A pilot investigation of the effect of extremely low frequency pulsed electromagnetic fields on humans' heart rate variability

The question whether pulsed electromagnetic field (PEMF) can affect the heart rhythm is still controversial. This study investigates the effects on the cardiocirculatory system of ELF-PEMFs. It is a follow-up to an investigation made of the possible therapeutic effect ELF-PEMFs, using a commercially available magneto therapeutic unit, had on soft tissue injury repair in humans. Modulation of heart rate (HR) or heart rate variability (HRV) can be detected from changes in periodicity of the R-R interval and/or from changes in the numbers of heart-beat/min (bpm), however, R-R interval analysis gives only a quantitative insight into HRV. A qualitative understanding of HRV can be obtained considering the power spectral density (PSD) of the R-R intervals Fourier transform. In this study PSD is the investigative tool used, more specifically the low frequency (LF) PSD and high frequency (HF) PSD ratio (LF/HF) which is an indicator of sympatho-vagal balance. To obtain the PSD value, variations of the R-R time intervals were evaluated from a continuously recorded ECG. The results show a HR variation in all the subjects when they are exposed to the same ELF-PEMF. This variation can be detected by observing the change in the sympatho-vagal equilibrium, which is an indicator of modulation of heart activity. Variation of the LF/HF PSD ratio mainly occurs at transition times from exposure to nonexposure, or vice versa. Also of interest are the results obtained during the exposure of one subject to a range of different ELF-PEMFs. This pilot study suggests that a full investigation into the effect of ELF-PEMFs on the cardiovascular system is justified.     

Microgravity alters respiratory sinus arrhythmia and short-term heart rate variability in humans

We studied heart rate (HR), heart rate variability (HRV), and respiratory sinus arrhythmia (RSA) in four male subjects before, during, and after 16 days of spaceflight. The electrocardiogram and respiration were recorded during two periods of 4 min controlled breathing at 7.5 and 15 breaths/min in standing and supine postures on the ground and in microgravity. Low (LF)- and high (HF)-frequency components of the short-term HRV (< or =3 min) were computed through Fourier spectral analysis of the R-R intervals. Early in microgravity, HR was decreased compared with both standing and supine positions and had returned to the supine value by the end of the flight. In microgravity, overall variability, the LF-to-HF ratio, and RSA amplitude and phase were similar to preflight supine values. Immediately postflight, HR increased by approximately 15% and remained elevated 15 days after landing. LF/HF was increased, suggesting an increased sympathetic control of HR standing. The overall variability and RSA amplitude in supine decreased postflight, suggesting that vagal tone decreased, which coupled with the decrease in RSA phase shift suggests that this was the result of an adaptation of autonomic control of HR to microgravity. In addition, these alterations persisted for at least 15 days after return to normal gravity (1G).     

Sleep processes exert a predominant influence on the 24-h profile of heart rate variability

Adverse cardiovascular events are known to exhibit 24-h variations with a peak incidence in the morning hours and a nonuniform distribution during the night. The authors examined whether these 24-h variations could be related to circadian or sleep-related changes in heart rate (HR) and in HR variability (HRV). To differentiate the effect of circadian and sleep-related influences, independent of posture and of meal ingestion, seven normal subjects were studied over 24 h, once with nocturnal sleep from 2300 to 0700 h and once after a night of sleep deprivation followed by 8 h of daytime sleep from 0700 to 1500 h. The subjects were submitted to constant conditions (continuous enteral nutrition and bed rest). HRV was calculated every 5 min using two indexes: the standard deviation of normal R-R intervals (SDNN) and the ratio of low-frequency to low-frequency plus high-frequency power. Sleep processes exerted a predominant influence on the 24-h profiles of HR and HRV, with lowest HRV levels during slow wave sleep, high levels during REM sleep and intrasleep awakenings, and abrupt increases in HR at each transition from deeper sleep to lighter sleep or awakenings. The circadian influence was smaller, except for SDNN, which displayed a nocturnal increase of 140% whether the subjects slept or not. This study demonstrates that 24-h variations in HR and HRV are little influenced by the circadian clock andare mainly sleep-stage dependent. The results suggest an important role for exogenous factors in the morning increase in cardiovascular events. During sleep, the sudden rises in HR at each transition from deeper sleep to lighter sleep or awakenings might precipitate the adverse cardiac events.     

