Post-traumatic state of the myocardium during chronic heart failure in polytrauma patients

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Post-traumatic state of the myocardium during chronic heart failure in polytrauma patients

Lutska S.V., Kharkiv National Medical University

Introduction

Heart and vascular diseases continue to be the leading cause of death in all countries. Cardiac pathology seriously affects the course of other pathological processes, complicating diagnosis and disrupting reparation processes, which, in turn, reduces the effectiveness of treatment and can make it untimely.

Traumatism is also the main aspect of the most important medical and social problems in the world. In economically developed countries, injuries rank third after cancer and cardiovascular among the causes of death, with most of the deaths occurring in employable individuals. According to WHO, 12 million people are dying from injury per year in the world. In 70 % of cases, the leading cause of death is severe combined trauma [1]. A significant part of people among injured patients has a cardiac history. Thus, according to various sources, coronary heart disease, hypertension, arrhythmia, heart failure are found in 44-62% of victims in our country [2]. Industrial and domestic injuries, combined injuries occupy a significant part in the structure of road transport, among which polysystemic injury with the development of shock conditions, including patients with a provoked cardiovascular system, is characterized by a particularly severe course.

Currently, great progress has been made in the diagnosis and treatment of conditions associated with traumatic illness, but the scientific literature does not sufficiently reflect studies of the course of traumatic illness in combination with a cardiac history. That is why the optimization of intensive care in this category of patients is an urgent medical problem.

Contribution of the main material. A characteristic feature of post-traumatic injuries is that their effect has not additive, but synergistic properties, that is, the effects of each injury do not add up, but strengthen each other. Any disorder of any nature, especially acute, are affected a single system of the body. This is due to the principles of the organization of the selfregulation of organism, which cause damage to the not injured internal organs. The leading mechanisms for implementing this situation are most often hypercatecholonemy, activation of free- radical oxidation, endotoxicosis, DIC syndrome and, most importantly, hypoxia. It is the latter mechanism that must be taken into account when drawing up an intensive care program for critical conditions associated with polytraumatic injuries [3]. heart repair mortality

Multiple traumatic injuries inevitably cause systemic inflammatory response syndrome (SIRS), one of the links of which is the so-called oxidative stress. The reason for its development is uncontrolled chain reactions with the formation of free radicals, that is, molecules that have unpaired electrons in external orbitals, so that free radicals are extremely active chemically and are able to damage cellular structures. Oxidative stress disrupts the control of inflammatory reactions, one of the reasons for which is the formation of active oxygen and nitrogen intermediates. Free radicals trigger the synthesis of cytokines, and through them - inflammatory mediators and adhesion molecules that cause loss of function and death of cells, including T-cells of the immune system. Free radicals derived from oxygen (superoxide and hydroxyl) are considered as mediators of inflammation and markers of tissue destruction in inflammatory reactions. One of the most important pathogenetic links of oxidative stress is damage to the mitochondria, followed by the development of energy deficiency [4]. Another cause of oxidative stress is the imbalance of prooxidants and antioxidants in favor of the first, which supports and enhances the formation of free radicals, which particularly affects tissues with high energy consumption, as well as cell matrix. Oxidative stress is also associated with the activation of apoptosis and/or cell necrosis mechanisms, which leads to the formation of a necrotic nucleus, and this is a sign of uncontrollability of damage.

It is important that the SIRS, induced by polytrauma, leads to injury to intact organs and systems, including the myocardium. The pathogenesis of myocardial damage is associated with the effect of cytokines on its corresponding receptors [5].

Chronic heart failure (CHF) is accompanied by cardiomyocyte apoptosis. Cardiomyocyte apoptosis is induced by hypoxia, myocardial overload, cardiotoxins and oxidative stress. It is the overload of the myocardium, followed by its hypertrophy, that lead to an increase in the myocardial need for energy without the ability to adequately satisfy it, that is, an energy deficit develops, as a result of which the myocardium contractile capacity (MCC) decreases. Energy deficiency also disrupts the work of the respiratory chain, as a result of which active forms of oxygen are formed [6].

Chronic increase of any origin blood pressure also enhances the programmable death of cardiomyocytes, including oxidative stress. Arterial hypertension inevitably causes energy deficiency in cardiomyocytes, which contributes to the release of proapoptotic factors. Understanding the mechanisms of development of cardiomyocytes apoptosis is necessary to find methods for treating heart failure.

