Prevention of stress-related disorders in the contractile function of non-ischemic areas of the heart during myocardial infarction using gamma-hydroxybutyric acid

Contractile function of an isolated right auricle of the rat was studied one day after producing an experimental infarction of the left ventricle. It was disclosed that in this non-ischemized heart area there developed marked decrease in myocardial extensibility and depression of contractile function manifesting in an approximately two-fold lowering of the developing tension. These stress-induced disturbances prevented by administering GABA prior to myocardial infarction production. It is assumed that the action of GABA is accounted for by its capability to protect non-ischemized areas of the myocardium against harmful stress action.     

Comparative evaluation of the protective effect of adaptation to short-term stress exposures in damage to the heart and portal vein from long-term stress

The effect of the preliminary adaptation to short-term stress actions carried out under different conditions was studied in the myocardium and vascular smooth muscle damaged by long-term immobilization stress. The preliminary adaptation performed under "sparing" conditions was shown to protect more effectively the right atrial myocardium and portal vein against damages induced by long-term immobilization than that carried out under stringent conditions. The sparing adaptation allowed avoiding the appearance of the structural "price" of the adaptation, i.e. the depression of myocardial contractile function induced by adaptation itself.     

Effects of adaptation to exposure to short-term stress on indices of resistance of energy metabolism and contractile function of the myocardium to acute hypoxic hypoxia and reoxygenation

Effect of preliminary adaptation to immobilization stress with progressive duration from 15 min. to 1 h (every second day, 8 sessions) on the resistance of indices of myocardial energy metabolism and contractile function to acute hypoxic hypoxia and subsequent reoxygenation was studied. It was shown, that adaptation to short-term stress exposure by some way provided the retention of activities of important enzymes like creatine-phosphokinase and phosphorylase under the harmful action of acute hypoxia and subsequent reoxygenation. At the same time, the ATP restoration and the CP super-restoration were observed during reoxygenation. This effect, in its turn, was accompanied by a more pronounced super-restoration of the heart contractile function than in control.     

Anti-stress effect of dalargin in immobilization stress in rats

The function of the isolated perfused rat hearts was studied in four groups of experiments. Group 1--included the hearts of intact animals ("absolute control"), group 2--the hearts of rats subjected to 24 hour immobilization in supine position against the background of triple intramuscular injections of placebo (control), group 3 included the hearts of rats, which during 24 hour immobilization stress were thrice injected a synthetic analogue of endogenous opioids Dalargin in a dose of 3 g/kg, and group 4 included the hearts of animals, which during immobilization were administered Dalargin in a dose of 10 g/kg of body mass. Ulcer index as indicator of stress injury of gastric mucosa was also determined. In the control group of experiments (group 2) 24 hour immobilization stress resulted in complete depression of cardiac performance as compared with group 1, and ulcer index approximated 1. In group 3 the indices of cardiac performance even exceeded those in group 1 (intact animals). As compared with group 2, ulcer index in group 3 decreased by 9 times. In application of Dalargin in a dose of 10 g/kg complete preservation of heart function indices and complete prevention of stress injury of gastric mucosa were also observed. Thus, Dalargin possesses cardioprotective and anti-ulcerogenic effect in immobilization stress in rats. Most probably, this phenomenon can be attributed to its ability to inhibit the activity of sympathoadrenal system, which gets enhanced during stress.     

Prevention of stress-induced disorders of myocardial contractile function by using sparing adaptation to short-term stress effects

Adaptation to repeated short-term stress is known to prevent to a considerable extent the depression of the myocardial contractile function which usually develops under long-term stress. But the adaptation itself has a "cost", i. e. it results in limited but significant disturbances of myocardial contractile function. The present review documents the method of adaptation involving few actions with prolonged intervals between them. It has been established that such an adaptation per se does not induce any disturbances of contractile function. At the same time it prevents completely the depression of contractile function caused by stress.     

Effects of two types of restraint stress on spontaneous behavior of Sprague-Dawley and Lewis rats.