Effect of targeted deletions of beta1- and beta2-adrenergic-receptor subtypes on heart rate variability

Beta-adrenergic receptors (beta-ARs) play a major role in regulating heart rate (HR) and contractility in the intact cardiovascular system. Three subtypes (beta1, beta2, and beta3) are expressed in heart tissue, and the role of each subtype in regulating cardiac function has previously been determined by using both pharmacological and gene-targeting approaches. However, previous studies have only examined the role of beta-ARs in the macrolevel regulation of HR. We employed three knockout (KO) mouse lines, beta1-KO, beta2-KO, and beta1/beta2 double KO (DL-KO), to examine the role that beta-AR subtypes play in HR variability (HRV) and in the sympathetic and parasympathetic inputs into HR control. Fast Fourier transformation (FFT) in frequency domain methods of ECG spectral analysis was used to resolve HRV into high- and low-frequency (HF and LF) powers. Resting HR (in beats/min) was decreased in beta1-KO [488 (SD 27)] and DL-KO [495 (SD 12)] mice compared with wild-type [WT; 638 (SD 30)] or beta2-KO [656 (SD 51)] (P < 0.0005) mice. Mice lacking beta1-ARs (beta1-KO and DL-KO) had increased HRV (as illustrated by the standard deviation of normal R-R intervals) and increased normalized HF and LF powers compared with mice with intact beta1-ARs (WT and beta2-KO). These results demonstrate the differential role of beta-AR subtypes in regulating autonomic signaling.     

The relationship between respiratory sinus arrhythmia and heart rate during anesthesia in rat.

During inspiration the heart rate (HR) increases and during expiration it decreases. Contribution of respiratory sinus arrhythmia (RSA) to spontaneous heart rate variability (HRV) can be measured as the high frequency (HF) component of variation in consecutive R-R intervals on ECG. In conscious rats, slowing of HR is associated with an increase in HF. The aim of this study was to investigate whether this relationship between HF and HR is preserved during anesthesia in rat. A 15 minutes long ECG signal was recorded from rats (N=15) under moderate chloral hydrate (CHL) anesthesia. Recordings were extended with 45 minutes to investigate the effect of atropine (N=3), against controls (N=3). Short term HRV was investigated in 30 seconds long epochs. HF was considered the frequency band between 0.8 and 1.6 Hz. RSA was quantified as the relative spectral power of the HF. Respiratory frequency (RF) was quantified as the mean spectral frequency within the HF band. One minute estimates of HR, RSA and HF were calculated by averaging 3 epochs of 30 seconds overlapped 50%. The average HR was 427 +/- 3 bpm. The magnitude of RSA was 45 +/- 1% at a RF of 71 +/- 1 rpm. We found that: (1) the decrease in HR that occurs during CHL anesthesia in rat correlates with an increase in RSA; (2) atropine reduces RSA and the time-dependent decrease in HR; (3) the time-dependent increase in RSA is preserved after atropine. We conclude that the correlation between RSA and HR reflects the cardio-pulmonary coupling under parasympathetic control.     

Heart rate dynamics in iNOS knockout mice

Nitric oxide has both an inhibitory and excitatory role in the regulation of pre-ganglionic sympathetic neurons, involving the iNOS and nNOS systems respectively. The aim of the present study was to examine cardiovascular autonomic activity in iNOS knockout mice using spectral analysis of heart rate variability (HRV), and to determine the role of iNOS in altered HRV in endotoxaemia. Electrocardiograms were recorded in anaesthetised mice, and the R-R intervals digitized for spectral analysis of HRV and cardiac rhythm regularity using sample entropy analysis. The basal heart rate was higher in iNOS knockout mice compared with controls (465+/-8 vs 415+/-13 beat/min P<0.05), with a significant increase in the low frequency power of HRV spectra in iNOS knockout mice compared with controls (49.4+/-4.3 vs 33.8+/-5.6 normalized units, P<0.05), consistent with increased cardiac sympathetic activity. Endotoxaemia is known to decrease HRV, but the role of iNOS is unknown. LPS (20 mg/kg i.p) increased basal heart rate in both wild type and iNOS knockout mice, but caused a depression of HRV and sample entropy in both groups. Studies in isolated beating atria showed that the changes of HRV under basal or post-LPS conditions disappeared in vitro, suggesting that the autonomic system is responsible for altered HRV. We conclude that disruption of iNOS gene leads to an increase in the low frequency power of HRV consistent with increased cardiac sympathetic activity. These data also demonstrate that LPS-induced decrease of HRV is independent of iNOS.     