A commonly recognized marker of myocardial injury is elevated levels of troponin I. This indicator is highly correlated with mortality, although this injuries with traumatic injuries has not yet been studied enough [7]. Another important biochemical marker that reflects the state of the myocardium is the cerebral natriuretic peptide BNP. The presence of endocrine function in the heart has been proven for a long time. Initially, an atrial natriuretic peptide (ANP) was discovered, stimulating natriuresis during stretching the left atrium. Then a similar peptide was found in the brain (BNP), and then it turned out that it is produced in the heart, and its functions are much wider. Only ANP (in atriums) and BNP (in the ventricles) are produced from all the currently known natriuretic peptides (NUP) in the heart. NUP products increase with an increase in both diastolic stretching and systolic tension (growth of pre- and post-loading). Changes in pre- and post-loading affect the synthesis of NUP by means of endothelin 1, NO and angiotensin II. NUP synthesis is three-stage: preprohormone - prohormone - hormone, prohormones inactive sections remain after the end of synthesis, called NT-proANP and NT-proBNP. Their concentration is closely correlated with the concentration of active hormones [8].

The effects of NUP are divided into renal and cardiovascular. NUP affect the glomerulus and collected ducts of the kidneys, as a result of which dilated afferent and constricted efferent glomerular arterioles, which reduces the reabsorption of sodium in the collected ducts, and the volume of primary urine increases. Another renal effects of NUP is inhibition of synthesis in the kidneys of aldosterone, renin and angiotensin II. All these effects lead to increased excretion of water and sodium, which, of course, reduces the circulating blood volume (CBV).

In addition to inhibition of sympathoadrenal and reninangiotensin systems, NUP directly affects the vascular system, reducing the tone of the main arteries and veins and increasing the microcirculation vessels permeability. This decreases blood pressure (BP) and venous return [9].

As shown by the above study of the literary sources, polytraumatic injury is accompanied by oxidative stress and energy deficiency, which affects the non-traumatic organs, including the myocardium.

The most important function of the heart is to ensure the movement of blood through the vessels for delivering oxygen to the tissues. This function is determined by three components: the myocardium contractile ability (MCA), preloading and post-loading. The level of preload and post-loading is determined by the correspondence degree of blood vessels volume and circulating blood. The leading factor of all components is MCA, the implementation of which is an increase in the number of connections between actin and myosin during stretching cardiomyocyte [10].

Post-loading is a tension of the ventricle during systole, which creates pressure in the pulmonary artery or in the aorta. Thus, the myocardium, like any pump, creates a pressure difference at the "input" (vena cava) and at the "output" (aorta). Within a decrease in MCA, the pressure difference decreases, most often there is a pressure increase "at the entrance" (central venous pressure - CVP) and a pressure decrease "at the exit" (blood pressure - BP) [11].

The pumping function of the heart includes systolic and diastolic components. Both components are energy dependent, and if the energy dependence of the systolic component can be explained clearly physically, then the needs for energy expenditure to relax the myocardium is associated with the need to remove calcium from the cytoplasm to the endoplasmic reticulum of cardiomyocyte [12]. Thus, the myocardium during all phases of its activity must constantly consume energy, even in the isometric voltage phase, when no useful work is carried out.

Volumetric blood flow rate, which is cardiac output (CO) reflects the speed of oxygen transport, that is, energy to tissues, which is why CO is considered the main indicator of circulatory function. At the same time, MCA provides sufficient oxygen transport during at least 0.28 Ht and hemoglobin concentrations is not less than 90 g/l [13]. However, the same CO can be provided during different levels of blood pressure and general peripheral vascular resistance (GPVR), and a pressure increase during a constant CO means a directly proportional increase in myocardial energy consumption. Thus, the myocardium, providing the tissue with energy, needs it itself, so it is necessary to assess the ratio of energy consumption of the myocardium with the energy supply of tissues. In this regard, such an indicator as blood flow power (BFP) has importance, which shows the rate of expenditure of useful energy that the myocardium can provide for maintain blood flow. The efficiency of the energy tissues supply by the circulatory system can be assessed by such indicators as the power tissues consumed (PTC) and oxygen reserve (OR), while the OR reflects the energy supply adequacy of tissues for their needs. The integral energy indicator of blood circulation is the circulatory reserve (CR), which is the product of blood flow power (BFP) and OR. A CR decrease always means the presence of circulatory failure of one or another genesis, and its increase means adequate satisfaction of the increased tissues needs in energy. During chronic heart failure, grade 1-2A HF and ejection fraction (EF) below 40% of the CR may decrease to 152±66 mWt/² [14].