The purpose of this study was to evaluate the action of two types of stressors in Sprague-Dawley (S-D) and Lewis (LEW) rats differing in their hypothalamic-pituitary-adrenal axis activity on locomotion and rearing in an open space. Exposure to restraint immobilization alone (IMO) or this immobilization combined with cold water (22 degrees C) immersion (IMO+C) lasted for 1 h and started 2 or 5 h before the test. To evaluate the acute and persisting effects of both stressors, four trials were performed in one-week intervals; rats were exposed to the stressors in trial 1 and 3. While in LEW rats both acute stressors produced reduction of locomotion and rearing in all stressed groups, S-D rats responded with a decrease of both parameters only after IMO+C presented 2 h before testing. Neither strain displayed a changed performance one week after the first stress exposure. One week after the second stress exposure rats of both strains exhibited a tendency to an increase of both parameters reaching the significance in several experimental groups. The findings indicate: a) the IMO+C produced stronger behavioral alteration than IMO alone; b) the behavioral responses to stressors were more pronounced in LEW compared to S-D strain; c) change from the reduction of activity to its increase may be interpreted as bi-directional manifestation of long-term effects of immobilization stress.     

The mechanism of the duodenal motility strengthening under psychogenic stress in rabbits

In experiments on unanaesthetized rabbits, myoelectric activity (contractile activity index) of two sites of duodenum and of antral and pyloric parts of the stomach was studied under stress induced by fastening a rabbit to a table in supine position. In both sites of duodenum, the stress impact induced a short-time inhibition of contractile activity which was followed by its strengthening that exceeded the initial level. Meanwhile in antrum and pylorus, the whole period of stress impact was characterized by suppression of contractile activity, the latter being more pronounced in the antrum. The strengthening of the duodenal contractile activity was preserved after muscarinic ornicotinic cholinoceptor blockade. It was concluded that the contractile response of duodenum seemed to be of humoral origin.     

The electron microscopic characteristics of stress lung

The influence of long-term (6 hours) immobilization stress on morphofunctional state of lung air-blood barrier was studied in experiments of the rats. It was shown that stress provoked the marked ultrastructural changes in the lungs, which were as follows: lung tissue oedema, pronounced thickening of lung air-blood barrier and its separate layers, edema-hemorrhagic syndrome, alveolar epithelial injury, disturbance of lung surfactant systems. Such a pathological complex may be designated as a "stress lung".     

Prevention of disorders in the contractile function of the nonischemic portion of the heart during infarction by preliminary adaptation to brief stress exposures

Preliminary adaptation to short-term exposures to immobilization stress prevents to a large extent the depression of contractile function and the lowering of the right atrium myocardium resistance to hypoxia and excess Ca2+ in experimental infarction of the left ventricle. This fact agrees with the concept that disturbance occurring in the nonischemic heart during infarction is caused by stress-induced damage.     

Altered muscle force and stiffness of skeletal muscles in alpha-sarcoglycan-deficient mice

Alpha-sarcoglycan (ASG) is a transmembrane protein of the dystrophin-associated complex, and absence of ASG causes limb-girdle muscular dystrophy. We hypothesize that disruption of the sarcoglycan complex may alter muscle extensibility and disrupt the coupling between passive transverse and axial contractile elements in the diaphragm. We determined the length-tension relationships of the diaphragm of young ASG-deficient mice and their controls during uniaxial and biaxial loading. We also determined the isometric contractile properties of the diaphragm muscles from mutant and normal mice in the absence and presence of passive transverse stress. We found that the diaphragm muscles of the null mutants for the protein ASG show 1) significant decrease in muscle extensibility in the directions of the muscle fibers and transverse to fibers, 2) significant reductions in force-generating capacity, and 3) significant reductions in coupling between longitudinal and transverse properties. Thus these findings suggest that the sarcoglycan complex serves a mechanical function in the diaphragm by contributing to muscle passive stiffness and to the modulation of the contractile properties of the muscle.     

The new clinical standard of integrated quadruple stress echocardiography with ABCD protocol

Background

The detection of regional wall motion abnormalities is the cornerstone of stress echocardiography. Today, stress echo shows increasing trends of utilization due to growing concerns for radiation risk, higher cost and stronger environmental impact of competing techniques. However, it has also limitations: underused ability to identify factors of clinical vulnerability outside coronary artery stenosis; operator-dependence; low positivity rate in contemporary populations; intermediate risk associated with a negative test; limited value of wall motion beyond coronary artery disease. Nevertheless, stress echo has potential to adapt to a changing environment and overcome its current limitations.

