ 1min-rec ) than symptomatic MCs (13±5 vs 19±7 bpm, p< 0.05). A Δ 1min-rec <15 bpm, which corresponds to the first tertile of its distribution, predicted a much lower probability of being symptomatic (OR 0.13, 95%CI 0.028-0.63, p<0.05). The Δ 1min-rec values were significantly correlated with BRS values (r=0.64, p=0.001). Both tests performed similarly and quite accurately in discriminating between MCs with or without cardiac events (AUC 0.77 and 0.80). Conclusions LQT1 patients are at risk for life-threatening arrhythmias especially in association with rapid HR changes in either direction. Blunted autonomic responses, identified by lower values of BRS and - as vagal reflexes are concerned - by smaller HR reductions at the end of exercise, can usefully contribute to their risk stratification in a novel, simple, and inexpensive way.

A-Kinase Anchoring Proteins

The heart is a sophisticated organ that continuously pumps blood to ensure that oxygen and nutrients reach the brain, other organs, and peripheral tissue. The right side of the heart pumps blood to the lungs, where oxygen is taken up and carbon dioxide is removed. The left side of the heart then pumps blood to the rest of the body, where oxygen and nutrients are delivered to tissues. This cycle is sustained by the repeated contraction of cardiomyocytes, specialized muscle cells that are designed to contract and respond rapidly to physiological stimuli. Normally, contraction of atrial and ventricular myocytes is activated by action potentials that originate in the sinoatrial node in the wall of the right atrium, often referred to as the pacemaker of the heart. Coupling of this electric signal to contraction (EC coupling) in cardiac myocytes is initiated with Ca2+ influx through L-type Ca2+ channels, which activates intracellular Ca2+ release via ryanodine receptors located in the sarcoplasmic reticulum (SR) and thus induces a global increase in [Ca2+]i that triggers contraction.1,2 The rate at which the sinoatrial node myocytes fire action potentials is modulated by 2 opposing nervous systems. The sympathetic nervous system uses the catecholamine hormones noradrenaline and adrenaline to increase the force and rate of atrial and ventricular contraction. In contrast, the parasympathetic nervous system releases the neurotransmitter acetylcholine to reduce action potentials from the sinoatrial node. Together, these neural systems ensure that cardiac output is matched to the physiological needs of the organism, a process that is often termed “stimulus-response coupling.” Although numerous signal-transduction cascades are operational in cardiomyocytes, G-protein–coupled receptor–signaling pathways play a prominent role. Agonists such as noradrenaline, adrenaline, angiotensin II, and endothelin-1 promote the interaction of their respective receptors with a G-protein heterotrimer comprising α-, β-, …

Cardiac Ion Channels

The analysis of the molecular basis of the inherited cardiac arrhythmias has been the driving force behind the identification of the ion channels that generate the action potential. The genes encoding all the major ion channels have cloned and sequenced. The studies have revealed greater complexity than heretofore imagined. Many ion channels function as part of macromolecular complexes in which many components are assembled at specific sites within the membrane. This review describes the generation of the normal cardiac action potential. The properties of the major ionic currents are the examined in detail. Special emphasis is placed on the functional consequences of arrhythmia-associated ion channel mutations. The review concludes with a glimpse of the directions in which this new electrophysiology may lead. The normal sequence and synchronous contraction of the atria and ventricles require the rapid activation of groups of cardiac cells. An activation mechanism must enable rapid changes in heart rate and also respond to the changes in autonomic tone. The propagating cardiac action potential fulfils these roles. Figure 1 illustrates the 5 phases of the normal action potential: 1. Phase 4, or the resting potential, is stable at ≈−90 mV in normal working myocardial cells. 2. Phase 0 is the phase of rapid depolarization. The membrane potential shifts into positive voltage range. This phase is central to rapid propagation of the cardiac impulse (conduction velocity, θ=1 m/s). 3. Phase 1 is a phase of rapid repolarization. This phase sets the potential for the next phase of the action potential. 4. Phase 2, a plateau phase, is the longest phase. It is unique among excitable cells and marks the phase of calcium entry into the cell. 5. Phase 3 is the phase of rapid repolarization that restores the membrane potential to its resting value.1 Figure 1. Membrane currents that generate the a normal …

