Assessment of autonomic cardiovascular indices in non-stationary data in rats

The analysis of heart rate in the frequency domain has become increasingly important in physiological studies, and supports the use of heart rate variability as an index of autonomic cardiovascular control. A new index, the instant centre frequency (ICF) has been proposed as a global index of the instantaneous relationship between sympathetic and vagal modulation. The aim of this study was to assess ICF, RR intervals, and heart rate variability measures as indices of sympathovagal balance during a pharmacological blockade of the autonomic nervous system in normotensive rats. RR intervals and arterial blood pressure of 10 conscious Wistar rats equipped with telemetry probes, were evaluated before, during, and after injection of: (1) saline (100 microl kg(-1) i.v.); (2) phentolamine (5 mg kg(-1) i.v.); (3) atropine methyl nitrate (0.5 mg kg(-1) i.v.); and (4) atenolol (1 mg kg(-1) i.v.). RR interval series were analysed by the smoothed pseudo-Wigner-Ville distribution. A general linearised model was used to evaluate the parameters. ICF was calculated in the same way as the peak power frequency by use of the first moment of instant spectrum. We calculated the ICF of the whole spectrum (ICF(T)), ICF in high frequency (ICF(H)) and ICF in low frequency (ICF(L)). The RR intervals and ICF indexes varied similarly and presented the lowest coefficient of variation among animals exposed to the same autonomic conditions. ICF(T)-ICF(L) and ICF(H)-ICF(T) were strongly correlated with normalised HF and normalised LF. In normotensive rats, RR intervals and ICF indices may reliably capture the effects of the sympathetic and parasympathetic nervous system on the sinus node.     

Exercise training changes autonomic cardiovascular balance in mice.

Experiments were performed to investigate the influence of exercise training on cardiovascular function in mice. Heart rate, arterial pressure, baroreflex sensitivity, and autonomic control of heart rate were measured in conscious, unrestrained male C57/6J sedentary (n = 8) and trained mice (n = 8). The exercise training protocol used a treadmill (1 h/day; 5 days/wk for 4 wk). Baroreflex sensitivity was evaluated by the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine, respectively. Autonomic control of heart rate and intrinsic heart rate were determined by use of methylatropine and propranolol. Resting bradycardia was observed in trained mice compared with sedentary animals [485 +/- 9 vs. 612 +/- 5 beats/min (bpm)], whereas mean arterial pressure was not different between the groups (106 +/- 2 vs. 108 +/- 3 mmHg). Baroreflex-mediated tachycardia was significantly enhanced in the trained group (6.97 +/- 0.97 vs. 1.6 +/- 0.21 bpm/mmHg, trained vs. sedentary), whereas baroreflex-mediated bradycardia was not altered by training. The tachycardia induced by methylatropine was significantly increased in trained animals (139 +/- 12 vs. 40 +/- 9 bpm, trained vs. sedentary), whereas the propranolol effect was significantly reduced in the trained group (49 +/- 11 vs. 97 +/- 11 bpm, trained vs. sedentary). Intrinsic heart rate was similar between groups. In conclusion, dynamic exercise training in mice induced a resting bradycardia and an improvement in baroreflex-mediated tachycardia. These changes are likely related to an increased vagal and decreased sympathetic tone, similar to the exercise response observed in humans.     

Effect of acute hyperlipidemia on autonomic and cardiovascular control in humans.

Blood lipids may detrimentally affect autonomic and circulatory control. We tested the hypotheses that acute elevations in free fatty acids and triglycerides (acute hyperlipidemia) impair baroreflex control of cardiac period [cardiovagal baroreflex sensitivity (BRS)] and muscle sympathetic nerve activity (MSNA: sympathetic BRS), increase MSNA at rest, and augment physiological responses to exercise. Eighteen young adults were examined in this randomized, double-blinded, and placebo-controlled study. BRS was determined using the modified Oxford technique before (pre) and 60 min (post) after initiating infusion of Intralipid (0.8 ml x m(-2) x min(-1)) and heparin (1,000 U/h) (experimental; n = 12) to induce acute hyperlipidemia, or saline (0.8 ml x m(-2) x min(-1)) and heparin (1,000 U/h) (control; n = 6). Responses to isometric handgrip to fatigue (IHG) were also determined. Blood pressure increased more (P < 0.05) in experimental than control subjects during the infusion. MSNA at rest (14 +/- 2 vs. 11 +/- 1 bursts/min), cardiovagal (19.8 +/- 1.8 vs. 19.1 +/- 2.4 ms/mmHg pre and post, respectively) and sympathetic BRS (-5.5 +/- 0.6 vs. -5.2 +/- 0.4 au x beat(-1) x mmHg(-1)), and the neural and cardiovascular responses to IHG were unchanged by acute hyperlipidemia (pre vs. post) in experimental subjects. Similarly, MSNA at rest (10 +/- 2 vs. 12 +/- 2 bursts/min), cardiovagal (22.1 +/- 4.0 vs. 21.0 +/- 4.6 ms/mmHg) and sympathetic BRS (-5.8 +/- 0.5 vs. -5.5 +/- 0.5 au x beat(-1) x mmHg(-1)), and the neural and cardiovascular responses to IHG were unchanged by the infusion in control subjects. These data do not provide experimental support for the concept that acute hyperlipidemia impairs reflex cardiovagal or sympathetic regulation in humans.     

