Heart rate variability and electrocardiogram waveform as predictors of morbidity during hypothermia and rewarming in rats

This study examined electrocardiogram (ECG) waveform, heart rate (HR), mean blood pressure (BP), and HR variability as potential autonomic signatures of hypothermia and rewarming. Adult male Sprague-Dawley rats had telemetry transmitters surgically implanted, and 2 weeks were allowed for recovery prior to induction of hypothermia. Rats were lightly anesthetized (sodium pentobarbital, 35 mg/kg i.p.) and placed in a coil of copper tubing through which temperature-controlled water was circulated. Animals were cooled to a core temperature (Tc) of 20 degrees C, maintained there for 30 min, and then rewarmed. Data (Tc, BP, HR from ECG, and 10-s strips of ECG waveforms) were collected every 5 min throughout hypothermia and rewarming. Both HR and BP declined after initial increases with the drop in HR starting at a higher Tc than the drop in BP (29.6 +/- 2.4 degrees C vs. 27.1 +/- 3.3 degrees C, p < 0.05). Animals that were not successfully rewarmed exhibited a significant (p < 0.05) increase in the normalized standard deviation of interbeat intervals (IBI) throughout cooling compared with animals that were successfully rewarmed. The T wave of the ECG increased in amplitude and area with decreasing Tc. T-wave amplitude and IBI variability show potential as predictors of survival in hypothermic victims.     

Comparison of three methods for beat-to-beat-interval extraction from continuous blood pressure and electrocardiogram with respect to heart rate variability analysis.

In recent years the analysis of heart rate variability (HRV) has become a suitable method for characterizing autonomous cardiovascular regulation. The aim of this study was to investigate the differences in HRV estimated from continuous blood pressure (BP) measurement by different methods in comparison to electrocardiogram (ECG) signals. The beat-to-beat intervals (BBI) were simultaneously extracted from the ECG and blood pressure of 9 cardiac patients (10 min, Colin system, 1000-Hz sampling frequency). For both data types, slope, peak, and correlation detection algorithms were applied. The short-term variability was calculated using concurrent 10-min BP and ECG segments. The root mean square errors in comparison to ECG slope detection were: 1.74 ms for ECG correlation detection; 5.42 ms for ECG peak detection; 5.45 ms for BP slope detection; 5.75 ms for BP correlation detection; and 11.96 ms for BP peak detection. Our results show that the variability obtained with ECG is the most reliable. Moreover, slope detection is superior to peak detection and slightly superior to correlation detection. In particular, for ECG signals with higher frequency characteristics, peak detection often exhibits more artificial variability. Besides measurement noise, respiratory modulation and pulse transit time play an important role in determining BBI. The slope detection method applied to ECG should be preferred, because it is more robust as regards morphological changes in the signals, as well as physiological properties. As the ECG is not recorded in most animal studies, distal pulse wave measurement in combination with correlation or slope detection may be considered an acceptable alternative.     

Diagnostic screening of the human myocardium during the bicycle exercise test

The diagnostic and prognostic potentialities of Kardio-Vizor-06 (KV) in early detection of deviations in the myocardial electrophysiological parameters were assessed using the standard functional bicycle stress exercise test. Ten apparently healthy subjects from different age groups were examined. The data obtained with KV (baseline, loading, and in the recovery period) were compared with the results of the standard ECG (12 leads) and blood pressure (BP) methods. Data agreement was observed in 90% of cases; KV underestimated the test tolerance in 10% of cases. Detailed examination of ECG verified the presence of incipient alterations in the myocardium. Thus, unlike other methods, this technology provides unique information and predicts transient functional disorders that are precursors of pathology. The high noise resistance of the automated analysis of the dispersion of the ECG signal makes the device applicable directly during functional loading tests.     