Integrated-quadruple stress-echo

Four parameters now converge conceptually, logistically, and methodologically in the Integrated Quadruple (IQ)-stress echo. They are: 1- regional wall motion abnormalities; 2-B-lines measured by lung ultrasound; 3-left ventricular contractile reserve assessed as the stress/rest ratio of force (systolic arterial pressure by cuff sphygmomanometer/end-systolic volume from 2D); 4- coronary flow velocity reserve on left anterior descending coronary artery (with color-Doppler guided pulsed wave Doppler). IQ-Stress echo allows a synoptic functional assessment of epicardial coronary artery stenosis (wall motion), lung water (B-lines), myocardial function (left ventricular contractile reserve) and coronary small vessels (coronary flow velocity reserve in mid or distal left anterior descending artery). In “ABCD” protocol, A stands for Asynergy (ischemic vs non-ischemic heart); B for B-lines (wet vs dry lung); C for Contractile reserve (weak vs strong heart); D for Doppler flowmetry (warm vs cold heart, since the hyperemic blood flow increases the local temperature of the myocardium). From the technical (acquisition/analysis) viewpoint and required training, B-lines are the kindergarten, left ventricular contractile reserve the primary (for acquisition) and secondary (for analysis) school, wall motion the university, and coronary flow velocity reserve the PhD program of stress echo.

Conclusion

Stress echo is changing. As an old landline telephone with only one function, yesterday stress echo used one sign (regional wall motion abnormalities) for one patient with coronary artery disease. As a versatile smart-phone with multiple applications, stress echo today uses many signs for different pathophysiological and clinical targets. Large scale effectiveness studies are now in progress in the Stress Echo2020 project with the omnivorous “ABCD” protocol.

     

Immobilization stress reduces oxygen consumption of the isolated interstitial rats' testes cells

The aim of this study was to investigate the effects of acute and repeated immobilization stress on oxygen consumption (QO2) of the isolated interstitial rats' testes cells (ISC). The oxygen consumption by ISC testes was measured in vitro with a Clark-type oxygen electrode. Acute immobilization stress (2 h) induced decrease in QO2 (-49% V4, -31% V3) which was statistically significant (p<0.01). Repeated immobilization stress (2 hours daily for 10 consecutive days) induced a fall in QO2 (-10% V4, -4% V3) but this inhibition of respiration was not statistically significant (p>0.05). The mechanisms by which immobilization stress induces mitochondrial dysfunction as well as mechanisms which develop an adaptive response to repeated immobilization remain unclear, so that further investigations of this mechanisms are required.     

Inhibition of the rat adrenal ornithine decarboxylase activity by immobilization stress and/or dexamethasone

The effects of immobilization stress and/or dexamethasone (DEX) on the adrenal ornithine decarboxylase (ODC) activities of sham-operated and adrenal-medulloectomized (enucleated) male Sprague-Dawley rats were investigated. On day 11 after surgery, rats were injected with saline or DEX (1 mg/kg), 3 h before the time of sacrifice (0600 h or 1800 h). Four groups, from sham-operated and enucleated rats (ENU) treated with saline or DEX were subjected to immobilization stress for 1 h prior to sacrifice. Groups of rats from stress-sham-DEX, non stress-sham-DEX, stress-sham, non stress-sham, stress-ENU-DEX, non stress-ENU-DEX, stress-ENU, and non stress-ENU were sacrificed at 0600 h or 1800 h on day 11 after surgery. Adrenal glands were excised and later analyzed for ODC activities. Results indicated that DEX and/or immobilization stress inhibited ODC activities (p < 0.05) in normal and regenerating adrenal glands at 1800 h and ODC activity varies diurnally, the activity being greater at 1800 h than at 0600 hours (p < 0.001).     