Functional neuroimaging of emotional learning and autonomic reactions

This article provides a selective overview of the functional neuroimaging literature with an emphasis on emotional activation processes. Emotions are fast and flexible response systems that provide basic tendencies for adaptive action. From the range of involved component functions, we first discuss selected automatic mechanisms that control basic adaptational changes. Second, we illustrate how neuroimaging work has contributed to the mapping of the network components associated with basic emotion families (fear, anger, disgust, happiness), and secondary dimensional concepts that organise the meaning space for subjective experience and verbal labels (emotional valence, activity/intensity, approach/withdrawal, etc.). Third, results and methodological difficulties are discussed in view of own neuroimaging experiments that investigated the component functions involved in emotional learning. The amygdala, prefrontal cortex, and striatum form a network of reciprocal connections that show topographically distinct patterns of activity as a correlate of up and down regulation processes during an emotional episode. Emotional modulations of other brain systems have attracted recent research interests. Emotional neuroimaging calls for more representative designs that highlight the modulatory influences of regulation strategies and socio-cultural factors responsible for inhibitory control and extinction. We conclude by emphasising the relevance of the temporal process dynamics of emotional activations that may provide improved prediction of individual differences in emotionality.     

Nine months in space: effects on human autonomic cardiovascular regulation.

We studied three Russian cosmonauts to better understand how long-term exposure to microgravity affects autonomic cardiovascular control. We recorded the electrocardiogram, finger photoplethysmographic pressure, and respiratory flow before, during, and after two 9-mo missions to the Russian space station Mir. Measurements were made during four modes of breathing: 1) uncontrolled spontaneous breathing; 2) stepwise breathing at six different frequencies; 3) fixed-frequency breathing; and 4) random-frequency breathing. R wave-to-R wave (R-R) interval standard deviations decreased in all and respiratory frequency R-R interval spectral power decreased in two cosmonauts in space. Two weeks after the cosmonauts returned to Earth, R-R interval spectral power was decreased, and systolic pressure spectral power was increased in all. The transfer function between systolic pressures and R-R intervals was reduced in-flight, was reduced further the day after landing, and had not returned to preflight levels by 14 days after landing. Our results suggest that long-duration spaceflight reduces vagal-cardiac nerve traffic and decreases vagal baroreflex gain and that these changes may persist as long as 2 wk after return to Earth.     

Renin-angiotensin and autonomic mechanisms in cardiovascular homeostasis during haemorrhage in fetal and neonatal sheep.

The present study examined the roles of the renin-angiotensin and autonomic nervous systems in cardiovascular homeostasis during slow progressive haemorrhage (20% of measured blood volume over 1h) in fetal (128-132 and 143-148 days gestation) and neonatal (5-9 and 12-20 days post-natal) sheep. Basal plasma renin activity (PRA) was not significantly different in the 4 sheep groups and increased to a similar degree (approximately 2 to 3-fold) during haemorrhage. Mean arterial pressure (MAP) exhibited modest falls in response to haemorrhage in all sheep groups and while heart rate (HR) was well maintained in the fetal groups there was a tendency to bradycardia in neonates. None of these responses was significantly different in age-matched fetal sheep subjected to bilateral vago-sympathectomy, cervical cord transection or bilateral nephrectomy, with the exception of PRA in the latter group which was close to zero throughout. Treatment with the angiotensin II (AII) antagonist, (Sar1-Ala8) AII (Saralasin), significantly increased basal PRA in both fetal and neonatal sheep (approximately 5 to 7-fold). The PRA response to haemorrhage was absent in neonatal sheep treated with Saralasin but significantly increased in fetal sheep. Saralasin significantly reduced resting MAP in both sheep groups and increased the hypotensive and bradycardic effects of haemorrhage in neonatal (approximately 3 to 5-fold) but not fetal sheep. It is concluded that in the perinatal period studied, fetal and neonatal sheep are equally well able to maintain cardiovascular homeostasis in response to moderate haemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age dependency of cardiovascular autonomic responses to head-up tilt in healthy subjects.