Assessment of parasympathetic reactivation after exercise

The objective of this study was to evaluate whether heart rate variability (HRV) can be used as an index of parasympathetic reactivation after exercise. Heart rate recovery after exercise has recently been shown to have prognostic significance and has been postulated to be related to abnormal recovery of parasympathetic tone. Ten normal subjects [5 men and 5 women; age 33 +/- 5 yr (mean +/- SE)] exercised to their maximum capacity, and 12 subjects (10 men and 2 women; age 61 +/- 10 yr) with coronary artery disease exercised for 16 min on two separate occasions, once in the absence of atropine and once with atropine (0.04 mg/kg) administered during exercise. The root mean square residual (RMS), which measures the deviation of the R-R intervals from a straight line, as well as the standard deviation (SD) and the root mean square successive difference of the R-R intervals (MSSD), were measured on successive 15-, 30-, and 60-s segments of a 5-min ECG obtained immediately after exercise. In recovery, the R-R interval was shorter with atropine (P < 0.0001). Without atropine, HRV, as measured by the MSSD and RMS, increased early in recovery from 4.1 +/- 0.4 and 3.7 +/- 0.4 ms in the first 15 s to 7.2 +/- 1.0 and 7.4 +/- 0.9 ms after 1 min, respectively (P < 0.0001). RMS (range 1.7-2.1 ms) and MSSD were less with atropine (P < 0.0001). RMS remained flat throughout recovery, whereas MSSD showed some decline over time from 3.0 to 2.2 ms (P < 0.002). RMS and MSSD were both directly related (r(2) = 0.47 and 0.56, respectively; P < 0.0001) to parasympathetic effect, defined as the difference in R-R interval without and with atropine. In conclusion, RMS and MSSD are parameters of HRV that can be used in the postexercise recovery period as indexes of parasympathetic reactivation after exercise. These tools may improve our understanding of parasympathetic reactivation after exercise and the prognostic significance of heart rate recovery.     

Influence of Cheyne-Stokes respiration on ventricular response to atrial fibrillation in heart failure.

In subjects with sinus rhythm, respiration has a profound effect on heart rate variability (HRV) at high frequencies (HF). Because this HF respiratory arrhythmia is lost in atrial fibrillation (AF), it has been assumed that respiration does not influence the ventricular response. However, previous investigations have not considered the possibility that respiration might influence HRV at lower frequencies. We hypothesized that Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) would entrain HRV at very low frequency (VLF) in AF by modulating atrioventricular (AV) nodal refractory period and concealed conduction. Power spectral analysis of R-wave-to-R-wave (R-R) intervals and respiration during sleep were performed in 13 subjects with AF and CSR-CSA. As anticipated, no modulation of HRV was detected at HF during regular breathing. In contrast, VLF HRV was entrained by CSR-CSA [coherence between respiration and HRV of 0.69 (SD 0.22) at VLF during CSR-CSA vs. 0.20 (SD 0.19) at HF during regular breathing, P < 0.001]. Comparison of R-R intervals during CSR-CSA demonstrated a shorter AV node refractory period during hyperpnea than apnea [minimum R-R of 684 (SD 126) vs. 735 ms (SD 147), P < 0.001] and a lesser degree of concealed conduction [scatter of 178 (SD 56) vs. 246 ms (SD 72), P = 0.001]. We conclude that CSR-CSA entrains the ventricular response to AF, even in the absence of HF respiratory arrhythmia, by inducing rhythmic oscillations in AV node refractoriness and the degree of concealed conduction that may be a function of autonomic modulation of the AV node.     

