doktorska dizertacija [!]
Nikola Lakič (Avtor), Matjaž Bunc (Mentor), Ivan Krajnc (Član komisije za zagovor), Vojko Flis (Komentor)

Povzetek

Izhodišča: Nevrološki zapleti po operacijah na odprtem srcu predstavljajo pomemben zdravstveni in denarni problem. Povečujejo obolevnost, umrljivost in podaljšujejo hospitalizacijo sicer uspešno operiranih srčnih bolnikov. Spekter kliničnih manifestacij nevroloških pooperativnih sprememb je raznolik, od kognitivnih motenj, ki so najpogostejše, tranzitornih ishemičnih atak, delirantnih stanj, pa vse do polno razvitih možganskih kapi. Najpogosteje gre za cerebralno embolizacijo ali pa hipoperfuzijo skupaj z ishemično/reperfuzijsko poškodbo. Zaradi naraščanja povprečne starosti operiranih bolnikov, narašča tudi verjetnost omenjenih zapletov. Hipoteze: Znanstveni dokazi, da eritropoetin (EPO) deluje kot multipotentni tkivni protektivni dejavnik, tako v srcu kot v centralnem in perifernem živčnem sistemu, odpirajo nove možnosti zdravljenja in zaščite bolnikov pred ishemičnimi nevrološkimi dogodki. Perioperativna intravenozna aplikacija humanega rekombinantnega eritropoetina (rHuEpo) pri bolnikih, operiranih na odprtem srcu z zunajtelesnim krvnim obtokom, naj bi zmanjšala nastanek prehodnih ali trajnih okvar centralnega živčevja, zmanjšala medoperativno in pooperativno okvaro srčne mišice ter pooperativno okvaro ledvic. Terapija z rHuEpo naj bi prav tako zaščitila bolnike pred posledicami akutnih pooperativnih embolij. Cilj naše raziskave je bil preveriti, ali eritropoetin deluje kot zaščitni dejavnik možganskega, srčnega in ledvičnega tkiva, pri bolnikih po operaciji na odprtem srcu, hkrati pa prepoznati kateri so tisti dejavniki, ki lahko napovedo nove ishemične zaplete. Metode: V pričujočo raziskavo smo vključili 40 bolnikov, ki so bili predvideni za revaskularizacijsko operacijo na odprtem srcu z uporabo zunajtelesega obtoka krvi. Skupini 20 bolnikov, operiranih na srcu, smo perioperativno intravenozno aplicirali 3 odmerke rHuEpo (24.000 IU) in nato ocenili tveganje za pojav neželenih nevroloških zapletov ter ishemičnih poškodb ledvic in srca. 20 bolnikom v kontrolni skupini smo aplicirali placebo. Za določitev novih nevroloških zapletov smo na vseh udeležencih izvedli magnetno resonanco možgan (MRI) in izmerili koncentracijo protiteles za N-metil-D-aspartatne (NMDA) receptorje (NR2Ab), koncentracijo nevronsko specifičnih enolaz (NSE) in serumskega S100B. Za detekcijo ishemije na srcu in ledvicah smo biokemično določili koncentracijo laktata, troponina I, kreatin kinaze-srčna frakcija (CK-MB) in kreatinina. Rezultati: Pri skupini 20 kontrolnih bolnikov, ki niso prejeli rHuEpo, smo s pomočjo MRI pri 5 (25,0 %) bolnikih dokazali nove ishemične zaplete na možganih. Bolniki z dodatkom rHuEpo niso pokazali novih pooperativnih ishemičnih sprememb. Razlika med skupinama je bila statistično značilna (p=0,021). Statističnih razlik med parametri ishemije (NMDA, CK-MB, troponin I, laktat, NSE, S100B) nismo dokazali (p>0,05), so pa bile vrednosti v skupini bolnikov s prejetim rHuEpo bistveno nižje, kot pri bolnikih, ki so prejeli placebo. Izmed vseh testiranih parametrov so visoke vrednosti laktata pred (p=0,022) in po popustitvi stiskalke (p=0,048), ter trajanju samega operativnega posega (p=0,009) lahko statistično napovedali nove pooperativne ishemične zaplete. Zaključek: Dokazali smo, da dodatek rHuEpo pomembno zmanjša tveganje za razvoj novih ishemičnih zapletov na možganih pri bolnikih operanih na odprtem srcu detektiranih z MRI. Hkrati se je aplikacija rHuEpo iskazala kot varna za bolnike in lahko klinično služi kot zaščita pred novimi ishemičnimi spremembami tkiv po operacijah na odprtem srcu.

