Naslov
Immunomodulation in pediatric cardiology

Autori
Malčić, Ivan ; Kniewald, Hrvoje ; Jelušić, Marija ; Dilber, Daniel ; Mustapić, Željka ; Dorner, Sanja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Biotechnology and Immuno- Modulatory Drugs 2005, Abstract book / - , 2005

Skup
4th Croatian Scientific conference on Biotehnology with international participation

Mjesto i datum
Zagreb, Hrvatska, 02.2005

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
immunomodulation; pediatric cardiology

Sažetak
The awareness that immune-mediated mechanisms may play a pathogenetic role in many disorders in pediatric cardiology, makes immunomodulatory therapy increasingly important. The greatest reason for that is cogestive heart disease caused by myocarditis. Myocarditis is very often overcome innaparently, but it can appear in fulminant necrosis or as a chronic dilated cardiomiopathy. Both of forms are potentially life threatening to patients, especially the fulminant form which is leathal within a few days. Dilated cardiomyopathies caused by virus myocarditis it is possible to treat today by different immunomoduatory mechanisms. It is considered that immunodeficiency lies behind all complicated forms of myocarditis. The course of disease is most likely caused by disturbed balance between pro- and anti- inflammatory cytokins. Considerably increased TNF-alpha and IL1-betha in comparisson to IL-6 and IL-10 is found in the group of patients with dilated cardiomiopathy after myocaritis that develops decreasing of sistolic function of the left ventricle. Intravenous immunoglubulin as immunomodulator considerably increases the level of antiinflammatory interleukins, especially IL-10 and anti-IL-1. It seams that because of this the contractiliti of the left ventricle increase considerably in some patients. Therefore, besides the conventional medicamentous therapy (ACE- inhibitors, angiotenzin II-blocers, diuretics, beta-blocers, digoksin) immunoglobulin should be applied intravenously, without any fear od doing harm to the patiens we cannot help. The application of other immunomodulation drugs depends exclusively on the final outcome of the diagnostic algorithm in which the dilated cardiomyopathy, as a unique hemodinamic entity, can be caused by different intramyocardial processes: chronic persistent myocarditis with finding of viral RNA (which can be persistent or replicating viral RNA), chronic immunological myocarditis with deposition of immune complexes and without viral RNA (pozitive immunofluorescency with deposition of immune complexes) and chronic viral heart disease (live virus exists in the heart). Differential diagnosis between the presence or absence of replicated RNA is made using molekular-genetic analysis by RT-PCR (reverse- transcriptase polymerase chain reaction). Every algorithm of diagnostic flow in processing heart muscle bioptate should end with that analysis, but technical (and financial) difficulties exist on this field. Immunomodulation by steroids (kortizon) and citostatics (ciklosporin, azathioprin) could theoreticaly be applied in cases where there is neither alive virusa nor replicated RNA. This explains why it is stated in the literature that immunomodulated therapy using steroids and citostatics is used successfully in one group of patients while in the other group the condition can even worsen (because immunomodulators supress own defence of the patients that have active virus in their hearts). In this study we will show current attitudes towards immunomodulatory therapy of myocarditis and dilated cardiomiopathy based on our own research of bioptate material of childrens' hearts with dilated cardiomiopathy. The research was conducted with the attempt of using all available conservative methods in treating dilated cardiomyopathies prior to heart transplantation. Furthermore, in children with transplanted heart immunmomodulation drugs (steroids, citostastics) are used as well. Perioperativ application of steroids in prevention of postoperative sepsis in cogenital heart defects is very popular. The sepsis is caused by releasing of proinflamatory cytokins under the influence of transcription factor kappa B and the induction of complemment cascade. This state is life threatening complication that can be prevented by preoperative application of deksamethason (1 mg/kg). Steroids decrease the sinthesis all of inflammatry mediators. For removing of inflammatory mediators ultrafiltration is used a last 10 years. These measures prevent multiple organ failures and lethal outcome for the operated patient. Immunosupression is used in postpericardiotomic sindrome, protein losing enteropathy after Fontane operation (by-pass of the right ventricle) and some other conditions in pediatric cardiology.

Izvorni jezik
Engleski

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