Participation of ATP-sensitive potassium channel in autoregulation of coronary blood flow under the condition of limited motor activity

The aim of study involved detection of the effect of the K(ATP)-channel blocker glibenclamide on autoregulation of coronary flow, the expression of reactive hyperemia, the value of coronary dilatation reserve, and the myocardial contractile function in isolated rat hearts after a 6-hour immobilization stress. The experiments have been performed on 64 isolated rat hearts (female): into the cavity of left ventricle, a latex balloon connected with electromanometer has been introduced. Every experiment consisted of 2 stages. The heart has been perfused by Krebs-Henseleite solution in the first stage, and in the second stage--by the same solution with glibenclamide (1 mkM) or its combination with verapamile (10(-)6 M) or saponin (44 mcg/ml of coronary flow within 2 minutes) added to it. During the experiment, the perfusion pressure has been elevated step by step from 40 to 120 mm Hg with 20 mm Hg steps (coronary autoregulation). In rats after immobilization, the glibenclamide effect on cardiac vessel tone and expression of maximal hyperemic coronary flow (in contrast to its influence on myocardial contractile function) is lower than in control and depends on endotheliocyte presence which suggests an important role of endothelium in maintaining cardiac vessel smooth cell activity of K(ATP)-channels inhibited under the stress condition. After immobilization stress, the role of endothelium in the reactive hyperemia origin was enhanced, that of the K(ATP)-channels was reduced. The general activity of both mechanisms of tone regulation of cardiac vessels remains the same as in control. This suggests that the K(ATP)-channels as nitric monoxide and eicozanoids are the local system of myogenic tone regulation of the rat cardiac vessels; that the rat immobilization inhibits the activity KATp-channel's smooth cells of coronary vessels and creates a marked dependence of their activity on endothelium presence.     

Prenatal stress and glucocorticoid effects on the developing gender-related brainProceedings of Xth International Congress on Hormonal Steroids, Quebec, Canada, 17–21 June 1998.

Hormonal and neurotransmitter environment of nondifferentiated cells in the developing brain determines many of gender-specific behavioural and neuroendocrine functions. Early postnatal and long-term effects of maternal stress or prenatal glucocorticoid on sex-related peculiarities of the brain morphology, biogenic monoamine turnover, testosterone metabolism, hypothalamic noradrenaline (NA) and adrenocortical responses to an acute stress were studied in Wistar rat offsprings. Maternal stress (1 h immobilization daily for gestational days 15–21) prevented development of sexual dimorphism in neuronal cell nuclei volumes in suprachiazmatic nucleus (SCN) in 10 day old pups. That was associated with a disappearance of male–female differences in NA and 5-hydroxytryptamine turnover in the preoptic area (POA) and dopamine (DA) turnover in the mediobasal hypothalamus (MBH) by decreasing them in male pups. Hydrocortisone acetate (5 mg daily during the last week of pregnancy) produced changes in NA turnover in the POA of males and females which were quite similar to those after maternal stress. Changes in aromatase and 5-reductase activities in the POA of male pups were quite opposite as affected by maternal stress or prenatal glucocorticoid. Sexual differences in 5-reductase activity in the MBH appeared due to its increase in prenatally stressed male pups. In contrast to adult males, in adult females maternal stress did not restrict hypothalamic NA and blood plasma corticosterone response to acute stress (1 h immobilization). Our findings on morphology and functions of gender-related developing brain areas stand in correlation with modifying effects of maternal stress and prenatal glucocorticoid on behavior and neuroendocrine regulations.     

Mechanism of strengthening of the contractile activity in the duodenum and in the jejunum in psychogenic stress in rabbits

In experiments on unanaesthetized rabbits myoelectric activity (contractile activity index) of proximal (postpyloric) and distal sites of duodenum, and proximal part of jejunum was studied under stress induced by fastening a rabbit to a table in supine position. In both sites of duodenum, the stress impact induced a short-time decrease of contractile activity which was followed by its increase that exceeded the initial level. In the proximal part ofjejunum, the increase of contractile activity took place only during the second part of stress response. The strengthening of the contractile activity of the proximal part of duodenum was preserved after muscarinic or nicotinic cholinoceptor blockage, and after beta-receptor blockage. It was concluded that the contractile response of the proximal part of duodenum did not result from the contribution of central or local neurogenic mechanism, including excitatory cholinergic one, but was humoral in origin. The strengthening of the contractile activity of the distal part of duodenum and proximal part ofjejunum was abolished by muscarinic cholinoceptor and beta-receptor blockage, and resulted from the action of circulating catecholamines on the excitatory beta-adrenoceptor, localized on the cholinergic neurones of the enteric nervous system.     

