Recovery of the hypothalamic-pituitary-adrenal response to stress. Effect of stress intensity, stress duration and previous stress exposure

Pathological consequences of stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis may be related to the duration rather than to the intensity of HPA axis activation after exposure to the stressor. Consequently a fine analysis of post-stress events is of importance. The present experiments were designed to study the importance of three key factors in HPA recovery: intensity of the stressor (experiment 1), duration of exposure to the stressor (experiment 2) and previous experience of the animals with the situation (experiments 3 and 4). In experiment 1, analysis of both the response to the stressor and the poststress period showed that the stronger the stressor, the greater the area under the curve of HPA activation. In experiment 2, different groups of rats were exposed to different periods of immobilization (IMO) (20 min, 1 h and 2 h) and sampled before, during and after exposure to IMO. The speed of recovery of plasma corticotropin (ACTH) levels was not related to the duration of exposure to the stressor. In experiments 3 and 4, the influence of previous experience with the stressor was studied in rats daily exposed to 20 min IMO or daily injected with hypertonic saline (HS) for 8 days and sampled on days 1, 2, 5 and 8. Whereas a significant decline in plasma ACTH levels was not observed immediately after IMO until day 8, a single previous exposure to IMO was enough to enhance recovery 90 min after the end of exposure to IMO. Corticosterone levels were related to the number of previous experiences with the stressor only in the post-IMO period. In response to a novel stressor (forced swimming), chronic IMO rats showed a slightly impaired recovery as compared to stress-naive rats, suggesting that enhanced recovery of the HPA axis was specific for the homotypic stressor. After daily HS injections, a pattern similar to that after IMO was observed, the delayed, but not the early response of the HPA axis being reduced as a function of the number of previous experiences with the situation. Taken together, the present results suggest that the speed of recovery of the HPA axis after its activation by stressors is sensitive to the intensity of the stressors but not to their duration, and that adaptation to a repeated stressor is more apparent during the delayed HPA response.     

Long-duration stress

No extensive information exists in literature concerning the late or residual effects of stress on motility of small bowel and colon. Moreover, the duration and magnitude of the intestinal motor response to stress are still ignored. Therefore, the aim of our work was to determine, in rat, the effect of long-duration stress induced by restraint on the motility of small bowel and colon. Observations were made during physical restraint and 60 h later. Bipolar electrodes were implanted on the gastrointestinal serosa from the pylorus to the sigmoid colon in male Wistar rats. Electromyographic (EMG) recordings were made during fasting state, and a control EMG recording session was performed during 12 hr, followed by a 12-hr recording during restraint stress. After a 60-hr resting period, another EMG recording session was performed during 3 hr. During stress in the pylorus and small bowel, the recurrence of migrating myoelectrical complexes (MMCs) was immediately interrupted and replaced by a continuous and irregular activity. The motility index (number of spike bursts/10 min) was augmented rapidly on the jejunum and ileum, but it increased only gradually on the pylorus. Only on the transverse colon were the number of spike bursts/hour and their relative duration increased after 7 hr of physical restraint. In contrast, the sigmoid colon displayed a gradual decrease in the relative duration of contractile activity during the first 6–7 hr of stress. At 60 hr after stress in the pylorus and small bowel, a normal control motor activity was restored (MMC, motility index) on the jejunum and on the ileum, but the motility index on the pylorus was decreased. Throughout the colon, a faster motor activity as well as an increase in the number of spike bursts/hour was observed. In conclusion, a 12hr physical restraint stress induced instant drastic changes in small bowel motility, but a normal motility pattern was rapidly restored after the end of the stress period. However, on the colon, the motor changes are moderate at the beginning of the restraint period, then gradually increased with time, and were still largely persistent three days after the cessation of physical restraint.     