Phase and frequency locking of 0.1-Hz oscillations in heart rate and baroreflex control of blood pressure by breathing of linearly varying frequency as determined in healthy subjects

Functional interaction was studied between the subsystems that ensure autonomic control of the heart rate (HR) and blood pressure (BP) and give rise to 0.1-Hz oscillations in R-R intervals (RRI) and photoplethysmogram (PPG). Twenty-five recordings were obtained from 18- to 32-year-old healthy persons (six women and nineteen men). The RRI and PPG were recorded simultaneously while the respiration rate of a subject in the sitting position increased linearly from 0.05 Hz to 0.25 Hz within 25 min. Phase and frequency locking of 0.1-Hz oscillations by breathing proved to be possible in both RRI and PPG. The intervals of phase and frequency locking of oscillations by respiration differed in duration and relative position. These distinctions suggest that the mechanisms of autonomic 0.1-Hz control of HR and BP are functionally independent.     

Modeling the circadian variability of ambulatorily monitored blood pressure by multiple-component analysis

The use of a set of new end points derived from ambulatory blood pressure monitoring (ABPM), in addition to the blood pressure (BP) values themselves, has been advocated to improve the sensitivity and specificity in diagnosing hypertension and to evaluate a person's response to treatment. An adequate estimation of rhythmic parameters depends, however, on the ability to describe properly the circadian pattern of BP variability. The purpose of this study was to identify a simple model that could characterize sufficiently well the circadian pattern of BP in normotensive healthy volunteers sampled by ambulatory monitoring. We studied 278 clinically healthy Spanish adults (184 men), 22.7±3.3 yr of age, without medical history of hypertension and mean BP from ambulatory profiles always below 135/85 mmHg for systolic/diastolic BP, who underwent sequential ABPM providing a total of 1115 series of BPs and heart rates (HRs), sampled on each occasion at 0.5h intervals for 48 h. Subjects were assessed while adhering to their usual diurnal activity and nocturnal sleep routine, without restrictions but avoiding the use of medication. The circadian rhythm in BP and HR for each subject was established by multiple-component analysis. A statistically significant 24h component is documented for 97% of the BP profiles, with a significant second (12h) harmonic documented in 65% of the profiles. Other ultradian harmonic components were significant in less than 20% of the profiles. A statistically significant increase in the coefficient of determination (percent of overall variability explained by the function fitted to the data) was only obtained after including the periods of 24 and 12 h for BP, and periods of 24, 12, and 6 h for HR in the model components. Although other ultradian components can be demonstrated as statistically significant in a small percent of subjects, a rather simple model including only the two first harmonics of the 24h period describes sufficiently well, at the specified sampling rate, the circadian pattern of BP in normotensive subjects. Departure from this model could characterize overt pathology, as recently demonstrated in the diagnosis of preeclampsia.     

Modeling the circadian variability of ambulatorily monitored blood pressure by multiple-component analysis

The use of a set of new end points derived from ambulatory blood pressure monitoring (ABPM), in addition to the blood pressure (BP) values themselves, has been advocated to improve the sensitivity and specificity in diagnosing hypertension and to evaluate a person's response to treatment. An adequate estimation of rhythmic parameters depends, however, on the ability to describe properly the circadian pattern of BP variability. The purpose of this study was to identify a simple model that could characterize sufficiently well the circadian pattern of BP in normotensive healthy volunteers sampled by ambulatory monitoring. We studied 278 clinically healthy Spanish adults (184 men), 22.7±3.3 yr of age, without medical history of hypertension and mean BP from ambulatory profiles always below 135/85 mmHg for systolic/diastolic BP, who underwent sequential ABPM providing a total of 1115 series of BPs and heart rates (HRs), sampled on each occasion at 0.5h intervals for 48 h. Subjects were assessed while adhering to their usual diurnal activity and nocturnal sleep routine, without restrictions but avoiding the use of medication. The circadian rhythm in BP and HR for each subject was established by multiple-component analysis. A statistically significant 24h component is documented for 97% of the BP profiles, with a significant second (12h) harmonic documented in 65% of the profiles. Other ultradian harmonic components were significant in less than 20% of the profiles. A statistically significant increase in the coefficient of determination (percent of overall variability explained by the function fitted to the data) was only obtained after including the periods of 24 and 12 h for BP, and periods of 24, 12, and 6 h for HR in the model components. Although other ultradian components can be demonstrated as statistically significant in a small percent of subjects, a rather simple model including only the two first harmonics of the 24h period describes sufficiently well, at the specified sampling rate, the circadian pattern of BP in normotensive subjects. Departure from this model could characterize overt pathology, as recently demonstrated in the diagnosis of preeclampsia.     