Neural Control of Heart Rate Is an Arrhythmia Risk Modifier in Long QT Syndrome

The purpose of this study was to test the hypothesis that differences in autonomic responses might modify clinical severity in long QT syndrome type 1 (LQT1) patients, those with KCNQ1 mutations and reduced I(Ks), in whom the main arrhythmia trigger is sympathetic activation. Some long QT syndrome (LQTS) patients experience life-threatening cardiac arrhythmias, whereas others remain asymptomatic throughout life. This clinical heterogeneity is currently unexplained. In a South African LQT1 founder population segregating KCNQ1-A341V, we correlated major cardiac events to resting heart rate (HR) and to baroreflex sensitivity (BRS) on and off beta-adrenergic blockers (BB). In 56 mutation carriers (MCs), mean HR was lower among asymptomatic patients (p < 0.05). Among MCs with a QT interval corrected for heart rate <or=500 ms, those in the lower HR tertile were less likely to have suffered prior cardiac events (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.04 to 0.79, p < 0.02). The BRS was lower among asymptomatic than symptomatic MCs (11.8 +/- 3.5 ms/mm Hg vs. 20.1 +/- 10.9 ms/mm Hg, p < 0.05). A BRS in the lower tertile was associated with a lower probability of being symptomatic (OR 0.13, 95% CI 0.02 to 0.96, p < 0.05). A similar trend was observed during BB. The MCs in the lower tertile for both HR and BRS were less frequently symptomatic than MCs with different patterns (20% vs. 76%, p < 0.05). Subjects with either ADRA2C-Del322-325 or homozygous for ADRB1-R389, 2 polymorphisms predicting enhanced adrenergic response, were more likely to have BRS values above the upper tertile (45% vs. 8%, p < 0.05). Lower resting HR and "relatively low" BRS are protective factors in KCNQ1-A341V carriers. A plausible underlying mechanism is that blunted autonomic responses prevent rapid HR changes, arrhythmogenic when I(Ks) is reduced. These findings help understanding phenotypic heterogeneity in LQTS and identify a physiological risk modifier, which is probably genetically determined.

Control of rapid heart rate changes for electrocardiographic analysis: implications for thorough QT studies

Following an abrupt change in heart rate (HR), QT adaptation is achieved within a delayed time frame. The exclusion of electrocardiograms (ECGs) showing rapid HR changes influences the level of a drug-induced QT prolongation. Continuous 12-lead ECG-Holter monitoring was performed in 31 healthy subjects. Using the "bin" method, we evaluated moxifloxacin effects on (1) QT interval duration at different RR intervals and (2) on the rate dependence of QT interval. These endpoints were calculated separately for five types of ECG analysis: classification of cardiac complexes based on (a) the single preceding RR interval (RR-1) and (b) RR filters excluding rapid HR changes according to the formula RR-1 = RR[time-window] +/- threshold, where the time-window could be 30 or 60 s (R30 and R60) and the threshold 15 or 30 ms (th15 or th30). Moxifloxacin-induced QT prolongation was consistently higher using the stable models when compared with the RR-1 model. Moxifloxacin-induced QT prolongation at RR = 1000 ms was 8.2 +/- 11.2 vs. 10.9 +/- 10.4 ms using the RR-1 and R60th15 stable models, respectively (p < 0.05). Moxifloxacin-induced QT prolongation was more pronounced at slow than at fast HR. This so-called "reverse rate-dependent" effect was more pronounced when assessed using stable HR models (0.023 IC95% [0.019;0.027] vs. 0.015 IC95% [0.012;0.017] using the RR-1 model). The exclusion of ECGs with rapid HR changes influences the magnitude of drug-induced QT changes. The hysteresis phenomenon should not be neglected when dedicated QT studies are performed.

Age and gender effects on heart rate activation associated with periodic leg movements in patients with restless legs syndrome.

