Inflammatory Response in Chronic Heart Failure

Inflammatory Response in Chronic Heart Failure:  For more than 200 years it has been known that the Heart can be the seat of infectious and inflammatory processes in its various anatomical components: pericardium, myocardium, endocardium and valves. But it was not if not at the beginning of the 90s of the recent past century, when it was shown for the first time that atheromatous plaque, a primary lesion of atherosclerosis, can present an inflammatory component from the histopathological point of view 37, 47, 48 .

 

Summary

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  • 1 HEART AND INFLAMMATION.
  • 2 HEART FAILURE AND CYTOKINES
  • 3 USE OF ANTICITOCIN DRUGS IN CHRONIC HEART FAILURE
  • 4 Source

HEART AND INFLAMMATION.

There are numerous publications in medical journals from various areas of medicine, both clinical and experimental, suggesting that so-called pro-inflammatory cytokines, especially Alpha Tumor Necrosis Factor (TNF-alpha), play a very important role. important in the pathogenesis of chronic heart failure.

TNF-alpha, believed to be produced only by cells of the immune system (particularly activated monocytes and macrophages), has also been found to be synthesized in insufficient heart myocardial cells (myocytes), but not normal.

In the laboratory, Heart models with pressure or volume overload are managed, which make the insufficient myocardium capable of synthesizing these Molecules, in particular TNF-alpha. For this reason they are also called stress-induced cytokines. These cytokines produce a marked decrease in myocardial inotropism, stimulate the synthesis of interstitial connective tissue, cause cardiomyopathy, and induce apoptosis, both in vivo and in vitro. The expression of specific receptors for these cytokines is elevated in chronic heart failure.

These first studies were done in coronary arteries . It was also discovered that during the evolutionary process of atherosclerosis there is a low-intensity chronic systemic inflammatory component 64, 68, 79, 90, 123, 124, 126. When this inflammatory process increases, it is capable of causing changes in the atheromatous plaque which increases their vulnerability, causing the rupture, which is largely the culprit, of acute coronary syndromes 79, 90, 123, 124, 125. This low intensity inflammatory process is evident when it is found that Reactive Protein C (PCR ), which is a sensitive marker of inflammation, is moderately elevated, being an important percussor of an acute coronary event, when its serum levels increase 95, 105, 121, 122.

In these investigations, the sensitized PCR was used. For many years it was believed that the development of atheromatous plaque was strictly a degenerative process whose causative agents were the already known coronary risk factors. Never before was it thought that there was an inflammatory component in its genesis. To the even greater surprise of the medical community, various microorganisms such as Helicobacter pylori, Chlamidia pneumoniae, cytomegalovirus, and members of the herpes virus group were found to have some role in the development of atheromatous plaque. This fact raises the question that a certain group of antibiotics, especially last-generation macrolides (azithromycin), may be of some use in the treatment of acute coronary syndromes.

It is not the objective of this review to scrutinize the evidence in this regard. Also in the early 90s of the last century, it was suspected that inflammatory components could exist in chronic heart failure . With this thought, Pye et al. 21 in a clinical research study in patients with chronic heart failure, found high serum levels of CRP and that there was a relationship between the severity of the condition and the figures for this marker of inflammation.

HEART FAILURE AND CYTOKINES

In 1975 , Carswell and Cols. 1 discovered tumor necrosis factor-alpha (TNF-alpha), finding in Mice that had been injected with endotoxin, a compound that, when injected into other rodents affected by a certain tumor line, caused tumor necrosis. Hence the name of FNT with which it was called. This compound turned out to be a cytokine with multiple biological activities. Cytokines, which play a very important role in the immunologically induced inflammatory response, are very small (15 to 30 kDa) biomolecules, protein in nature. They are secreted by cells belonging to the immune system, mainly monocytes and active macrophages, in response to various inducing stimuli, including those caused by microorganisms 9, 10, 15, 20.

PROGRESSION OF CHRONIC HEART FAILURE

It has been observed that for several years heart failure remained more or less stable controlled with the classic digital and diuretic therapeutic scheme, but that suddenly and without apparent cause, there was a deterioration in the hemodynamic condition that quickly led to the patient. to death, either due to mechanical failure or malignant arrhythmia 75, 101, 126.

This progression of the disease is associated with a clear increase in the activity of the neuro-endocrine axis, particularly an increase in the serum levels of angiotensin II, norepinephrine and Endothelin-1 (E-1), as well as an increase in activity. of arginine vasopressin (antidiuretic hormone) 58, 75, 101, 103, 106. The suspicion that the increase in serum levels of these hormones was closely related to the deterioration of chronic heart failure was confirmed when treating these patients with inhibitors of the converting enzyme or convertase (ACEI’s) and beta-adrenergic blockers, a notable improvement in clinical symptoms was observed, also reducing the morbidity and mortality of the disease 31, 39, 86, 94, 96, 112, 113, 114, 118. Many works in this regard,Both experimental and clinical, were carried out in several countries.

The increasing availability of neuro-hormonal antagonist drugs has transformed the therapy of heart failure from a basically palliative (digital / diuretic) scheme to one that modifies the evolution of the disease 75. But that was not the whole story: it was thought that there was other chemical factors that could explain this deterioration in myocardial function, and the possibility began to be explored that certain cardio-depressant bio-molecules, such as TNF-alpha, could also occur in chronic heart failure and accelerate clinical deterioration 27, 29, 36 , 42, 43, 52, 101,126.

Let us briefly review some mechanisms that act in the genesis of chronic heart failure in its terminal phase. Systemic vasoconstriction is an important compensatory mechanism in heart failure. This vasoconstrictor response depends on the integrity of the sympathoadrenal nervous system and the renin-angiotensin-aldosterone axis58. This mechanism causes significant endothelial dysfunction, demonstrated in numerous clinical and experimental studies, which is ultimately the major cause of vasoconstriction 24, 27, 30, 40, 43, 46, 58, 73, 76, 83, 100, 102, 106, 107. In addition to the alteration of endothelium-dependent vasodilation, the increased E-1 circulation seen in heart failure may also play an important role in such vasoconstriction.

USE OF ANTICITOCIN DRUGS IN CHRONIC HEART FAILURE

It has been widely documented that pro-inflammatory cytokines depress myocardial contractility and contribute to the significant endothelial dysfunction seen in chronic heart failure, thereby promoting disease progression (deterioration) (“cytokine hypothesis”). With this information, it is logical to suppose that if its activity is antagonized we can improve the hemodynamic condition of the heart and temporarily stop its progression.

Being this response of cytokines mediated in part by the immune system, what is understood by those in the field is proposed as the “immunomodulatory management” of the disease 97, 104, 111, 115, 116.

Studies on the use of angiotensin-converting enzyme inhibitors (ACEI’s) have shown that their use causes a decrease in TNF-alpha, probably because it favorably modifies the hemodynamic condition of patients, decreasing the mechanical stress factor ( stress-induced cytokines), although it is not ruled out that there may be an interrelation between neurohormones (norepinephrine, angiotensin) and pro-inflammatory cytokines, in particular TNF-alpha. By this or those mechanisms, we could say that ACE inhibitor drugs have a direct and / or indirect anticytokine effect.

 

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