Postural-induced phase shift of respiratory sinus arrhythmia and blood pressure variations: insight from respiratory-phase domain analysis

The purpose of this study is to evaluate the multiple effects of respiration on cardiovascular variability in different postures, by analyzing respiratory sinus arrhythmia (RSA) and respiratory-related blood pressure (BP) variations for systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) in the respiratory-phase domain. The measurements were conducted for 420 s on healthy humans in the sitting and standing positions, while the subjects were continuously monitored for heart rate and BP variability and instantaneous lung volume. The waveforms of RSA and respiratory-related BP variations were extracted as a function of the respiratory phase. In the standing position, the waveforms of the BP variations for SBP, DBP, and PP show their maxima at around the end of expiration (pi rad) and the minima at around the end of inspiration (2 pi rad), while the waveform of RSA is delayed by approximately 0.35 pi rad compared with the BP waveforms. On the other hand, in the sitting position, the phase of the DBP waveform (1.69 pi rad) greatly and significantly (P < 0.01) differs from that in the standing position (1.20 pi rad). Also, the phase of PP is delayed and that of RSA is advanced in the sitting position (P < 0.01). In particular, the phase shift of the DBP waveform is sufficiently large to alter whole hemodynamic fluctuations, affecting the amplitudes of SBP and PP variations. We conclude that the postural change associated with an altered autonomic balance affects not only the amplitude of RSA, but also the phases of RSA and BP variations in a complicated manner, and the respiratory-phase domain analysis used in this study is useful for elucidating the dynamic mechanisms of RSA.     

Effects of pericardial constraint and ventricular interaction on left ventricular hemodynamics in the unloaded heart

Pericardial constraint and ventricular interaction influence left ventricular (LV) performance when preload is high. However, it is unclear if these constraining forces modulate LV filling when the heart is unloaded, such as during upright posture, in humans. Fifty healthy individuals underwent right heart catheterization to measure pulmonary capillary wedge (PCWP) and right atrial pressure (RAP). To evaluate the effects of pericardial constraint on hemodynamics, transmural filling pressure (LVTMP) was defined as PCWP-RAP. Beat-to-beat blood pressure (BP) waveforms were recorded, and stroke volume (SV) was derived from the Modelflow method. After measurements at -30 mmHg lower body negative pressure (LBNP), which approximates the upright position, LBNP was released, and beat-to-beat measurements were performed for 15 heartbeats. At -30 mmHg LBNP, RAP and PCWP were significantly decreased. During the first six beats of LBNP release, heart rate (HR) was unchanged, while BP increased from the fourth beat. RAP increased faster than PCWP resulting in an acute decrease in LVTMP from the fourth beat. A corresponding drop in SV by 3% was observed with no change in pulse pressure. From the 7th to 15th beats, LVTMP and SV increased steadily, followed by a decreased HR due to the baroreflex. A decreased TMP, but not PCWP, caused a transient drop in SV with no changes in HR or pulse pressure during LBNP release. These results suggest that the pericardium constrains LV filling during LBNP release, enough to cause a small but significant drop of SV, even at low cardiac filling pressure in healthy humans.     

The blood pressure and heart rate chronome of centenarians.

