Taina Metsälä

Regulation of heart rate variation by the autonomic nervous system in neonatal lambs

ABSTRACT: We studied the role of the autonomic nervous system in the regulation of heart rate variation (HRV) in 12 chronically instrumented neonatal lambs. HRV was quantified from ECG tracings by computing periodic HRV distributions at frequencies of 0.02-1.00 Hz, using power spectral analysis of heart rate, and also by HRV indices. Heart rate declined more during the 1st than the 2nd mo after birth. Multiple regression analysis showed that the heart rate responses to vagal and to β-adrenergic blockade had an independent negative association both with age and with the initial mean heart rate, whereas the overall HRV response had a positive association with age. Vagal blockade led to a 70-80% decrease in the beat-to-beat HRV in all lambs (p < 0.001). The overall HRV indices decreased by 40-65% in lambs (< 30 d old (p < 0.001) and about 30% in those >30 d old (p < 0.05). In the power spectrum the greatest decrease was seen in the high-frequency components of HRV. β-Blockade led to a decrease of about 50% in all HRV (p < 0.001) in the younger lambs, without frequency selection. In the older lambs, it had no effect on the beat-to-beat HRV, but the overall HRV (coefficient of variance) decreased maximally by 40% (p < 0.01), with a significant reduction in the low-frequency components of HRV. These results suggest that in the regulation of HRV after birth dual control via the autonomic nervous system is most important. In the older lambs, developmental changes result in precise regulation of the fast heart rate fluctuations mainly by the vagal division, whereas the slow fluctuations are partially regulated by the vagal and β- adrenergic divisions.

Periodic spectral components of fetal heart rate variability reflect the changes in cord arterial base deficit values: a preliminary report

Fetal distress changes the function of the autonomic nervous system. These changes are reflected in the fetal heart rate and can be quantified with power spectrum analysis of heart rate variability. The purpose of this study was to find out whether spectral components of fetal heart rate variability (FHRV) during labor are associated with fetal cord arterial base deficit values at birth. The association between FHRV and umbilical cord arterial base deficit was studied in 14 singleton fetuses with normal pregnancy at 35-40 weeks of gestation. Fetal ECG was recorded by scalp-electrode using a STAN Fetal ECG monitor (Cinventa Ab, Mölndal, Sweden). FHRV was quantified by computing Fast-Fourier-transformed heart rate (HR) spectra at three frequency bands: low-frequency (LF) 0.03-0.07 Hz, mid-frequency (MF) 0.07-0.13 Hz and high-frequency (HF) 0.13-1.0 Hz. We found that total FHRV and MF FHRV were lower in fetuses with cord arterial base deficit 8 to 12 mmol/L in comparison to the fetuses with normal cord arterial base deficit value (P=0.02 and P=0.01, respectively). A linear correlation was found between the spectral densities and the cord arterial base deficit values (r=0.4 and r=0.6, respectively). We conclude that the results suggest changes in the autonomic nervous cardiac control in fetuses with cord arterial base deficit between 8 to 12 mmol/L. The clinical applicability of our observations on FHRV in predicting fetal distress remains to be further studied.

Comparison of autonomic withdrawal in men with obstructive sleep apnea syndrome, systemic hypertension, and neither condition

Obstructive sleep apnea syndrome is characterized by obesity, nocturnal breathing abnormalities, arterial hypertension, and an increased number of cardiovascular events. Sympathetic activity is increased during nocturnal apneic episodes, which may mediate the cardiovascular complications of sleep apnea. We studied 15 male subjects with obstructive sleep apnea syndrome and associated hypertension, 54 subjects with mild to moderate essential hypertension, and 25 healthy normotensive men. Cardiovascular autonomic control was assessed using frequency domain measures of heart rate variability (HRV) during a controlled breathing test and during orthostatic maneuver. Compared with normotensive and hypertensive groups, total power and low- and high-frequency components of HRV during controlled breathing were significantly (analysis of variance, p<0.0001) lower in the obstructive sleep apnea syndrome. During the orthostatic maneuver, the change in total power of HRV was different between the 3 groups (analysis of variance, p = 0.004). The total power of HRV tended to increase in the normotensive (4.11+/-12.29 ms2) and in hypertensive (2.31+/-12.65 ms2) groups, but decreased (1.13+/-1.23 ms2) in the hypertensive group with obstructive sleep apnea syndrome. According to multivariate regression analysis, age and sleep apnea were the major independent determinants of HRV. This study found that an abnormal response to autonomic nervous tests characterizes hypertension in overweight subjects with obstructive sleep apnea syndrome. This could be due to autonomic withdrawal or supersaturation of the end-organ receptors by excessive and prolonged sympathetic stimulation. Our results also show the reduced response of orthostatic maneuver and controlled breathing in the hypertensive group compared with the normotensive group.