Pacing stress echocardiography: an alternative to pharmacologic stress testing

OBJECTIVES: We sought to evaluate the diagnostic accuracy and feasibility of bedside pacing stress echocardiography (PASE) as a potential substitute for pharmacologic stress echocardiography in patients admitted to the hospital with new-onset chest pain or worsening angina pectoris. BACKGROUND: Accurate and rapid noninvasive identification and evaluation of the extent of coronary artery disease (CAD) is essential for optimal management of these patients. METHODS: Bedside transthoracic stress echocardiography was performed in 54 consecutive patients admitted to a community hospital with new-onset chest pain, after acute myocardial infarction had been excluded. We used 10F transesophageal pacing catheters and a rapid and modified pacing protocol. The PASE results were validated in all patients by coronary angiography performed within 24 h of the test. Significant CAD was defined as > or =75% stenosis in at least one major epicardial coronary artery. RESULTS: The sensitivity of PASE for identifying patients with significant CAD was 95%, specificity was 87% and accuracy was 92%. The extent of significant CAD (single- or multivessel disease) was highly concordant with coronary angiography (kappa = 0.73, p<0.001). Pacing stress echocardiography was well tolerated, and only 4% of the patients had minor adverse events. The mean rate-pressure product at peak pacing was 22,313+/-5,357 beats/min per mm Hg, and heart rate >85% of the age-predicted target was achieved in 94% of patients. The average duration of the bedside PASE test, including image interpretation, was 38+/-6 min. CONCLUSIONS: Bedside PASE is rapid, tolerable and accurate for identification of significant CAD in patients admitted to the hospital with new-onset chest pain or worsening angina pectoris.     

Hypertension and stress

This study explores the relationship of chronic stress to hypertension. The study included 127 hospitalized and 134 outpatients of a stress treatment program and 129 "normal" persons in the general population. All subjects were matched for age, sex, and race. After three days of hospitalization, there was a 17.3% incidence of hypertension in the hospitalized patients when hypertension was defined as blood pressure levels greater than 140/90 mmHg. These data compare with a 5% and 13% incidence of hypertension in the outpatient stress and "normal" groups, respectively. The National Health Survey of 1962 indicated that 18% of the population were hypertensive. Our data indicate that the incidence of hypertension was no greater in a diagnostically established group of hospitalized stress patients than in the less stressed outpatient or an otherwise "normal" group. The frequently expressed notion that tension and chronic stress predispose a population to essential hypertension is not confirmed by this analysis.     

Bicycle stress echocardiography

Bicycle stress echocardiography involves the recording and interpretation of two-dimensional echocardiographic information before, during, and after bicycle exercise. The exercise test can be performed in the supine or upright posture. While there are important physiological differences between these two positions, they appear to provide similar diagnostic information on the presence or absence of coronary artery disease. A major advantage of bicycle stress echocardiography compared to treadmill exercise is the ability to image at peak exercise, rather than relying solely on pre- and postexercise imaging. This contributes to the greater sensitivity of the test for the detection of ischemia. The recent application of digital processing techniques may also improve sensitivity by permitting side-by-side comparison of rest and stress images. In summary, bicycle stress echocardiography is a useful tool in the management of patients with known or suspected coronary artery disease. It is a versatile and accurate technique, which competes favorably with other imaging modalities and provides information on regional and global left ventricular function.     

Dobutamine stress echocardiography

Two-dimensional echocardiography is a versatile, accurate, and readily available method for the assessment of cardiac anatomy and function, and extensive experience has been gained in the analysis of left ventricular wall motion. Using modern imaging techniques, regional as well as global wall motion analysis can be performed. Echocardiography can be used in conjunction with a protocol for either exercise or pharmacologic cardiovascular stress in order to identify the distribution and severity of coronary artery disease, with the induction of a regional wall motion abnormality being a sign of myocardial ischemia. The use of dobutamine infusion to accomplish stress echocardiography is a safe, accurate, and practical method for the diagnosis of coronary artery disease in patients unable to exercise. In addition to the evaluation of inducible ischemia, preliminary work is being performed with dobutamine stress echocardiography for the assessment of risk and patient prognosis following acute myocardial infarction and as an indication of tissue viability for myocardium that remains dysfunctional at rest following thrombolytic therapy.     

Nutrition and stress

Acute illness induces major physiological responses, which favor the adaptation of the organism to stress and injury. The metabolic response plays key roles in maintenance of vital functions and promotion of the healing mechanisms. All the components of energy expenditure are modified, particularly the resting metabolism. The regulation of carbohydrate metabolism is also markedly altered. Such patients are characterized by fasting and postprandial hyperglycemia, insulin resistance, and by a stimulation of the hepatic glucose production in fasted and fed states. Lipolysis and increased fat oxidation are typically observed. Ketogenesis processes are inhibited, concurring to alter the adaptation to starvation. Protein turnover is stimulated with a preponderance of the catabolic processes, even during full nutritional support. This induces a state of resistance to feeding, leading to a progressive depletion of the fat free mass. Such progressive tissue catabolism cannot be reversed by hypercaloric nutrition or growth factors. Specific nutrients (aminoacids, micronutrients, PUFA) may offer interesting perspectives in stimulating immunity, improving the antioxidant balance or modulating the inflammatory response.     