Rhythm characteristics of blood pressure (BP) and heart rate (Hr) of 11 healthy centenarians and 66 medical students are described. Each subject ambulatorily monitored measured BP and HR around the clock at 15-min intervals for 48 hours. Least-squares spectra were obtained by the fit of cosine curves (cosinor) and compared between the two populations. Confounding by geographic differences seems to be ruled out by comparisons with results from international data bases. A shift in prominence from the circadian domain to higher frequency harmonics was found for the BP but not for the HR of centenarians. In clinically mostly healthy centenarians, markers of primary aging may consist of a relatively low circadian BP and HR amplitude and a tendency toward internal and external desynchronization. Whether these chronobiologic changes with age are desirable, indifferent or undesirable can now be elucidated by outcome studies, in the light of the reference standards provided herein.     

The use of spiroarteriocardiorhythmography as a functional test for estimating the state of the cardiorespiratory system in adults and children

The heart rate, peripheral arterial blood pressure (BP), and respiration parameters were simultaneously recorded in adult subjects and young schoolchildren in two modes of testing: using a mask with airflow sensors that did not restrict air inflow but increased the pulmonary dead space and without the mask. It was demonstrated that wearing the mask was a functional test for the state of the cardiorespiratory system in both age groups; however, the responses of the children’s and adults’ bodies differed from each other, probably, because of the functional immaturity of the sympathetic component of the autonomic control. In adults, the parameters of the cardiovascular system did not change, except that the heart rate variability spectrum was redistributed toward an enhancement of the high-frequency component. In children, testing with the mask on decreased the systolic BP; increased the heart rate; and, as evidenced by the spectral characteristics of BP variability, activated the sympathetic nervous system.     

下体负压对家兔血液动力学的影响

观察了家兔在-20、-40、-60mmHg下体负压下心输出量、心搏量、心率、血压以及心电图、脑电图、视网膜电图的变化。实验结果表明:心搏量与心输出量明显减少,在-60mmHg下作用10分钟两者可下降到负压前对照值的15％。心率大多数加快,以代偿心输出量的下降。如出现持续性心率过缓和心律不齐,标志代偿失调。收缩压、舒张压、平均动脉压、脉压均呈规律性下降。根据血压反应可将动物分为耐力良好、尚好、较差三种类型。心电图变化主要表现为冠脉供血不足,心肌缺氧特征,并伴有高尖状P波。脑电图出现缺氧性慢波、波幅降低。视网膜电图的b波波幅逐渐下降,持续期缩短,80％以上有b负波,这些变化可能与脑部及视网膜供血不足有关。     

Hypertension Increases With Aging and Obesity in Chimpanzees (Pan troglodytes)

Cardiovascular disease is a primary cause of morbidity and mortality in captive chimpanzees. Four years of blood pressure (BP) data were analyzed from a captive former laboratory population of 201 healthy adult chimpanzees with assessment of age and obesity on elevated BP. Five different measures of obesity were compared: abdominal girth, basal metabolic rate, body‐mass index (BMI), body weight, and surface area. Systolic BP varied by sex. Obesity did not influence male BP. For females, obesity was a significant determinant of BP. The best measure of female obesity was basal metabolic rate and the worst was BMI. Median systolic BP of healthy weight females (<54.5 kg) was significantly lower (128 mmHg) than overweight or obese females (140 mmHg), but both were lower than all males (147 mmHg). For diastolic BP, neither sex nor any of the five obesity measures was significant. But age was highly significant, with geriatric chimpanzees (>30 years) having higher median diastolic BP (74 mmHg) than young adults of 10–29 years of age (65 mmHg). By these criteria, 80% of this population is normotensive, 7% prehypertensive, and 13% hypertensive. In summary, systolic BP intervals required adjustment for obesity among females but not males. Diastolic BP required adjustment for advanced age (≥30 years). Use of these reference intervals can facilitate timely clinical care of captive chimpanzees. Zoo Biol. 32:79‐87, 2013. © 2012 Wiley Periodicals, Inc.     