Periodic leg movements during sleep (PLMS) are often associated with electroencephalographic (EEG) changes, such as microarousals (MA), and with heart rate (HR) variations. The aim of the present study was to evaluate the effects of age and gender on HR changes associated with PLMS in restless legs syndrome (RLS) patients. Forty-two RLS patients underwent one night of polysomnographic recordings. They were divided into 3 groups of 14 subjects (7 women and 7 men) according to age, i.e. young (25-40 years), middle-aged (41-55 years) and elderly (56-71 years) patients. The RR interval was calculated for 5 intervals before and 15 intervals after the onset of 50 PLMS in each patient. PLMS were associated with HR changes characterized by a tachycardia followed by a bradycardia. However, a reduction in the tachycardia and the bradycardia was observed with age. Moreover, women showed a higher amplitude in the bradycardia than men. No age or gender difference was found for MA index and duration. This study showed age and gender differences in the magnitude of the HR changes associated with PLMS. The knowledge of HR variations during sleep, including rapid HR changes associated with sleep events such as PLMS or MA, may be helpful in understanding the potential mechanisms involved in the increased cardiac risk observed in elderly.

Dynamics of swallowing-induced cardiac chronotropic responses in healthy subjects.

Simultaneous recording of ECG and swallowing movements in healthy humans (n=23, age 20-57 years) showed that each swallow is accompanied by transient tachycardia with initial abrupt and pronounced heart rate increase. These rapid changes in heart rate (evaluation by maximum increment of heart rate over two successive heartbeats, Delta HR(2bt)) are typical of vagal chronotropic responses. The amplitude of tachycardia induced by a single swallow was significantly higher in the supine position (13.1 +/- 5.6 bpm) compared to the standing position (8.5 +/- 3.8 bpm; p<0.0001). Chronotropic responses to a series of three or more successive swallows consisted of two phases, the initial abrupt acceleration and subsequent slower growth of heart rate. In the standing position, the portion of the first rapid phase significantly decreased, while the portion of the slower phase increased compared to the supine position. The amplitude of tachycardia induced by a single swallow and parameter Delta HR(2bt) can serve as indices of the strength of parasympathetic modulation of the heart. By contrast, further slow increase in the heart rate determined by summation of responses to a series of successive swallows can result from not only inhibition of the parasympathetic influences, but also enhancement of sympathetic activity during swallowing.

Real-time measurement of cardiac vagal tone in conscious dogs.

Rapid changes in heart rate are caused by changes in parasympathetic tone. The NeuroScope is an electronic device designed to offer an objective real-time measure of instantaneous cardiac vagal tone by phase demodulation of a high-resolution time domain of R-R wave intervals. Data are displayed against an arbitrary but linear scale, the cardiac index of parasympathetic activity (CIPA). To validate this method, 10 conscious healthy dogs were each given six incremental doses of atropine (0.01 mg/kg) to a total dose of 0.06 mg/kg or equal volumes of saline. A dose-response curve was constructed. At the maximum dose of atropine, CIPA values fell to 1. 3 +/- 0.7% (SD) of baseline, whereas R-R intervals fell to 51.5 +/- 11.5% of baseline, and standard deviation of the R-R wave interval fell to 10.6 +/- 6.5% of baseline. These findings show that the NeuroScope can provide a specific real-time index of cardiac vagal tone in dogs without need for recourse to atropine.

Evaluation of heart rate changes: electrocardiographic versus photoplethysmographic methods.

The heart rate (HR) variation to forced deep breathing (HRDB) and to the Valsalva maneuver (Valsalva ratio; VR) are the two most widely used tests of cardiovagal function in human subjects. The HR is derived from a continuously running electrocardiographic (ECG) recording. Recently, HR derived from the arterial waveform became available on the Finapres device (FinapHR), but its ability to detect rapid changes in HR remains uncertain. We therefore evaluated HRDB and VR derived from FinapHR using ECG-derived HR (ECGHR) recordings as the standard. We also compared the averaged HR on Finapres (Finapav) with beat-to-beat Finapres (FinapBB) values. Studies were undertaken in 12 subjects with large HR variations: age, 34.5 +/- 9.3 (SD) years; six males and six females. FinapBB values were superimposable upon ECGHR for both HRDB and VR. In contrast, Finapav failed to follow ECGHR for HRDB and followed HRECG with a lag for the VR. To evaluate statistically how closely FinapHR approximated ECGHR, we undertook regression analysis, using mean values for each subject. To compare the two methods, we evaluated the significance of the difference between test and standard values. For HRDB, FinapBB reproducibly recorded HR (R2 = 0.998), and was significantly (p = 0.001) better than Finapav (R2 = 0.616; p < 0.001). For VR, HRBB generated a VR that was not significantly different from the correct values, while HRav generated a value that was slightly but consistently lower than the correct values (p < 0.001). We conclude that FinapHR reliably records HR variations in the beat-to-beat mode for cardiovascular HR tests.

