**1. Introduction**

A stress response is an evolutionary heritage of ability to anticipate, identify and effectively respond to danger. After millions of years of evolution, perception of variety of stressors mobilizes neurologic, neuroendocrine, endocrine, immunologic and metabolic systems to maintain an ability to survive and propagate gens (natural selection). Additionally, in humans these mechanisms involve complex and interrelated mental, emotional, behavioral and social processes. Behavioral adaptation is aimed on modulation of neural pathways that help to cope with stressful situations. These e.g. include changes of sensory thresholds, increased alertness, memory enhancement, suppression of hunger, and stress-induced analgesia.

A stressor can be defined as a certain stimulus of the external or internal receptor. The stressors are usually divided into macroscopic threats (e.g. fight with enemy, fear, pain) and microscopic threats (targeting at epithelial or endothelial barriers e.g. infection or tissue damage). These neuroendocrine – immunologic interrelations are also vital in the clinical situations. During an acute stress response, physiological processes are aimed on redistribution of energy utilization in specific organs, inhibiting or stimulating energy mobilization. Therefore certain tissues receive sufficient supply of energy while others reduce their consumption according to priority. This is achieved mainly by: the sympathetic nervous system (SNS), release of catecholamines which inhibit insulin release and action, stimulates glucagon and ACTH production; hypothalamic – pituitary – adrenocortical (HPA) axis that in general increases gluconeogenesis and glycogenolysis, inhibits glucose uptake, and enhances proteolysis and lipolysis; hypothalamic - posterior pituitary (ADH) – kidney axis with water retention; brain – juxta-gromelular apparatus activity - (renin/ angiotensin/aldosterone - RAAS) with many effects on blood pressure, electrolytes and water balance; hypothalamic-pituitary-thyroid axis (response to cold and heat), natriuretic

© 2012 Kolcz, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 Kolcz, licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

peptides, the parasympathetic nervous system (acetylcholine release), changes in immune system (cytokines and other pro-inflammatory substances), mediators of endothelial function and mobilization of stem cells.

Neuroendocrine Regulation of Stress Response in Clinical Models 5

Increase of protein catabolism in all tissues Enhancement of protein synthesis in the

Expression of adrenergic receptors Activation of renin – angiotensin –

Decrease of circulating lymphocytes,

phagocytosis, leucocyte demargination,

monocytes and eosinophils Apoptosis induction

interleukine synthesis

aldosterone system

Action Mechanism

Growth inhibition Decrease of DNA and RNA synthesis

Substrates availability increase Glycolysis, lipolysis, protein hydrolysis

Inhibition of constitutive functions Suppression of immune response

Anti-inflammatory Decrease of capillary permeability,

Water balance Sodium and water reabsorbtion

levels of plasma norepinephrine are an independent predictor of mortality.

Sympathetic nervous system stimulation is a part of central regulatory mechanism. It exerts many effects on the cardiovascular system by norepinephrine and epinephrine. Afferent baroreceptor signaling to the brain signals low cardiac output and efferent sympathetic pathways are activated. The main results of it are vasoconstriction (increased afterload, decreased renal perfusion), increased heart rate and contractility (increased cardiac output and wall stress), activation of RAAS. These effects are aimed on restoration of cardiac output, however, at the expense of increased myocardial oxygen demand, increased intracellular calcium toxicity, and myocardial hypertrophy. Sympathetic overstimulation can cause many undesirable effects like: expression of fetal gens, apoptosis, necrosis and remodeling and high

In clinical model of univentricular circulation characterized by increased afterload and normal saturation interesting behavioral adaptation was observed. During the exercise the heart rate at anaerobic threshold was significantly slower and patients' lung tidal volume lower compared to healthy age matched volunteers. These differences disappeared at peak effort. The effect was associated with a delayed chronotropic response of the heart and a reaction which provides a longer filling time and larger preload to the single ventricle. Delayed chronotropic response, earlier achievement of anaerobic threshold and higher value of ventilator equivalent of carbon dioxide at peak exercise obviously reflect greater impairment of cardiac output in single ventricle patients compared to healthy volunteers. The limitation of the exercise capacity is

**Table 1.** Role of the cortisol in stress response initiation.

**3. Sympathetic nervous system** 

Blood pressure increase Vascular tone increase,

liver

In the clinical settings, variety of interesting models and complex relations can be investigated. In particular, pathophysiology and treatment of congenital heart defects create unique models of stress response. Hypoxia, circulatory insufficiency, volume or pressure overload, hypo- or hyperthermia, pain, changes in organ perfusion, disturbances of the osmolarity, inflammatory- or immune- response create exceptional milieu and environment for the research.

In this chapter we reviewed main concepts of stress response in such environment additionally presenting some results of own research. It focuses on patients who had strong stressors working in acute or chronic manner (desaturation, increased afterload, volume overload, circulatory insufficiency) with all related elements affecting the model in clinical environment.