A modified Zeeman model for producing HRV signals and its application to ECG signal generation

Developing a mathematical model for the artificial generation of electrocardiogram (ECG) signals is a subject that has been widely investigated. One of the challenges is to generate ECG signals with a wide range of waveforms, power spectra and variations in heart rate variability (HRV)--all of which are important indexes of human heart functions. In this paper we present a comprehensive model for generating such artificial ECG signals. We incorporate into our model the effects of respiratory sinus arrhythmia, Mayer waves and the important very low-frequency component in the power spectrum of HRV. We use a new modified Zeeman model for generating the time series for HRV, and a single cycle of ECG is produced by using a simple neural network. The importance of the work is the model's ability to produce artificial ECG signals that resemble experimental recordings under various physiological conditions. As such the model provides a useful tool to simulate and analyse the main characteristics of ECG, such as its power spectrum and HRV under different conditions. Potential applications of this model include using the generated ECG as a flexible signal source to assess the effectiveness of a diagnostic ECG signal-processing device.     

Effect of static exercise and muscle ischemia on cardiac function as evaluated by the systolic time intervals

To determine the role of muscle chemoreflex in the cardiac response to static exercise the effect of the forearm muscle ischemia on systolic time intervals (STI), heart rate (HR) and blood pressure (BP) recovery following static handgrip was studied in 7 healthy men. During handgrip maintained for 4 min at 30% maximal voluntary contraction HR and BP increased significantly while duration of the pre-ejection period (PEP) and isovolumic contraction time (ICT) were shortened with a significant lowering in the ratio of PEP to the left ventricle ejection time (LVET). Occlusion of the circulation to the forearm muscles for 2 min after cessation of exercise did not prevent a rapid decline of HR or increment in PEP, ICT and PEP-to-LVET ratio while BP remained elevated for as long as blood flow to muscles was restricted. The study failed to demonstrate an appreciable effect of muscle chemoreflex on HR or myocardial contractility, suggesting that input from muscle afferents activated by metabolic stimuli induces the pressor response mainly by the peripheral vasoconstriction.     

Circadian Rhythm of Blood Pressure and Heart Rate in Cardiopathic Patients Before and After Heart Transplantation

The aim of this study was to investigate the natural history of the circadian rhythm of blood pressure (BP) and heart rate (HR) in 10 patients with heart failure (class IV of the New York Heart Association), who underwent heart transplantation because of primary congestive cardiomyopathy. The control group was 10 age-matched clinically healthy subjects. The BP and HR monitor-ings were performed before and after transplantation. Preoperatively, analysis of variance and cosinor methods validated the occurrence of a statistically significant BP and HR circadian rhythm in cardiopathic patients. Over the 4 days after surgery, both the cosinor method and serial section analysis were unable to validate a 24-h periodicity for BP and HR in patients with heart transplants. Six months after surgery, the BP and HR circadian rhythm was not detected as well. One year after transplantation. the BP and HR circadian rhythm was statistically validated. The recovery of the BP and HR circadian rhythm 1 year after heart transplantation can be regarded as a clinical sign of a reacquired susceptibility to neurovegetative chronoregulation.     

Comparative Evaluation of Heart Rate Variability Based on the Data of ECG and Blood Pressure Measurements

The development of new approaches to the assessment of heart rate variability (HRV) is an important problem, since HRV reflects the functioning of cardiovascular control and is affected by various diseases. The purpose of this study was to evaluate the informative value of statistical and spectral HRV parameters calculated from pulse interval (PI) data of blood pressure as compared with those calculated from RR-interval data of electrocardiograms (ECG). We recorded ECG in conscious rats using skin adhesive electrodes simultaneously with blood pressure signal obtained through a catheter in the femoral artery. It has been found that the PI sequence can be used to calculate the statistical HRV indices that describe the HRV at time intervals about 1 min or longer, but statistical indices of the PI and RR intervals may differ in the analysis of beat-tobeat variations. The power spectra of the RR intervals and PI coincide in the low-frequency region, including the band of baroreflex cardiac rhythm oscillation. However, they can differ in the high-frequency region (at respiration frequency and above).     

Cardiovascular and norepinephrine responses of men and women to two cold pressor tests.