Control of blood pressure and heart rate in patients randomized to epidural or general anesthesia for lower extremity vascular surgery

Study Objective: To examine the degree of success at maintaining patients randomized to epidural or general anesthesia for peripheral vascular surgery within predetermined blood pressure (BP) and heart rate (HR) limits. To investigate associations between such hemodynamic control and intraoperative myocardial ischemia and postoperative major cardiac morbidity. Design: Prospective randomized clinical trial. Setting: University-affiliated hospital. Patients: 100 patients undergoing elective lower extremity revascularization for atherosclerotic peripheral vascular disease. Interventions: Patients were randomized to receive either epidural anesthesia or general anesthesia. Blood pressure and HR limits were determined prior to randomization. Hemodynamic monitoring and management of anesthesia was standardized. Myocardial ischemia and major cardiac morbidity were diagnosed by a blinded cardiologist, based on continuous ambulatory ECG monitoring, cardiac enzymes, and 12 lead ECGs. Intraoperative BP and HR data were analyzed by investigators masked to the type of anesthesia given. Measurements and Main Results: A greater percentage of patients randomized to general anesthesia had intraoperative BPs more above their limit (95% vs. 72%, p = 0.002) and/or more rapid changes in HR (75% vs. 48%, p = 0.008) or BP (100% vs. 93%, p = 0.04) than those randomized to epidural anesthesia. Intraoperative ischemia and major cardiac morbidity were similar in the two anesthesia groups. Patients experiencing intraoperative ischemia, regardless of anesthetic type, more frequently had BPs greater than 10% above their upper limit (90% vs. 60%, p = 0.04) and/or more rapid HR changes (90% vs. 58%, p = 0.03) compared with patients without ischemia. These vital sign abnormalities, however, were not necessarily temporally related to the ischemic episodes. Patients experiencing subsequent major cardiac morbidity were not different from other patients with respect to excursions out of BP or HR limits. Conclusions: Prevention of elevated intraoperative BP and/or rapid changes in BP or HR may be more successful with epidural than with general anesthesia. Such vital sign abnormalities may occur more frequently in patients who have had intraoperative ischemia or are at risk for having it later in the procedure.

Sleep and Cardiac Rhythm in Healthy Men

Cardiac rhythm during sleep was analysed in 168 healthy men aged 19 to 30 (mean 21.8) years using continuous nocturnal ECG recordings. Thirty five of the subjects were endurance athletes; 99 were recorded at home and 69 at a garrison during military service. The number of short term (less than one min) accelerations of heart rate of more than ten beats per minute ranged from 1.3 to 14.3 per hour; the number or accelerations (greater than one min) of more than 25 beats per minute typical of nocturnal restlessness ranged from zero to 6.1 per hour. The accelerations indicating nocturnal restlessness were more common during recordings done at the garrison than at home (2.2 per hour vs 1.3 per hour, P less than 0.01), whereas the short term accelerations were not (5.8 per hour vs 5.1 per hour, NS). Sinus pauses exceeding 2.00 sec occurred in 17 men (13 in athletes), occasional second degree atrioventricular block in 19 (eight in athletes) and ventricular premature beats in 37. Eighty-two per cent of sinus pauses, 83% of second degree atrioventricular blocks, and 81% of ventricular premature beats (when less than ten in the same subject) were associated with short term changes in heart rate. In conclusion, rapid changes in heart rate, presumably as a results of autonomic activation, are closely associated with most arrhythmias in healthy men during sleep, whereas changes in heart rate typical of nocturnal restlessness have little arrhythmogenic effect.