Ključne besede

zunajtelesni krvni obtok;rekombinantni humani eritropoetin;centralni živčni sistem;ledvice;srce;ishemija;perioperacijska zaščita;

Podatki

Jezik: Slovenski jezik
Leto izida:
Tipologija: 2.08 - Doktorska disertacija
Organizacija: UM MF - Medicinska fakulteta
Založnik: N. Lakič]
UDK: 616.12-089-06(043.3)
COBISS: 290146816 Povezava se bo odprla v novem oknu
Št. ogledov: 1218
Št. prenosov: 107
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Angleški jezik
Sekundarni naslov: Protection of central nervous system, kidneys, and heart with erythropoetin during open heart surgery
Sekundarni povzetek: ABSTRACT PERIOPERATIVE PROTECTION OF CENTRAL NERVOUS SYSTEM, KIDNEYS AND HEARTH WITH ERYTRHOPOETIN DURING OPEN HEART SURGERY Objectives: Neurological complications, following open heart surgery, are important medical and financial problem. They increase morbidity, mortality and prolong hospitalization of otherwise successfully operated cardiac patients. Spectrum of clinical postoperative neurological manifestations vary from cognitive disorders which are most common, delirious conditions, transient ischemic attacks, all the way to fully developed stroke. Cerebral embolization, hypoperfusion, together with ischemic/reperfusion injury, are the most common conditions. Increasing average age of operated patients, who undergo such surgeries, increases the likelihood of complications. Hypothesis: According to scientific evidences erythropoietin (EPO) acts as a tissue protective factor in the heart as well as in the central and peripheral nervous system. This opens up new opportunities for treatment and protection of patients against new ischemic neurological events. Perioperative intravenous administration of recombinant human erythropoietin (rHuEpo) in patients with opened heart surgery and with external blood circulation should reduce the formation of transient or permanent brain damage, it should decrease periopeartive and postoperative impairments of cardiac muscle, and also decrease postoperative renal insufficiency. Therapy with rHuEpo should also protect the patients against the occurrence of acute postoperative complications such as embolisms. The aim of our study was to examine whether perioperative application of rHuEpo may actually act as a protective factor for brain, heart ,and kidney tissue in patients who underwent opened heart surgery with extracorporeal circulation and simultaneously identify which were the factors that could predict new ischemic complications. Methods: In the present study 40 patients who were scheduled for revascularization heart surgery using external blood circulation were included. 20 patients received 3 intravenous doses of rHuEpo (24,000 IU) and the risk of adverse neurological complications, ischemic damage of kidneys and heart was assesed. 20 patients in the control group received placebo. Magnetic resonance imaging (MRI) to detect brain ischemic lesions was performed. Additionally, the concentration of antibodies for N-methyl-D-aspartate (NMDA) receptors (NR2Ab), neuron-specific enolase (NSE), and serum S100B to identify new neurological complications were determined. Furthermore, serum concentration of lactate, troponin I, creatin kinase heart fraction CK-MB, and creatinine for the detection of ischemia in heart tissue and kidneys were measured. Results: Patients who received rHuEpo showed no new postoperative ischemic changes in the brain. In the control group 5 out of 20 (25,0 %) patients new ischemic lesions MRI lesions were detected. The difference was statistically significant (p=0.021). Statistical differences for parameters of ischemia (NMDA, CK-MB, troponin I, lactate, NSE, S100B) could not be proved between the tested groups (p>0.05). However, the values were considerably lower in the group of patients who received rHuEpo compared to the patients who received placebo. Among all tested parameters high levels of lactate before (p=0.022) and after releasing the aortic clamp (p=0.048) and duration of surgerical procedure (p=0.009) could predict new postoperative ischemic complications. Conclusions: MRI imaging has proven that the addition of rHuEpo significantly reduce the risk of developing new ischemic complications in the brain tissue of patients after open heart surgery. Application of rHuEpo showed to be safe for the patients and may clinically serve as tissue protection agent against new postoperative ischemic changes.
Sekundarne ključne besede: Operacija na odprtem srcu;Disertacije;Komplikacije;Preprečevanje;Eritropoetin;
URN: URN:SI:UM:
Vrsta dela (COBISS): Doktorska disertacija
Komentar na gradivo: Univ. v Mariboru, Medicinska fak.
Strani: 3 f., 118 str.
ID: 9226663