Immobilization stress induces XBP1 splicing in the mouse brain

Cells activate the unfolded protein response (UPR) to cope with endoplasmic reticulum (ER) stress. In the present study, we investigated the possible involvement of psychological stress on UPR induction in the mouse brain. When mice were exposed to immobilization stress for 8?h, XBP1 mRNA splicing was significantly induced in the hippocampus, cortex, hypothalamus, cerebellum, and brain stem. On the other hand, we did not observe any increase in XBP1 splicing in the liver, suggesting that this effect is specific to the brain. Stress-induced XBP1 splicing was attenuated 2 days after immobilization stress. We did not observe increases in any other UPR genes, such as CHOP or GRP78, in mouse brains after immobilization stress. These findings indicate an important specific role of XBP1 in response to psychological stress in the mouse brain.     

Effect of stress-inducing factors on the behavior of monkeys. I. The behavior of monkeys under acute emotional stress

The behavior of Papio hamadryas pubertal males under the immobilizational stress conditions has been studied. It has been established that this very type of stress appeared to be a powerful irritant for the individuals of this species and age leading them into the depression state. The process of normalization of behavior after the 2-hour immobilization lasted for about 72 h. The main consequences of the stress were the violation of locomotion, the reception by individuals of unnatural postures, the trembling of limbs and the violation of coordination. The reaction of stress was greatly influenced by the position of individual in the hierarchic system. The dominant (alpha) and the most subdominant (z) males bore the stress easier. The intensification of food activity was marked within the male z. In certain period after the immobilization the tendency of the growth of friendly contacts between the individuals was found. The frequency of aggressive behavior after the stress lowered. The violation of manipulation activity was also marked. These regularities are of great importance for the reconstruction of group social behavior models of protohominid's societies.     

Effects of SP1-11 and its N-terminal fragment SP1-4 on several indices of the microcirculatory system in stress]

In the experiments on rats it was shown that 5-hour immobilization induced the disturbances of terminal blood flow, degranulation of mast cells, increase of venular permeability and contractile activity of lymphaticus. I/p injection SP1-11 (125 micrograms/kg) before stress aggravated the disturbances caused by immobilization. The prophylactic i/p injection SP1-4 induced tranquilizing (100%), sedative (30%) or narcosis (20%) effect. In the rats with sedative or narcosis effects the relative normalization of components of microcirculatory system was observed.     

Time course of vasopressin and oxytocin secretion after stress in adrenalectomized rats.

To characterize the participation of vasopressin (AVP) and oxytocin (OT) in hypothalamus-pituitary-adrenal regulation after adrenalectomy (ADX), we evaluated corticosterone, ACTH, AVP and OT plasma concentrations and AVP and OT content of the paraventricular nucleus (PVN) at different periods (3 h, 1, 3, 7 and 14 days) in sham or ADX rats under basal conditions and after immobilization stress. ADX animals showed undetectable corticosterone levels, while sham animals showed a marked increase in corticosterone and ACTH 3 h after surgery, then lowering to basal control levels. ADX rats showed high basal ACTH levels with a triphasic response without changes after immobilization. After three hours, the ADX group showed higher OT levels than the sham group. OT was increased after immobilization stress in sham and ADX groups. AVP plasma levels did not change throughout the basal or stress studies in either group. There was a decrease in hypothalamic AVP content 1 and 3 days after ADX under basal and stress conditions. Plasma osmolality showed a significant decrease in the ADX group at 3, 7, and 14 days. In conclusion, there are different pituitary-adrenal axis set points after removal of the glucocorticoid negative feedback. The role of vasopressinergic and oxytocinergic neurons in the ACTH secretion after ADX or immobilization stress appears to differ. Magnocellular AVP is unlikely to contribute to ACTH secretion in response to ADX or immobilization stress. On the other hand, OT is elicited by immobilization stress and might contribute to the ACTH secretion during short-term ADX.