Autonomic nervous system and blood pressure regulation in RGS2-deficient mice

Regulator of G protein signaling (RGS2) deletion in mice prolongs signaling by G protein-coupled vasoconstrictor receptors and increases blood pressure. However, the exact mechanism of the increase in blood pressure is unknown. To address this question we tested autonomic nervous system function and blood pressure regulation in RGS2-deficient mice (RGS2-/-). We measured arterial blood pressure and heart rate (HR) with telemetry, computed time and frequency-domain measures for blood pressure and HR variability (HRV) as well as baroreflex sensitivity [BRS-low frequency (LF)], and assessed environmental stress sensitivity. Mean arterial blood pressure (MAP) was approximately 10 mmHg higher in RGS2-/-compared with RGS2+/+mice, while HR was not different between the groups, indicating a resetting of the baroreceptor reflex. Atropine increased MAP more in RGS2-/-than in RGS2+/+mice while HR responses were not different. Urinary norepinephrine excretion was higher in RGS2-/-than in RGS2+/+mice. The blood pressure decrease following prazosin was more pronounced in RGS2-/-mice than in RGS2+/+mice. The LF and high-frequency (HF) power of HRV were reduced in RGS2-/-compared with controls while BRS-LF and SBP-LF were not different. Atropine and atropine+metoprolol markedly reduced the HRV parameters in the time (RMSSD) and frequency domain (LF, HF, LF/HF) in both strains. Environmental stress sensitivity was increased in RGS2-/-mice compared with controls. We conclude that the increase in blood pressure in RGS2-/-mice is not solely explained by peripheral vascular mechanisms. A central nervous system mechanism might be implicated by an increased sympathetic tone. This state of affairs could lead to a baroreceptor-HR reflex resetting, while BRS remains unimpaired.     

Abnormal heart rate regulation in murine hearts with familial hypertrophic cardiomyopathy-related cardiac troponin T mutations

Mutations in cardiac troponin T (cTnT), Δ160E and R92Q, have been linked to familial hypertrophic cardiomyopathy (FHC), and some studies have indicated that these mutations can lead to a high incidence of sudden cardiac death in the relative absence of significant ventricular hypertrophy. Alterations in autonomic function have been documented in patients with hypertrophic cardiomyopathy. We hypothesize that alterations in autonomic function may contribute to mutation-specific clinical phenotypes in cTnT-related FHC. Heart rate (HR) variability (HRV) has been used to assess autonomic function from an electrocardiograph. Nontransgenic, Δ160E, or R92Q mice were implanted with radiofrequency transmitters to obtain continuous electrocardiograph recordings during 24-h baseline and 30-min recordings after β-adrenergic receptor drug injections. Although Δ160E mice did not differ from nontransgenic mice for any 24-h HRV measurements, R92Q mice had impaired HR regulation, as measured by a decrease in the SD of the R-R interval, a decrease in the low frequency-to-high frequency ratio, a decrease in normalized low frequency, and an increase in normalized high frequency. β-Adrenergic receptor density measurements and HRV analysis after drug injections did not reveal any significant differences for Δ160E or R92Q mice versus nontransgenic mice. Arrhythmia analysis revealed both an increased incidence of heart block in R92Q mice at baseline and frequency of premature ventricular contractions after isoproterenol injections in Δ160E and R92Q mice. In addition, Δ160E and R92Q mice exhibited a prolonged P duration after drug injections. Therefore, between two independent and clinically severe cTnT mutations within the same functional domain, only R92Q mice exhibited altered autonomic function, whereas both mutations demonstrated abnormalities in conduction and ventricular ectopy.     

Longitudinal studies on the effect of hypertension on circadian hemodynamic and autonomic rhythms in telemetered rats

This study dealt with the long-term effects of hypertension on circadian rhythms of hemodynamic and cardiovascular autonomic functions in radiotelemetered rats. Blood pressure (BP), heart rate (HR), spontaneous locomotor activity, and respiration.were monitored in spontaneously hypertensive rats (SHRs), a model of human hypertension, from 14 to 27 weeks of age and in Wistar-Kyoto rats (WKY) as controls. Cardiovascular autonomic changes were determined by time-domain analysis of the variability of BP (standard deviation of mean arterial pressure, SDMAP) and HR (standard deviation of R-R intervals, SDRR, and the root mean square of successive differences in R-R intervals, rMSSD). Compared with WKY rats, the 24-hr MAP and SDMAP were higher at week 14 in SHRs and showed stepwise increases over the study duration, suggesting progressive increases in vasomotor sympathetic activity in hypertensive rats. Also, higher SDRR, rMSSD, and activity and lower HR and respiration were demonstrated in SHRs. Normal circadian rhythms (higher dark-time values) of MAP, HR, SDMAP, and SDRR were evident in WKY rats at week 20 and continued thereafter. Compared with WKY rats, the circadian BP and HR patterns were abolished and inverted, respectively, in SHRs. Lower dark-time, compared with light-time, SDMAP values were observed in SHRs that were associated with temporal increases in HR variability indices. These findings demonstrate that hypertension elicits significant alterations in circadian autonomic and hemodynamic profiles. Further, the steady increases in BP, average level and oscillations, in SHRs may explain the reported progressive age-related vascular and cardiac hypertrophy in these rats.     

