Fetal cardiac sympathetic activation is linked with maternal body mass index.

BACKGROUND: Sympathetic over activity has been suggested to impact on the risk of cardiovascular diseases. The origin of abnormalities in the autonomic nervous system is unknown, but it is susceptible to environmental influences during the critical periods of human development. AIMS: To examine the influence of maternal characteristics on fetal cardiac autonomic nervous activation. STUDY DESIGN: Prospective, observational study. SUBJECTS: 41 fetuses from normal pregnancy born after 36 gestational weeks. OUTCOME MEASURES: Maternal characteristics that affect fetal intrauterine well-being intrauterine environmental factors were evaluated, including pre-pregnancy body mass index as well as GHbA1c, blood pressure and 3-day food diaries from each trimester of pregnancy. To assess intrapartum fetal cardiac sympathovagal activation fetal ECG was recorded for 1 h during delivery. Heart rate variability was measured using power spectrum analysis of low-to-high frequency ratio of fetal heart rate variability. RESULTS: Cardiac sympathetic activation measured during delivery was associated with maternal pre-pregnancy body mass index (r=0.33, p=0.03), placental weight (r=0.4, p=0.008) and the immaturity of the fetus (r=-0.3, pb0.05). CONCLUSION: Early intrauterine environmental factors such as maternal pre-pregnancy body mass index are associated with fetal sympathetic activation with a potential for cardiovascular programming.

Inhaled nitric oxide treatment inhibits neuronal injury after meconium aspiration in piglets.

BACKGROUND: Meconium aspiration-induced hypertensive lung injury is frequently associated with neuronal damage. Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension, but its effects on the brain are poorly known. AIMS: The aim of this study was to determine the effects of iNO treatment on the neuronal tissue after meconium aspiration. STUDY DESIGN: 71 anesthetized, catheterized and ventilated newborn piglets were studied for 6 h. Thirty-five piglets were instilled with a bolus of human meconium intratracheally and 36 piglets with saline instillation served as controls. Nineteen meconium piglets and 17 control piglets were continuously treated with 20 ppm of iNO, started at 30 min after the insult. The extent of neuronal injury was analysed histologically, and the levels of brain tissue lipid peroxidation products, reduced glutathione (GSH), myeloperoxidase activity and oxidized DNA were analysed as indicators of oxidative stress. RESULTS: iNO treatment diminished the pulmonary hypertensive response caused by meconium aspiration, but did not change systemic or carotid hemodynamics. NO administration was associated with reduced neuronal injury and diminished amount of oxidized DNA in the hippocampus of the meconium piglets. Further, iNO treatment was associated with decreased level of GSH in the cortex, but no change in lipid peroxidation production or myeloperoxidase activity was detected in any of the studied brain areas. CONCLUSIONS: Our results suggest that iNO treatment may inhibit DNA oxidation and neuronal injury in the hippocampus, associated with newborn meconium aspiration.

Meconium aspiration induces oxidative injury in the hippocampus of newborn piglets.

BACKGROUND: Meconium aspiration-induced hypertensive lung injury has been associated with neuronal damage in the newborn, but the mechanisms of the injury are poorly known. AIMS: The aim of the study was to determine the contribution of oxidative stress to the brain damage after pulmonary meconium contamination. STUDY DESIGN: Sixteen anesthetized and ventilated newborn piglets were studied for 6 h. Eight piglets were instilled with a bolus of human meconium intratracheally and eight piglets with saline instillation served as controls. Brain tissue lipid peroxidation products (TBARS), reduced glutathione (GSH), myeloperoxidase activity and oxidized DNA were analyzed as indicators of oxidative stress. RESULTS: Meconium aspiration did not change the systemic or carotid hemodynamics, but caused a well-established pulmonary hypertensive response. Sustained increase in additional oxygen demand was also observed after meconium insult, but no actual hypoxemia or hypercarbia was evident during the whole study period. Myeloperoxidase activity was elevated in the cerebellum after pulmonary meconium instillation, whereas concentrations of peroxidation products and glutathione were similar in the cortical, cerebellar and hippocampal regions of the two groups. Still, the amount of oxidized DNA was increased in the hippocampus of the meconium-aspirated piglets when compared to controls. CONCLUSIONS: Our data thus suggest that oxidative injury associated with pulmonary, but not systemic, hemodynamic disturbances may contribute to hippocampal damage after meconium aspiration in newborns.

