Cardiovascular System's States under Stress: Reviews of Methods.

A comparative analysis is made of various methods for processing electrocardiograms and RR-interval sequences. This analysis was carried out by using standard nonlinear-dynamics algorithms and methods. Apart from that, we assessed the expediency of using a number of characteristics to classify the cardiovascular system's state under stress.

Isatin, an endogenous monoamine oxidase inhibitor, triggers a dose- and time-dependent switch from apoptosis to necrosis in human neuroblastoma cells.

Isatin is an endogenous indole that is increased in stress, inhibits monoamine oxidase (MAO) B and improves bradykinesia and striatal dopamine levels in rat models of Parkinson's disease. Consequently, it has been suggested that isatin might be a possible treatment for Parkinson's disease although little is known about its effects on neural cell growth and survival. The aim of this study was to investigate the survival of dopaminergic human neuroblastoma (SH-SY5Y) cells following treatment with increasing concentrations of isatin. SH-SY5Y cells were exposed to isatin for defined time points, after which cell survival was determined by MTT assay. A combination of Annexin V binding and propidium iodide (PI) exclusion was used to distinguish apoptosis from necrosis in flow cytometry experiments and FACS profiles of permeabilised PI-labelled cells were employed for the assessment of cell cycle distribution. Isatin treatment (1-400 microM) for 24h induced a significant dose-dependent increase in MTT metabolism by SH-SY5Y cells in culture, but this was not due to an increase in cell division. At the higher concentrations (200-400 microm) isatin triggered cell death, although MTT metabolism was still increased in the culture, suggesting that surviving cells were hypermetabolic. Following a longer (48 h) exposure, isatin was found to cause cell death in a dose-dependent manner; at lower concentrations (50 microM), the predominant mode of cell death was apoptosis while at the highest concentration (400 microm) increasing numbers of necrotic cells were also evident. Thus, in dopaminergic SH-SY5Y cells isatin induces cell death in dose- and time-dependent manner. This death occurred as a continuum of survival, apoptosis and necrosis. Our results re-emphasise that caution should be exercised when considering high doses of isatin as a putative anti-Parkinson's disease therapeutic.

Prenatal stress alters cardiovascular responses in adult rats.

Environmental factors in early life are clearly established risk factors for cardiovascular disease in later life. Most studies have focused on nutritional programming and analysed basal cardiovascular parameters rather than responses. In the present study we have investigated whether prenatal stress has long-term effects on cardiovascular responses in adult offspring. Female pregnant Sprague-Dawley rats were subjected to stress three times daily from day 15 to day 21 of gestation. Litters from stressed and control females were cross-fostered at birth to control for mothering effects. When the offspring were 6 months old, blood pressure was measured in the conscious rats through implanted catheters at rest, during restraint stress and during recovery. Basal haemodynamic parameters were similar in the different groups but the pattern of cardiovascular responses during stress and recovery differed markedly between prenatally stressed (PS) and control animals. PS rats had higher and longer-lasting systolic arterial pressure elevations to restraint stress than control animals. They also showed elevated systolic and diastolic blood pressure values during the recovery phase. PS rats demonstrated a greater increase in blood pressure variability compared with control animals during exposure to restraint stress, and showed more prolonged heart rate responses to acute stress and delayed recovery than controls. There was no effect of prenatal stress on baroreflex regulation of heart rate. PS females showed a greater increase in systolic arterial pressure and blood pressure variability and delayed heart rate recovery following return to the home cage then did PS males. These findings demonstrate for the first time that prenatal stress can induce long-term, sex-related changes in the sensitivity of the cardiovascular system to subsequent stress.

Effects of external periodic perturbations on short-term heart rate variability in healthy subjects and ischemic heart disease patients.

AIMS: To characterise the frequency response of short-term heart rate variability to external periodic perturbations in healthy and ischemic heart disease subjects. METHODS: Eleven healthy men and 11 ischemic heart disease patients were enrolled in this study. The frequency response of heart rate variability was assessed during periodic eyes opening test and controlled breathing at frequencies ranging from 0.08 to 0.25 Hz using autoregressive spectral analysis. RESULTS: In subjects of both groups the mean heart rate and blood pressure were unchanged across experimental sessions. In healthy subjects eyes opening at rate of 8 and 6 times/min (0.12 and 0.10 Hz) evoked high-power peaks (P<0.05) at the same frequencies in the R-R power spectrum. The largest frequency response of heart rate variability was seen during eyes opening at 0.1 Hz (P<0.05). Ischemic heart disease patients failed to respond to periodic eyes opening with any changes in heart rate variability. During controlled breathing healthy subjects showed the highest heart rate variability frequency responses when breath frequency was 0.1 Hz (P<0.05). Comparatively, patients with ischemic heart disease had reduced frequency responses of heart rate variability at all breath rates and its magnitude did not depend on the perturbation frequency. CONCLUSIONS: Our results demonstrate that the frequency response of short-term heart rate variability to external periodic perturbations is dependent on the perturbation frequency and the presence disease processes in the cardiovascular system.