Chronic inflammatory stress

A major mechanism involved in maintaining homeostasis in response to chronic inflammation is the hypothalamo-pituitary-adrenal (HPA) axis, resulting in the release of anti-inflammatory glucocorticoids from the adrenal cortex. An inadequate HPA axis response may result in the development of a pathology or an increase in susceptibility and/or severity of disease. Other neuroendocrine systems are also implicated. Increasingly considered important are circadian rhythms, not only of hormones, but also of components of the immune system. Recent evidence concerning changes in hypothalamic control of the HPA axis following development of disease, the implication of these for the response to stress and the use of the HPA axis as a predictor of susceptibility to disease will also be considered. Finally, the influence of stress on autoimmune disease will be discussed. This chapter will concentrate principally on rheumatoid arthritis, although other autoimmune diseases and animal models will be discussed.     

Catecholamine stress echocardiography

Two-dimensional echocardiographic monitoring during catecholamine infusion has shown promise as a safe and accurate method for detection of coronary artery disease. The clinical application of catecholamine stress echocardiography has been facilitated by the development of digital image processing techniques. The sensitivity of this method of stress testing has been improved by drug infusion protocols that are designed to maximize myocardial stress. Recent investigations have demonstrated the value of dobutamine stress echocardiography for detection of multivessel disease following myocardial infarction and for assessment of cardiac risk before noncardiac surgery. Evaluation of changes in wall motion and thickening that occur during low dose dobutamine infusion may enable detection of viable myocardium after thrombolytic treatment of acute myocardial infarction. Compared to alternative noninvasive diagnostic methods, catecholamine stress echocardiography permits continuous acquisition of high-quality information on regional and global systolic function. This and other advantages have prompted the search for broader applications of this technique.     

Osteoporosis and stress

There may be three ways of relationship between stress and osteoporosis. The first is that stress induces some physiological changes leading to osteoporosis. The second is that stress induces behavioral distortion of eating, drinking, exercise, and sleep habits, which leads to osteoporosis. The third is that osteoporosis, on the other hand, brings about anxiety, depression, loss of social roles, and social isolation, which leads to stress. The susceptible sex and age groups are postmenopausal women and young women. The abrupt decrease of estrogen in postmenopausal women promotes reabsorption of bone, and it was also reported that the increase of interleukin-6 (IL-6) that is downstream of estrogen was related to the production of osteoclast and to the development of disability of the aged. Regarding the association with stress, while it was reported that depression or depressive states directly increased inflammation-induced cytokines including IL-6, it was also pointed out that stress-induced easy infectious may produce chronic infection, which indirectly increases inflammation-induced cytokines. Anorexia Nervosa that is assumed to be associated with adolescent developmental stress is noteworthy in young women. Amenorrhea is always present in this disease, and in addition to bone reabsorption associated with estrogen deficiency, the decrease of bone formation associated with malnutrition may be related to the development of osteoporosis.     

Acute stress cardiomyopathy

A unique syndrome of heart failure and transient left ventricular systolic dysfunction precipitated by acute emotional or physical stress has recently emerged in the medical literature. The syndrome is referred to by several names, including stress cardiomyopathy, takotsubo cardiomyopathy, left ventricular apical ballooning syndrome, and broken heart syndrome. Because most patients with stress cardiomyopathy present with chest pain, electrocardiographic abnormalities, elevated cardiac enzymes, and focal left ventricular wall motion abnormalities, it is not surprising that for years this syndrome went relatively unrecognized because physicians mistook it for acute myocardial infarction. As reports of this condition have increased worldwide during the past 5 years, it has become clear that stress cardiomyopathy has unique clinical features that can be readily distinguished from those of an acute myocardial infarction. This article reviews the clinical features of stress cardiomyopathy and discusses potential pathophysiologic mechanisms of this disorder.     

Hypertension and stress

Stress and adjustment to stress involve pathophysiological processes operating in the cardiovascular system, particularly concerning high blood pressure. Stress and high blood pressure are closely linked. Stress induces transient psychosomatic-related increases in blood pressure, but can also induce more permanent rise in blood pressure when associated with other environmental, psychological, or genetic risk factors. Symptomatic treatment of high blood pressure requires medicinal antihypertensive therapy; anti-stress therapy is an effective but not sufficient complement.