Beta-adrenergic control and inter-relationships between heart rate and blood pressure in neonatal lambs

Our aim was to develop a signal analysis method for revealing interrelationships between heart rate and blood pressure and for displaying the influence of autonomic nervous control on these signals in a chronic lamb model. A chronically instrumented neonatal lamb model was made to record ECG and direct arterial blood pressure (N=15). Continuous two-minute recordings of blood pressure (BP) and ECG were digitised. The instantaneous heart rate signal (IHR) was derived from the ECG. The IHR and BP signals were bandpass filtered. Autospectra, cross-spectra, coherence spectra and phase spectra for the signals were computed to study the relative magnitudes and inter-relationships of the cardiovascular signals under normal conditions and during beta-adrenergic blockade. It was noted that both in the BP and IHR there were oscillations at the frequency of <0·1 Hz and also at the respiratory rate around 0·6 Hz. Beta-blockade reduced the oscillations of the IHR in <30-day-old lambs. It did not affect the coherence spectra or the phase lag between the signals. During quiet sleep the variability of blood pressure was decreased. In over-30-day-old-lambs the beta-blockade did not affect the variabilities of the cardiovascular parameters. These findings indicate that in neonatal lambs the sympathetic control system is a major regulator of cardiovascular interactions.

Computer analysis of heart rate variation and breathing movements in fetal lambs.

A quantitative method for studying the frequency-specific relationships between heart rate (HR) and fetal breathing movements (FBM) was developed. The reactivity of periodic HR variation in relation to FBM was investigated by means of power spectral analysis. Seven fetal lambs were studied during the third trimester of gestation using a chronic animal model. HR variability increased at the rate of FBM, as shown by an increase of spectral density at >0·35 Hz in the HR autospectrum and in the cross-spectrum of HR and respirogram, as well as by an increase in the shorterm variability index CVS. FBM were associated with the increased HR variation in all but the lowest frequency bands (0·07-1·0 Hz). Although respiratory sinus arrhythmia was found, only 10 per cent of the total HR variability and 25 per cent of the joint-density of HR and respirogram appeared at <0·35 Hz during FBM. The greatest variation in both the HR and respirogram spectra appeared at <0·07 Hz. Although the low-frequency variability of HR and respirogram was simultaneous, it was on the whole not synchronised. The existence of multiple control systems that simultaneosly link the cardiac and respiratory control mechanisms to each other in the fetal lamb is postulated.

Association of abnormal flow velocity waveforms in the uterine artery with frequency-specific fetal heart rate variability

The aim of the study was to determine if abnormal flow velocity waveforms in the uterine artery are associated with altered frequency-specific fetal heart rate variability (HRV). Fetuses in the last third of gestation were studied. In seven fetuses the pulsatility index (PI) of the blood flow velocity waveform in the uterine artery was increased (Group II), and in ten fetuses the PI was normal (Group I). Frequency-specific HRV (0.025-0.07 Hz, 0.07-0.13 Hz, 0.13-1.0 Hz) was quantified by power spectral analysis and correlated with the PI in the uterine artery, umbilical artery and the middle cerebral artery. The slow variability dominated the fetal HRV. There was no difference between the groups in the mean frequency-specific variability. In Group II, an increase of the PI in the umbilical artery and a decrease in the middle cerebral artery correlated with an increase of HRV, the increase being greatest at the lowest frequency band.

Ramipril Enhances Autonomic Control in Essential Hypertension: A Study Employing Spectral Analysis of Heart Rate Variation.

We estimated the effect of an angiotensin-converting enzyme inhibitor, ramipril, on the sympathetic and parasympathetic input to the sinoatrial node of hypertensive patients using spectral and time domain analysis of heart rate variation (HRV). The heart rate of patients with essential hypertension was recorded during spontaneous breathing at rest and during controlled deep breathing. The periodic HRV was quantified at low-frequency (0.025–0.075 Hz), mid-frequency (0.075–0.125 Hz) and high-frequency (0.15–0.40 Hz) bands. Ramipril changed the balance of autonomic nervous system assessed by spectra: the parasympathetic tone increased (p < 0.05) and the sympathetic tone decreased (p < 0.01). There was an inverse correlation between the decrease in diastolic blood pressure and increase in the mid-frequency HRV, which is connoted with resetting of the baroreceptor reflex by ramipril. Thus, ramipril treatment was associated with improved autonomic control of the circulatory system.