Vagal tone dominates autonomic control of mouse heart rate at thermoneutrality

It is generally accepted that cardiac sympathetic tone dominates the control of heart rate (HR) in mice. However, we have recently challenged this notion given that HR in the mouse is responsive to ambient temperature (T(a)) and that the housing T(a) is typically 21-23 degrees C, well below the thermoneutral zone ( approximately 30 degrees C) of this species. To specifically test the hypothesis that cardiac sympathetic tone is the primary mediator of HR control in the mouse, we first examined the metabolic and cardiovascular responses to rapid changes in T(a) to demonstrate the sensitivity of the mouse cardiovascular system to T(a). We then determined HR in 1) mice deficient in cardiac sympathetic tone ("beta-less" mice), 2) mice deficient in cardiac vagal tone [muscarinic M(2) receptor (M(2)R(-/-)) mice], and 3) littermate controls. At a T(a) of 30 degrees C, the HR of beta-less mice was identical to that of wild-type mice (351 +/- 11 and 363 +/- 10 beats/min, respectively). However, the HR of M(2)R(-/-) mice was significantly greater (416 +/- 7 beats/min), demonstrating that vagal tone predominates over HR control at this T(a). When these mice were calorically restricted to 70% of normal intake, HR fell equally in wild-type, beta-less, and M(2)R(-/-) mice (DeltaHR = 73 +/- 9, 76 +/- 3, and 73 +/- 7 beats/min, respectively), suggesting that the fall in intrinsic HR governs bradycardia of calorically restricted mice. Only when the T(a) was relatively cool, at 23 degrees C, did beta-less mice exhibit a HR (442 +/- 14 beats/min) that was different from that of littermate controls (604 +/- 10 beats/min) and M(2)R(-/-) mice (602 +/- 5 beats/min). These experiments conclusively demonstrate that in the absence of cold stress, regulation of vagal tone and modulation of intrinsic rate are important determinants of HR control in the mouse.     

Inhibition of heart rate variability during sleep in humans by 6700 K pre-sleep light exposure

Two different spectral analyses of heart rate (HR) variability (HRV) were performed on seven young male subjects to evaluate the effects of different color temperatures of light exposure (6700 K, 5000 K, 3000 K) before sleep on cardiac vagal activity. In investigating HRV, we used an ordinary fast Fourier transform (FFT) and coarse graining spectral analysis (CGSA), which selectively extracts random fractal components from a given time series. The results showed that suppressions of HR during sleep after 6700 K light exposure were more inhibited than the other two lighting conditions. Increases in high-frequency (HF) components of HRV during sleep were also inhibited by 6700 K pre-sleep lighting. These results indicate that pre-sleep exposure to light of a higher color temperature may inhibit the enhancement of cardiac vagal activity during sleep. Moreover, significant HF alterations were shown in fractal-free HF (not in ordinary HF) components by CGSA. Because the HF component originates from respiratory sinus arrhythmia with periodical fluctuations, CGSA may be an appropriate approach for HRV evaluation during sleep.     