Marked fetal acidosis and specific changes in power spectrum analysis of fetal heart rate variability recorded during the last hour of labour.

OBJECTIVE: To assess whether intrapartum acidosis affects specific components of fetal heart rate variability. DESIGN: Prospective clinical study. SETTING: Twelve Nordic delivery units. SUBJECTS: Fetal heart rate variability was studied in 334 fetuses divided into two groups according to cord pH value: the acidotic group (cord arterial pH < 7.05 at birth, n= 15) and the control group (cord arterial pH > or =7.05 at birth, n= 319). METHODS: In spectral analysis of fetal heart rate variability, frequencies were integrated over the total frequency band (0.04-1.0 Hz), low-frequency band (0.04-0.15 Hz) and high-frequency band (0.15-1.0 Hz). We also calculated the low-to-high frequency ratio. MAIN OUTCOME MEASURES: The spectral bands of fetal heart rate variability were compared between the acidotic and control fetuses. RESULTS: We found that during the last hour of monitoring, baseline fetal heart rate gradually decreased, whereas total, low-frequency and high-frequency fetal heart rate variability initially increased but then, near the delivery, decreased in the acidotic fetuses when compared with the controls. Low-to-high frequency ratio was greater in the acidotic group during the whole study period (P= 0.002). Cord artery pH was inversely associated with total fetal heart rate variability (P < 0.001), low-frequency fetal heart rate variability (P < 0.001) and low-to-high frequency ratio (P= 0.004). CONCLUSIONS: Marked fetal acidosis was associated with frequency-specific changes in fetal heart rate variability as reflecting the compensation ability of autonomic nervous activation during the last hour of labour.

Asphyxia aggravates systemic hypotension but not pulmonary hypertension in piglets with meconium aspiration.

Meconium aspiration and birth asphyxia are both separately connected to significant pulmonary and systemic hemodynamic changes in newborns, but, although these insults frequently coexist, their combined effects on the neonatal circulation are still controversial. To determine the pulmonary and systemic circulatory changes induced by pulmonary meconium contamination with concurrent asphyxia, 41 anesthetized and ventilated newborn piglets (10-12 d) were studied for 6 h. Eleven piglets were instilled with a bolus of human meconium intratracheally, and 10 piglets had meconium instillation with immediate induction of an asphyxic insult. Eight piglets had only asphyxia and 12 ventilated piglets served as controls. Meconium instillation (with and without asphyxia) resulted in a sustained decrease in the oxygenation, which remained, however, on the control level in the asphyxic group. Although meconium insufflation (with and without asphyxia) increased pulmonary artery pressure and vascular resistance progressively during the study period, the meconium-induced hypertensive effect was actually diminished by additional asphyxia. Asphyxia alone did not have any effect on these pulmonary hemodynamic parameters. On the other hand, whereas systemic arterial pressure and vascular resistance remained on the control level after meconium instillation alone, asphyxia (with and without pulmonary meconium insult) resulted in a sustained fall in systemic pressure already by 4 h. Our data thus indicate that although the coexisting asphyxia seems to moderate the meconium aspiration-induced pulmonary hypertensive response, this additional asphyxic insult does not affect the associated hypoxemia, but rather significantly exacerbates systemic hypotension.

Docetaxel does not impair cardiac autonomic function in breast cancer patients previously treated with anthracyclines.

The effects of docetaxel treatment on autonomic cardiac function was studied with 24-h ECG recordings in breast cancer patients pretreated with anthracyclines. Twenty-four women were evaluated before docetaxel treatment and after 3-4 courses of docetaxel 100 mg/m(2). The heart rate, cardiac extrasystoles and heart rate variability (HRV) in both the time and frequency domain were assessed from 24-h ECG recordings. The acute effects of docetaxel were calculated from 1-h recordings immediately prior to, during and after infusion. Long-term effects were evaluated from 24-h recordings performed before treatment and after 3-4 courses of docetaxel. There was no increase in the number of cardiac extrasystoles during docetaxel infusion. The number of ventricular extrasystoles decreased from 14 (23) to 7 (14) during and 5 (10) after the first infusion (p=0.02). The heart rate, HRV and extrasystoles were similar before and after 3-4 courses of docetaxel. The treatment did not abolish circadian variability of the heart rate. Docetaxel did not deteriorate autonomic cardiac function. In conclusion, our findings suggest that docetaxel does not have harmful cumulative effects on autonomic control of the heart and is therefore unlikely to be cardiotoxic.

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.