In elderly subjects, heart rate responses to postural change are attenuated, whereas their vascular responses are augmented. Altered strategy in maintaining blood pressure homeostasis during upright position may result from various cardiovascular changes, including age-related cardiovascular autonomic dysfunction. This exploratory study was conducted to evaluate impact of age on cardiovascular autonomic responses to head-up tilt (HUT) in healthy subjects covering a wide age range. The study population consisted of 63 healthy, normal-weight, nonsmoking subjects aged 23-77 yr. Five-minute electrocardiogram and finger blood pressure recordings were performed in the supine position and in the upright position 5 min after 70 degrees HUT. Stroke volume was assessed from noninvasive blood pressure signals by the arterial pulse contour method. Heart rate variability (HRV) and systolic blood pressure variability (SBPV) were analyzed by using spectral analysis, and baroreflex sensitivity (BRS) was assessed by using sequence and cross-spectral methods. Cardiovascular autonomic activation during HUT consisted of decreases in HRV and BRS and an increase in SBPV. These changes became attenuated with aging. Age correlated significantly with amplitude of HUT-stimulated response of the high-frequency component (r = -0.61, P < 0.001) and the ratio of low-frequency to high-frequency power of HRV (r = -0.31, P < 0.05) and indexes of BRS (local BRS: r = -0.62, P < 0.001; cross-spectral baroreflex sensitivity in the low-frequency range: r = -0.38, P < 0.01). Blood pressure in the upright position was maintained well irrespective of age. However, the HUT-induced increase in heart rate was more pronounced in the younger subjects, whereas the increase in peripheral resistance was predominantly observed in the older subjects. Thus it is likely that whereas the dynamic capacity of cardiac autonomic regulation decreases, vascular responses related to vasoactive mechanisms and vascular sympathetic regulation become augmented with increasing age.     

Gender differences in autonomic cardiovascular regulation: spectral, hormonal, and hemodynamic indexes.

The autonomic nervous system drives variability in heart rate, vascular tone, cardiac ejection, and arterial pressure, but gender differences in autonomic regulation of the latter three parameters are not well documented. In addition to mean values, we used spectral analysis to calculate variability in arterial pressure, heart rate (R-R interval, RRI), stroke volume, and total peripheral resistance (TPR) and measured circulating levels of catecholamines and pancreatic polypeptide in two groups of 25 +/- 1.2-yr-old, healthy men and healthy follicular-phase women (40 total subjects, 10 men and 10 women per group). Group 1 subjects were studied supine, before and after beta- and muscarinic autonomic blockades, administered singly and together on separate days of study. Group 2 subjects were studied supine and drug free with the additional measurement of skin perfusion. In the unblocked state, we found that circulating levels of epinephrine and total spectral power of stroke volume, TPR, and skin perfusion ranged from two to six times greater in men than in women. The difference (men > women) in spectral power of TPR was maintained after beta- and muscarinic blockades, suggesting that the greater oscillations of vascular resistance in men may be alpha-adrenergically mediated. Men exhibited muscarinic buffering of mean TPR whereas women exhibited beta-adrenergic buffering of mean TPR as well as TPR and heart rate oscillations. Women had a greater distribution of RRI power in the breathing frequency range and a less negative slope of ln RRI power vs. ln frequency, both indicators that parasympathetic stimuli were the dominant influence on women's heart rate variability. The results of our study suggest a predominance of sympathetic vascular regulation in men compared with a dominant parasympathetic influence on heart rate regulation in women.     

Significance of the endo-vinyl group of bilirubin in photochemical reactions.

In photochemical experiments on bilirubin III alpha (no endo-vinyl group), IX alpha (one endo-vinyl group) and XIII alpha (two endo-vinyl groups) and in the photochemical, thermal and catalytical reversion of their photoproducts under anaerobic conditions, much more instability and complexity of photoproducts of bilirubin XIII alpha were observed than for those of bilirubin IX alpha or III alpha. On the basis of present and previous results of photochemical experiments in vitro and the fact that large amounts of (EZ)-cyclobilirubin IX alpha appear in the bile during phototherapy of neonatal hyperbilirubinaemia [Onishi, Kawade, Itoh, Isobe & Sugiyama (1980) Biochem. J. 190, 527-532], it is concluded that the endo-vinyl group plays a crucial role in the photochemical reaction of bilirubin IX alpha. On reversed-phase high-pressure liquid chromatography of photoisomers, it was found that the retention times of geometric isomers and E-cyclized structural isomers were shortened compared with those of Z-isomer and E-isomer, respectively, as precursor substances.     

Effects of dietary copper on human autonomic cardiovascular function

Heart rate and blood pressure responses during supine rest, orthostasis, and sustained handgrip exercise at 30% maximal voluntary contraction were determined in eight healthy women aged 18-36 years who consumed diets varying in copper and ascorbic acid content. Copper retention and plasma copper concentration were not affected by diet. Enzymatic, but not immunoreactive, ceruloplasmin was lower (p less than 0.05) after the low copper and high ascorbic acid diet periods. Diet had no effect on resting supine heart rates, orthostatic responses in heart rate and blood pressure, or standing resting blood pressure. Systolic and diastolic blood pressures were increased significantly (p less than 0.05) during the handgrip test at the end of the low copper and ascorbic acid supplementation periods. Also, the ratio of enzymatic to immunoreactive ceruloplasmin decreased significantly during these dietary treatments. The mean arterial blood pressure at the end of the handgrip test was negatively (p less than 0.0004) correlated with the ceruloplasmin ratios. These findings indicate a functional alteration in human blood pressure regulation during mild copper depletion.