迷走神经和交感神经系统不同活动状态对心率变异性的影响

实验在氯醛糖加氨基甲酸乙酯麻醉的新西兰兔上进行。记录血压、心率、心电图并对心电Ｒ－Ｒ间期（ＲＲＩ）作功率谱密度（ＰＳＤ）分析。以单调性电刺激和低频率的波动性电刺激分别刺激减压神经、疑核和右侧迷走神经外周端,观察到低频率的波动性刺激对增加ＰＳＤ中低频成分（ＬＦ）的作用比单调性电刺激更大（Ｐ〈０．０５）。注射新福林仅在头一个２５６个心动周期时间内引起总变异性（ＴＶ）、ＬＦ、ＰＳＤ中高频成分（ＨＦ）。Ｌ     

Poincaré plot interpretation using a physiological model of HRV based on a network of oscillators

In this paper, we develop a physiological oscillator model of which the output mimics the shape of the R-R interval Poincaré plot. To validate the model, simulations of various nervous conditions are compared with heart rate variability (HRV) data obtained from subjects under each prescribed condition. For a variety of sympathovagal balances, our model generates Poincaré plots that undergo alterations strongly resembling those of actual R-R intervals. By exploiting the oscillator basis of our model, we detail the way that low- and high-frequency modulation of the sinus node translates into R-R interval Poincaré plot shape by way of simulations and analytic results. With the use of our model, we establish that the length and width of a Poincaré plot are a weighted combination of low- and high-frequency power. This provides a theoretical link between frequency-domain spectral analysis techniques and time-domain Poincaré plot analysis. We ascertain the degree to which these principles apply to real R-R intervals by testing the mathematical relationships on a set of data and establish that the principles are clearly evident in actual HRV records.     

Effect of dietary omega-3 fatty acids on the heart rate and the heart rate variability responses to myocardial ischemia or submaximal exercise

The consumption of omega-3 polyunsaturated fatty acids (n-3 PUFAs) has been reported to decrease resting heart rate (HR) and increase heart rate variability (HRV). However, the effects of n-3 PUFAs on these variables in response to a physiological stress (e.g., exercise or acute myocardial ischemia), particularly in postmyocardial infarction (MI) patients, are unknown. Therefore, HR and HRV (high frequency and total R-R interval variability) were evaluated at rest, during submaximal exercise, and during a 2-min coronary artery occlusion at rest and before and 3 mo after n-3 PUFA treatment in dogs with healed MI (n = 59). The dogs were randomly assigned to either placebo (1 g/day corn oil, n = 19) or n-3 PUFA supplement (docosahexaenoic acid + eicosapentaenoic acid ethyl esters; 1 g/day, n = 6; 2 g/day, n = 12; or 4 g/day, n = 22) groups. The treatment elicited significant (P < 0.01) dose-dependent increases in right atrial n-3 PUFA levels but dose-independent reductions in resting HR and increases in resting HRV. In contrast, n-3 PUFAs did not attenuate the large changes in HR or HRV induced by either the coronary occlusion or submaximal exercise. These data demonstrate that dietary n-3 PUFA decreased resting (i.e., preexercise or preocclusion) HR and increased resting HRV but did not alter the cardiac response to physiologic challenges.     

Circadian rhythm of airways caliber and its autonomic modulation

ABSTRACT

The autonomic nervous system (ANS) is one of the effector pathways for circadian variation of many physiological parameters. Autonomic tone and airways caliber have been reported to exhibit circadian variation in separate studies. A simultaneous investigation of heart rate variability (HRV) and airway caliber might ascertain how airway caliber is modulated by autonomic tone. This study was planned to identify the variations in airway caliber and autonomic function tone during a 24-hour span. A total of 56 healthy male subjects with almost similar daily routines were studied. Time domain, frequency domain and nonlinear analysis of R-R interval from 5 min electrocardiogram (ECG) was done seven times during the daytime wake span at 3-hour intervals starting at 05:00 h in the morning until 23:00 h in the night. Simultaneously peak expiratory flow rate (PEFR) was determined using a mini Wright’s peak flow meter. Rhythmometric analysis was done for PEFR and HRV parameters. Significant circadian variation in low frequency (LF) and high frequency (HF) variance was identified in this group of healthy subjects. The circadian rhythm of LF variance was characterized by a gradual increase and corresponding reciprocal change in HF variance from morning until night. The LF/HF ratio and SD2/SD1 ratio reflecting sympatho-vagal balance showed low to high values from morning to evening. The acrophase of the PEFR temporal pattern is similar to that of LF power and almost opposite in phase to that of HF power. PEFR is positively correlated with LF power. The circadian rhythm of airway caliber co-varies with cardiac autonomic tone. It appears that the temporal pattern of cardiac autonomic tone precedes in time that of airways caliber, thereby suggesting the latter operates under the modulatory effect of the 24-hour pattern in sympatho-vagal balance.     