Two types of cold pressor tests were used to study gender differences in cardiovascular and plasma catecholamine responses. Ten male and ten female, young, healthy Caucasian subjects participated. The tests consisted of (1) 5 degrees C air blown at 3.5-4 m/s onto part of the face for 4 min and (2) the open right hand immersed to the wrist in water at 5 degrees C for 4 min. Heart rate, blood pressure (BP), and venous plasma norepinephrine were collected before, during, and 5 min after the 4 min of cold exposures. Test order was decided by a Latin square design, and the subjects rested in a quiet room for 30 min between the two tests. All parameters demonstrated significant (p less than 0.01) increases from rest during the cold tests. Gender differences were significant (p less than 0.01) in diastolic and systolic BP in each test with the males having a greater response, but gender differences were not found in heart rate or norepinephrine concentration. The study demonstrated that gender differences exist in the blood pressure responses to local cold, but that the mechanisms involved do not include a parallel difference in heart rate or venous plasma norepinephrine concentration.     

Systematic nocturnal atrial demand pacing results in high-output heart failure.

Beat-to-beat parameters of heart rate (HR), intra-arterial blood pressure (BP), central venous pressure, and derived indexes of cardiac output and total peripheral resistance were recorded 18 h/day (from 1800 to 1200 h the following day) in four monkeys (Macaca mulatta) during 20 control days followed by 20 days of atrial demand pacing. The pacing rate was set at approximately 10 beats/min above the fastest hourly average HR recorded during the control period, i.e., sufficient to prevent the normal nocturnal fall in HR. Nocturnal pacing resulted in progressive weekly increases in central venous BP and arterial BP. Analyses of levels and diurnal trends in hemodynamic parameters and cardiac function curves across consecutive 5-day periods of nocturnal pacing revealed a hemodynamic pattern characteristic of high-output heart failure, which progressively increased (week by week) during the early morning hours (0500-0700). Sustained elevated left ventricular work resulting from the prevention of a nocturnal fall in HR may have been responsible for the reduction in cardiac function seen in this experimental model.     

Changes in regional blood volume and blood flow during static handgrip

Increased blood pressure (BP) and heart rate during exercise characterizes the exercise pressor reflex. When evoked by static handgrip, mechanoreceptors and metaboreceptors produce regional changes in blood volume and blood flow, which are incompletely characterized in humans. We studied 16 healthy subjects aged 20-27 yr using segmental impedance plethysmography validated against dye dilution and venous occlusion plethysmography to noninvasively measure changes in regional blood volumes and blood flows. Static handgrip while in supine position was performed for 2 min without postexercise ischemia. Measurements of heart rate and BP variability and coherence analyses were used to examine baroreflex-mediated autonomic effects. During handgrip exercise, systolic BP increased from 120 +/- 10 to 148 +/- 14 mmHg, whereas heart rate increased from 60 +/- 8 to 82 +/- 12 beats/min. Heart rate variability decreased, whereas BP variability increased, and transfer function amplitude was reduced from 18 +/- 2 to 8 +/- 2 ms/mmHg at low frequencies of approximately 0.1 Hz. This was associated with marked reduction of coherence between BP and heart rate (from 0.76 +/- 0.10 to 0.26 +/- 0.05) indicative of uncoupling of heart rate regulation by the baroreflex. Cardiac output increased by approximately 18% with a 4.5% increase in central blood volume and an 8.5% increase in total peripheral resistance, suggesting increased cardiac preload and contractility. Splanchnic blood volume decreased reciprocally with smaller decreases in pelvic and leg volumes, increased splanchnic, pelvic and calf peripheral resistance, and evidence for splanchnic venoconstriction. We conclude that the exercise pressor reflex is associated with reduced baroreflex cardiovagal regulation and driven by increased cardiac output related to enhanced preload, cardiac contractility, and splanchnic blood mobilization.     

Further steps toward a neonatal chronocardiology

The study of 53 series of blood pressures at half-hour intervals from clinically healthy full-term newborns during the first days of life reveals various classifiers correlating with a history of high blood pressure: the circadian amplitude of diastolic blood pressure, the 50% range of systolic blood pressure and the standard deviation of heart rate.