Comparative analysis of methods for classifying the cardiovascular system's states under stress.

A comparative analysis is made of various methods for processing electrocardiograms and RR-interval sequences. This analysis was carried out by using standard nonlinear-dynamics algorithms and methods. Apart from that, we assessed the expediency of using a number of characteristics to classify the cardiovascular system's state under stress.

Normalized entropy applied to the analysis of interindividual and gender-related differences in the cardiovascular effects of stress.

Nonlinear dynamic methods are considered to be a potential tool for studying the complex behavior of the cardiovascular system. In the present study, interindividual and gender-related differences in cardiovascular (CV) responses to various stress stimuli were studied using conventional CV variables such as heart rate (HR) and blood pressure (BP), as well as a recently introduced criterion of system complexity, normalized entropy (E/H, where E is entropy and H is system energy). A group of healthy students (n = 270) of both genders (17-20 years of age) were subjected to noise exposure, mental arithmetic, arithmetic against noise and examination stress. Results showed that CV reactivity depended upon the kind of stress imposed and the gender of the subject. HR and BP stress-induced responses did not differ between men and women. However, men had higher absolute BP levels at baseline and during exposure to stressors. Stress-induced pressor responses lasted longer in men than in women. Changes in the complexity degree of CV signals, as assessed by E/H, were more pronounced and prolonged than those of HR and BP. Unlike the latter, E/H changed significantly in all stress situations for each subject tested and could be divided into two types of stress-induced response. These results allow one to conclude that E/H can better quantitate individual differences in CV stress reactivity in comparison with HR and BP. These findings suggest that stress-induced changes in CV functioning are more varied than can be revealed by applying conventional CV measures.

[Sex differences in adrenocortical sensitivity and resistance to cerebrovascular damage in rats under strong stress]. / Polovye razlichiia adrenokortikal'noi chuvstvitel'nosti i ustoichivosti k tserebrovaskuliarnym povrezhdeniiam u krys pri sil'nom stresse.

Dynamics of changes in adrenal and plasma corticosterone and the development of cerebrovascular lesions were studied in both male and female rats, exposed to strong stress (combined immobilization and intermittent found sound for 2 hours). Plasma corticosterone levels in stressed females were 460% and 660% of the control values when measured on stress minute 10 and 120. The corresponding values in male rats were 220% and 360%. The stress-induced dilatation of brain vessels and the increases in vascular permeability were less pronounced in females than in males, when studied 0.1 and 24 hours after termination of stress. The number of brain perivascular haemorrhages was markedly reduced in females compared with males. It is supposed that higher resistance to stress-induced cerebrovascular lesions in females may be attributed to higher functional reserves of steroidogenesis.

[Sex differences in response to stress in conscious and anesthesized rats during surgical stress]. / Polovye razlichiia v stress-reaktivnosti u bodrstvuiushchikh i anestezirovannykh krys pri khirurgicheskom stresse.

Adrenal and plasma corticosterone levels under conditions of preoperative stress (removal from animal to experimental rooms, removal from a home cage, handling, weighing and injecting with saline) were more than 2-fold higher in female rats than in male ones. Females, compared with males, showed more pronounced decrease in corticosterone responses to preoperative stress and laparotomy under nembutal anesthesia, which blocked stress-induced emotional activation. One hour after recovery from anesthesia laparotomized females but not males, demonstrated a significant (5-fold) increase in plasma corticosterone level. The absolute values of plasma corticosterone in laparotomized females, compared with males, were 2-fold lower under anesthesia but 2-fold higher after recovery from anesthesia. It is supposed that in females, compared with males, stress-induced emotional tension plays more considerable role in endocrine stress responses. This provides higher adrenocortical sensitivity to stress in conscious female rats than in male animals.