The genetic contribution to heart rate and heart rate variability in quiescent mice

Recent studies have suggested a genetic component to heart rate (HR) and HR variability (HRV). However, a systematic examination of the genetic contribution to the variation in HR and HRV has not been performed. This study investigated the genetic contribution to HR and HRV using a wide range of inbred and recombinant inbred (RI) mouse strains. Electrocardiogram data were recorded from 30 strains of inbred mice and 29 RI strains. Significant differences in mean HR and total power (TP) HRV were identified between inbred strains and RI strains. Multiple significant differences within the strain sets in mean low-frequency (LF) and high-frequency (HF) power were also found. No statistically significant concordance was found between strain distribution patterns for HR and HRV phenotypes. Genomewide interval mapping identified a significant quantitative trait locus (QTL) for HR [LOD (likelihood of the odds) score = 3.763] on chromosome 6 [peak at 53.69 megabases (Mb); designated HR 1 (Hr1)]. Suggestive QTLs for TP were found on chromosomes 2, 4, 5, 6, and 14. A suggestive QTL for LF was found on chromosome 16; for HF, we found one significant QTL on chromosome 5 (LOD score = 3.107) [peak at 53.56 Mb; designated HRV-high-frequency 1 (Hrvhf1)] and three suggestive QTLs on chromosomes 2, 11 and 15. In conclusion, the results demonstrate a strong genetic component in the regulation of resting HR and HRV evidenced by the significant differences between strains. A lack of correlation between HR and HRV phenotypes in some inbred strains suggests that different sets of genes control the phenotypes. Furthermore, QTLs were found that will provide important insight to the genetic regulation of HR and HRV at rest.     

Saturation of high-frequency oscillations of R-R intervals in healthy subjects and patients after acute myocardial infarction during ambulatory conditions

This study was designed to assess the relationship between R-R interval length and heart rate (HR) variability in healthy subjects and patients after an acute myocardial infarction (AMI). Twenty-four-hour ambulatory ECG recordings were obtained for 76 healthy subjects and 82 post-AMI patients. The high-frequency (HF, 0.15-0.4 Hz) spectral power of R-R intervals was analyzed in 5-min sequences over 24 h and plotted as a function of the corresponding mean R-R interval length. Quadratic regression model was used to study the relationship between R-R interval length and HF power. If a distinct deflection point (R-R0) occurred in the quadratic regression (r >0.50) model before maximum R-R interval, indicating the plateau of HF power, the relationship between R-R interval and HF power was defined as saturated. Otherwise, the relationship was defined as linear (r >0.50) or low correlated (r >0.50). The relationship was saturated in 35, linear in 38, and low correlated in 3 healthy subjects. In post-AMI patients, the relationship was saturated in 9 subjects, linear in 44 subjects, and low correlated in 29 patients. The HF power analyzed from the 24-h period did not differ between the saturated and linear groups, but when analyzed from the linear portion only, HF spectral power was smaller in the linear than the saturated group both among healthy subjects (P <0.05) and post-AMI patients (P <0.05). Saturation of the HF oscillations of R-R intervals is a common phenomenon in healthy subjects and also present in post-AMI patients during ambulatory conditions. This saturation effect may bias the quantification of cardiac vagal function when HR variability is analyzed from Holter recordings.     

Changes in R-R and Q-T intervals following cardiac vagotomy in neonatal swine

Asymmetric innervation of the myocardium, especially a predominance of sympathetic innervation, may establish conditions whereby electrical instability could result. Using a swine animal model, we studied the effect of right cardiac vagal denervation on the variability of R-R and Q-T intervals. Newborn pigs were assigned randomly to two groups: sham-operated controls (C), or denervation of the right cardiac vagus nerve (RCVX). EKGs were recorded weekly until the two groups exhibited significant heart rate differences. Analysis of the EKG included measurements of R-R and Q-T intervals and corrected Q-T intervals (QTc). Poincaré plots were used to display age-related differences in R-R and Q-T intervals. For RCVX animals, decreased QTc and R-R intervals were noted at 6 and 7 weeks after denervation, respectively. Unexpectedly, one RCVX animal exhibited marked sudden pauses in sinus rhythm. These data indicated that reduced vagal cardiac modulation during development might alter cardiac electrical stability in conscious swine.