During a CO decrease of any genesis, a vasoconstrictor reaction occurs. The mechanism of implementation of this reaction is associated with the activation of the sympathoadrenal system (SAS) as a reaction to stress caused by circulatory hypoxia. The physiological meaning of this reaction is to restore the correspondence between the volume of blood vessels and the volume of blood that locates in them. This reaction is absent only during vascular insufficiency, in which it is the first vasoconstrictor reaction that is blocked, and then the conditions for blood circulation deteriorate sharply. However, vasoconstriction nevertheless increases GPVR by optimizing blood flow conditions, the myocardium forces to create higher pressure for overcoming them, so to increase systolic tension, which, of course, increases the myocardium energy consumption. If the myocardium is able to convert the chemical energy of nutrient substrates into mechanical energy at a sufficient speed, which requires adequate blood circulation in the myocardium, severe heart failure does not develop, but if the cause of circulatory failure is heart failure, then there is an imbalance between the increased need for myocardium in energy and the ability to provide this need. A vicious cycle develops: heart failure triggers vasoconstriction, which imposes increased energy requirements on the myocardium, that is unable to be completely satisfied. The degree of such imbalance causes one or another degree of heart failure [15]. Thus, one of the possible directions of intensive care of this condition is the restoration of chemical energy faster transfer possibility into mechanical energy in the myocardium by overcoming oxidative stress.

According to literature data, inflammatory response and oxidative stress reduce the antioxidant capacity of cells, including cardiomyocytes. It is natural to hope that the use of antioxidant drugs will significantly increase the effectiveness of the disease treatment in which there is a pronounced and poorly managed inflammatory reaction [16]. At present, an important class of drugs has been created that can optimize the metabolism of cardiomyocytes and even restore hibernated myocardium, reducing the level of oxidative stress. One of this class groups include metabolitotropic medicines, including antioxidant drugs.

These drugs prevent the development of irreversible processes in the myocardium. Antioxidants are powerful absorbers of free radicals.

One of these drugs is ethylmethylhydroxypyridine succinate (EMGPS), the effects of which have been studied by many researchers. Their work convincingly shows that the use of EMGPS reliably increases MC during chronic heart failure. It is proved that EMGPS facilitates the experience of hypoxia by the cell. The effects of EMGPS are not organospecyphic, it has a beneficial effect on both neurocytes and cardiomyocytes, kidney, liver, intestines and lung cells. Antioxidants, including EMGPS, inhibit apoptosis in cardiomyocytes [17].

Conclusions

The analysis of available literary data made it possible to identify the following. The disease of the circulatory system, mainly the myocardium, does not lose the first place among the causes of death of the world's population. Similarly, the third place among the causes of death is preserved by traumatic injuries. According to the long-known laws of mathematical statistics, it follows a high probability of obtaining polytraumatic damage by persons with chronic heart failure, and even if the myocardium is not directly injured, it is damaged secondarily, resulting in an unfavorable combination of acute hypovolemia, CHF and secondary myocardium injury.

So far as both hypovolemia and CHF are variants of circulatory insufficiency, they aggravate each other, and the result is the development of a general energy deficit, including in the myocardium. An inevitable consequence of this is a decrease in MC, which only during the absence of vascular insufficiency causes inevitable consequence - a vasoconstrictor reaction, which imposes on the myocardium increased requirements for the energy consumption rate, which it is unable to fully fulfill. The result, therefore, depends on the ratio of the myocardium energy reserves and the severity degree of the compensatory vasoconstrictor reaction.

This is the situation that occurs within acute hypovolemia due to polytrauma during CHF. Naturally, in this case, based on the main links of pathogenesis described above, try to influence on the rate of substrates chemical energy transfer into the mechanical energy of myocardial contractions. One of the possible ways to increase this rate is to use metabolotropic antioxidant drugs, one of which is EMGPS.

During the intensive care of circulatory insufficiency, especially with the combination of CHF and acute hypovolemia, the control of the circulatory system and its energy plays an important role.

In accordance with the goal, we have chosen the following methods: those confirming the absence of acute traumatic or any other myocardial injury - determining the TnI concentration, confirming the CHF presence - determining the NT-proBNP concentration, controlling the energy efficiency of blood circulation - energy indicators determination. Blood circulation regulation, like any other function, is extremely multi-lane, so the study of individual indicators is often unproductive, and energy indicators are integral and easy to determine.

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